30 results on '"S. Pel"'
Search Results
2. PO.7.144 ASSESSLE- a new tool to assess sle disease activity- the patients’ perspective
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D Paran, M Ben-Am, L Mendel, P Ari, V Furer, O Elalouf, J Wollman, T Eviatar, S Pel, S Kivity, O Elkayam, and N Agmon-Levin
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- 2022
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3. Collectivity at the prolate-oblate transition: The 21+ lifetime of 190W
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E. Şahin, V. Werner, A.K. Mistry, M. Rudigier, K. Nomura, J. Jolie, N. Pietralla, P.H. Regan, G. Ağgez, H.M. Albers, U. Ahmed, Ö. Aktaş, A. Algora, S. Alhomaidhi, C. Appleton, T. Arıcı, M. Armstrong, A. Banerjee, J. Benito, G. Benzoni, A. Blazhev, P. Boutachkov, A.M. Bruce, B. Cederwall, M.M.R. Chishti, M.L. Cortés, F. Crespi, B. Das, T. Davinson, T. Dickel, M. Doncel, A. Ertoprak, A. Esmaylzadeh, L.M. Fraile, E.R. Gamba, J. Gerl, M. Górska, J. Ha, E. Haettner, O. Hall, H. Heggen, C. Hornung, N. Hubbard, S. Jazrawi, P.R. John, C.E. Jones, V. Karayonchev, E. Kazantseva, R. Kern, L. Knafla, I. Kojouharov, P. Koseoglou, G. Kosir, D. Kostyleva, N. Kurz, N. Kuzminchuk, M. Llanos-Expósito, R. Lozeva, D. Mengoni, T.J. Mertzimekis, M. Mikolajczuk, A.I. Morales, I. Mukha, J.R. Murias, B.S. Nara-Singh, S.E.A. Orrigo, J. Pellumaj, S. Pelonis, S. Pietri, S. Pigliapoco, Zs. Podolyák, M. Polettini, K. Rezynkina, H.A. Rösch, H. Schaffner, Ch. Scheidenberger, L. Sexton, P.-A. Söderström, Y.K. Tanaka, J.J. Valiente-Dobón, P. Vasileiou, J. Vasiljević, J. Vesic, H. Weick, J. Wiederhold, A. Yaneva, G. Zhang, J. Zhao, and A. Zyriliou
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Nuclear structure ,γ-ray spectroscopy ,Isomer spectroscopy ,Shape phase transition ,DESPEC ,NUSTAR ,Physics ,QC1-999 - Abstract
The neutron-rich rare isotope 190W is discussed as a candidate for a prolate-oblate transitional nucleus with maximum γ-softness. The collectivity of this isotope is assessed for the first time by the measurement of the reduced E2 transition probability of its first 2+ state to the ground state. The experiment employed the FAst TIming Array (FATIMA), comprised of 36 LaBr3(Ce) scintillators, which was part of the DESPEC setup at GSI, Darmstadt. The 41+ and 21+ states of 190W were populated subsequently to the decay of its 127(12) μs isomeric Jπ=10− state. The mean lifetime of the 21+ state was determined to be τ=274(28) ps, which corresponds to a B(E2;21+→01+) value of 95(10) W.u. The results motivated a revision of previous calculations within an energy-density functional-based interacting boson model-2 approach, yielding E2 transition properties and spectroscopic quadrupole moments for tungsten isotopes. From comparison to theory, the new data suggest that 190W is at the transition from prolate to oblate structure along the W isotopic chain, which had previously been discussed as a nuclear shape-phase transition.
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- 2024
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4. OP0177 IMMUNOGENICITY INDUCED BY TWO AND THREE DOSES OF THE BNT162B2 mRNA VACCINE IN PATIENTS WITH AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES AND IMMUNOCOMPETENT CONTROLS: A LONGITUDINAL MULTI-CENTER STUDY
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V. Furer, T. Eviatar, H. Peleg, D. Hagin, T. Freund, D. Levartovsky, D. Paran, I. Kaufman, A. Broyde, A. Polachek, O. Elalouf, J. Feld, A. Haddad, T. Gazitt, M. Elias, N. Hijaze, F. Kharouf, S. Gertel, S. Nevo, S. Pel, D. Zisman, and O. Elkayam
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Rheumatology ,Immunology ,Immunology and Allergy ,General Biochemistry, Genetics and Molecular Biology - Abstract
BackgroundData on the kinetics of the immune response to SARS-CoV-2 vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited.ObjectivesTo evaluate the kinetics of the immune response induced by two and three doses of the BNT162b2 mRNA vaccine in adult patients with AIIRD and immunocompetent controls.MethodsA prospective multicenter study investigated the antibody response to the BNT162b2 vaccine by serial measurement of serum anti-SARS-CoV-2 S1/S2 IgG titers at the following time points: 2-6 weeks (AIIRD n=720, controls n=122) and six months (AIIRD n=628, controls=116) after the second vaccine dose, and 2-6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). A seropositive response was defined as a detectable anti-S1/S2 IgG titer ≥ 15 BAU/ml. T-cell immune response was evaluated in a sample of patients (n=28) and controls (n=9) by intracellular staining of S-stimulated CD4+ T-cells for TNFα and IFNγ production.ResultsThe two-dose vaccine regimen induced a higher humoral response in controls compared to patients, as reflected by the post-vaccination seropositivity rates of 100% vs 84.72%, prd vaccine, the seropositivity rate increased to 80.47% and 100% in AIIRD and control groups, p=0.0028, with a significantly higher increase of S1/S2 IgG titers in controls compared with AIIRD patients, 284.09±76.58 vs 219.39±151.55 BAU/ml, p=0.0016. At all-time points, S1/S2 IgG titers were significantly lower in AIIRD patients compared with controls (Figure 1).We further investigated the impact of therapies on the vaccine‘s immunogenicity (Figure 1). Glucocorticoids (GC) were associated with a significantly lower seropositivity rate and lower S1/S2 IgG titers compared to controls at all time points. Monotherapy with methotrexate (MTX) was associated with a comparable to controls humoral response at all time points. Anti-cytokine biologics (TNFi, IL6i, IL17i) were associated with an initial high seropositivity rate, similar to controls, followed by a steeper decline at 6 months, 79.82% vs 96.55%, p=0.0001, and restoration of seropositivity after the 3rd vaccine dose in all patients. JAKi were associated with a mildly decreased seropositivity rate after the 2nd vaccine dose and similar to controls response after the 3rd vaccine dose. Abatacept was associated with a reduced immunogenicity after the 2nd vaccine dose, but was restored to 100% seropositivity after the 3rd vaccine dose. Rituximab (RTX) significantly blunted the humoral response at all time points, with a seropositivity rate of 42% after the 2nd vaccine dose, 29% at 6 months, and with increase to 40% after the 3rd vaccine dose. A third of the RTX-treated patients who were seronegative after two vaccine doses, seroconverted after the 3rd dose. The multivariate model for predicting the seropositive response to vaccination found that higher S1/S2 IgG titers after the 2nd vaccine dose was associated with a higher seropositivity rate following the 3rd vaccine dose, OR 1.026 (1.008-1.045), p=0.0027, and that treatment with RTX was associated with a 14.3-fold risk for a negative humoral response, p≤0.0001. Cellular immune response, evaluated mainly in RTX treated patients, was preserved prior to and after the 3rd vaccine dose and was similar to controls.ConclusionOver a six-month period, the two dose BNTb262 vaccination was associated with a similar extent of waning of the humoral immune response in AIIRD patients and controls. The 3rd vaccine dose restored the response in all controls and in patients treated with MTX monotherapy, anti-cytokine biologics, abatacept, and JAKi. Treatment with GC and RTX was associated with an impaired humoral response at all time points.AcknowledgementsWe would like to thank the statistician Mr Yishai Friedlander and Mr Yoram Neufeld for their valuable assistance.Disclosure of InterestsNone declared
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- 2022
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5. POS0258 SAFETY AND IMMUNOGENICITY OF BNT162b2 mRNA COVID-19 VACCINE AMONG ADOLESCENTS WITH RHEUMATIC DISEASES TREATED WITH IMMUNOMODULATORY MEDICATIONS
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M. Heshin-Bekenstein, A. Ziv, N. Toplak, D. Hagin, D. Kadishevich, Y. Butbul, E. Saiag, G. Shefer, O. Sharon, S. Pel, O. Elkayam, and Y. Uziel
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Rheumatology ,Immunology ,Immunology and Allergy ,General Biochemistry, Genetics and Molecular Biology - Abstract
BackgroundAdolescents with juvenile-onset autoimmune inflammatory rheumatic diseases (AIIRD) could be at risk for disease flare secondary to SARS-CoV-2 infection or to withholding anti-inflammatory therapy. While vaccination can protect against COVID-19, safety and immunogenicity data regarding anti-SARS-CoV-2 vaccines among adolescents with AIIRD are limited.ObjectivesThis international, prospective, multicentre study evaluated the safety and immunogenicity of the BNT162b2 anti-SARS-CoV-2 vaccine among adolescents and young adults with juvenile-onset AIIRD, 80% of whom are on chronic immunomodulatory therapy.MethodsVaccine side effects, disease activity, and short-term efficacy were evaluated after 3 months in 91 patients. Anti-spike S1/S2 IgG antibody levels were evaluated in 37 patients and 22 controls, 2–9 weeks after the second dose.ResultsNinety-one patients and 40 healthy controls were included. Safety profile was good, with 96.7% (n=88) of patients reporting mild or no side-effects, and no change in disease activity. However, 3 patients had transient acute symptoms: 2 following the first vaccination (renal failure and pulmonary haemorrhage) and 1 following the second dose (mild lupus flare vs. viral infection). Seropositivity rate was 97.3% in the AIIRD group compared with 100% among controls. However, anti-S1/S2 antibody titres were significantly lower in the AIIRD group compared with controls (242±136.4 vs. 387.8±57.3 BAU/ml, respectively; pConclusionVaccination of juvenile-onset AIIRD patients demonstrated good short-term safety and efficacy, high seropositivity rate, but lower anti-S1/S2 antibody titres compared to healthy controls. These results should encourage vaccination of adolescents with juvenile-onset AIIRD, even while on immunomodulation.References[1]Fact sheet for healthcare providers administrating vaccine emergency use authorization (EUA) of the Pfizer-BioNTech COVID-19 vaccine to prevent coronavirus disease 2019 (COVID-19) for 12 years of age and older dilute before use for 12 years of age and old; Available from: www.cvdvaccine.com.[2]Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Eng J Med 2020;383:2603–15. DOI: 10.1056/NEJMoa2034577[3]Frenck RW, Klein NP, Kitchin N, Gurtman A, Absalon J, Lockhart S, et al. Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. N Eng J Med 2021;385:239–50.[4]First COVID-19 vaccine approved for children aged 12 to 15 in EU | European Medicines Agency [Internet]. [cited 2022 Jan 3]. Available from: https://www.ema.europa.eu/en/news/first-covid-19-vaccine-approved-children-aged-12-15-eu[5]FDA authorizes Pfizer-BioNTech COVID-19 vaccine for emergency use in children 5 through 11 Years of Age | FDA [Internet]. [cited 2022 Jan 1]. Available from: https://www.fda.gov/news-events/press-announcements/fda-authorizes-pfizer-biontech-covid-19-vaccine-emergency-use-children-5-through-11-years-age[6]Woodworth KR, Moulia D, Collins JP, Hadler SC, Jones JM, Reddy SC, et al. The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine in Children Aged 5–11 Years — United States, November 2021. MMWR Morbidity and Mortality Weekly Report [Internet]. 2021 Nov 12 [cited 2021 Dec 1];70(45):1579–83. Available from: https://www.cdc.gov/mmwr/volumes/70/wr/mm7045e1.htm[7]Liguoro I, Pilotto C, Bonanni M, Ferrari ME, Pusiol A, Nocerino A, et al. SARS-COV-2 infection in children and newborns: a systematic review. Eur J Pediatr 2020;179:1029–46.AcknowledgementsWe thank the families and adolescents who participated in the study. We thank Mr. Yishai Friedlander, MPH, for performing the statistical analysis. We thank Faye Schreiber, MS, for editing the manuscript.Disclosure of InterestsNone declared
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- 2022
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6. POS1244 THE EFFECT OF SECUKINUMAB ON THE HUMORAL RESPONSE FOLLOWING TWO AND THREE DOSES OF THE BNT162b2 mRNA VACCINE IN PATIENTS WITH SPONDYLOARTHRITIS
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O. Elkayam, T. Eviatar, H. Peleg, D. Paran, D. Levartovsky, I. Kaufman, A. Broyde, O. Elalouf, A. Polachek, J. Feld, A. Haddad, T. Gazitt, M. Elias, N. Hijaze, M. Aassi, E. Quebe-Fehling, I. Alarcon, S. Pel, D. Zisman, and V. Furer
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Rheumatology ,Immunology ,Immunology and Allergy ,General Biochemistry, Genetics and Molecular Biology - Abstract
BackgroundData on the effect of secukinumab on the humoral response to the BNT162b2 mRNA vaccine are limited.ObjectivesWe aimed to assess prospectively the humoral response to the BNT162b2 mRNA vaccine in patients with spondyloarthritis (SpA) treated with secukinumab in comparison to immunocompetent controls.MethodsPatients with psoriatic arthritis (PsA) or ankylosing spondylitis (AS) treated with secukinumab for at least 3 months and immunocompetent controls were vaccinated with two-dose regimen of the BNT162b2 mRNA vaccine. Clinical and laboratory assessments were performed at 2-8 weeks [SpA: 37 on secukinumab, (median age 53% female), 122 controls (median age 53, 51% female)], and 6 months [SpA: 27 on secukinumab, 116 controls] after the second vaccine dose. A subgroup of patients (22 SpA on secukinumab, 45 controls) were evaluated after the third vaccine dose. The seropositive response was defined as a detectable S1/S2 IgG ≥15 binding antibody units (BAU)/ml.ResultsThe two-dose vaccine regimen induced a similar immunogenic response in patients and controls reflected by the seropositivity rates of 100% in both groups. After six months, the rate of seropositivity remained as high as 96% in both secukinumab-treated patients and immunocompetent controls. The decline of S1/S2 IgG titer within six months was similar in controls and secukinumab-treated patients, -66.4 (95% CI {-70.9, -39.9}) and -55 BAU/ml (95% CI {-95.42, -36.87)). Following the third vaccine, the seropositivity rate increased to 100 % in both groups. At all-time points, S1/S2 IgG titers were similar in secukinumab treated patients and immunocompetent controls (Figure 1).Figure 1.Kinetics of an immunogenic response (S1/S2 IgG titer) to two and three doses of the BNT162b2 mRNA vaccine in SpA patients treated with secukinumab and immunocompetent controls.ConclusionSpA patients treated with secukinumab consistently demonstrated an adequate humoral response to the BNT162b2 mRNA vaccination similar to immunocompetent controls, both short-term and within six months after two vaccine doses and after the third vaccine dose.AcknowledgementsWe would like to thank Mr Yishai Friedlander and Mr Yoram Neufeld for their assistance.Disclosure of InterestsOri Elkayam: None declared, Tali Eviatar: None declared, Hagit Peleg: None declared, Daphna Paran: None declared, David Levartovsky: None declared, Ilana Kaufman: None declared, Adi Broyde: None declared, Ofir Elalouf: None declared, Ari Polachek: None declared, Joy Feld: None declared, Amir Haddad: None declared, Tal Gazitt: None declared, Muna Elias: None declared, Nizar Hijaze: None declared, Maher Aassi Employee of: Novartis Pharma AG, Erhard Quebe-Fehling Employee of: Novartis Pharma AG, Ivette Alarcon Employee of: Novartis Pharma AG, Sara Pel: None declared, Devy Zisman: None declared, Victoria Furer: None declared
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- 2022
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7. Complications of unintentional dural puncture during labour epidural analgesia: a 10-year retrospective observational study
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S. Poma, M. C. Bonomo, G. Gazzaniga, M. Pizzulli, A. De Silvestri, C. Baldi, F. Broglia, M. Ciceri, M. Fuardo, F. Morgante, S. Pellicori, E. M. Roldi, M. P. Delmonte, F. Mojoli, and A. Locatelli
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Labour analgesia ,Postdural puncture headache ,Unintentional dural puncture ,Neuraxial analgesia ,Labour complications ,Anesthesiology ,RD78.3-87.3 ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Introduction Unintentional dural puncture (UDP) occurs in 0.5–1.5% of labour epidural analgesia cases. To date, little is known about evidence of UDP-related complications. This work aimed to assess the incidence of intrapartum and postpartum complications in parturients who experienced UDP. Methods This is a 10-year retrospective observational study on parturients admitted to our centre who presented UDP. Data collection gathered UDP-related complications during labour and postpartum. All women who displayed UDP received medical therapy and bed rest. An epidural blood patch (EBP) was not used in this population. Once asymptomatic, patients were discharged from the hospital. Results Out of 7718 neuraxial analgesia cases, 97 cases of UDP occurred (1.25%). During labour, complications appeared in a small percentage of analgesia procedures performed, including total spinal anaesthesia (1.0%), extended motor block (3%), hypotension (4.1%), abnormal foetal heart rate (2%), inadequate analgesia (14.4%), and general anaesthesia following neuraxial anaesthesia failure (33.3% of emergency caesarean sections). During the postpartum period, 53.6% of parturients exhibited a postdural puncture headache, 13.4% showed neurological symptoms, and 14.4% required neurological consultation and neuroimaging. No patient developed subdural hematoma or cerebral venous sinus thrombosis; one woman presented posterior reversible encephalopathy syndrome associated with eclampsia. Overall, 82.5% of women experienced an extension of hospital stay. Conclusion Major complications occurred in a small percentage of patients during labour. However, since they represent high-risk maternal and neonatal health events, a dedicated anaesthesiologist and a trained obstetric team are essential. No major neurological complications were registered postpartum, and EBP was not performed. Nevertheless, all patients with UDP were carefully monitored and treated until complete recovery before discharge, leading to an extension of their hospitalization.
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- 2023
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8. A regional modelling study of halogen chemistry within a volcanic plume of Mt Etna's Christmas 2018 eruption
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H. Narivelo, P. D. Hamer, V. Marécal, L. Surl, T. Roberts, S. Pelletier, B. Josse, J. Guth, M. Bacles, S. Warnach, T. Wagner, S. Corradini, G. Salerno, and L. Guerrieri
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Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Volcanoes are known to be important emitters of atmospheric gases and aerosols, which for certain volcanoes can include halogen gases and in particular HBr. HBr emitted in this way can undergo rapid atmospheric oxidation chemistry (known as the bromine explosion) within the volcanic emission plume, leading to the production of bromine oxide (BrO) and ozone depletion. In this work, we present the results of a modelling study of a volcanic eruption from Mt Etna that occurred around Christmas 2018 and lasted 6 d. The aims of this study are to demonstrate and evaluate the ability of the regional 3D chemistry transport model Modèle de Chimie Atmosphérique de Grande Echelle (MOCAGE) to simulate the volcanic halogen chemistry in this case study, to analyse the variability of the chemical processes during the plume transport, and to quantify its impact on the composition of the troposphere at a regional scale over the Mediterranean basin. The comparison of the tropospheric SO2 and BrO columns from 25 to 30 December 2018 from the MOCAGE simulation with the columns derived from the TROPOspheric Monitoring Instrument (TROPOMI) satellite measurements shows a very good agreement for the transport of the plume and a good consistency for the concentrations if considering the uncertainties in the flux estimates and the TROPOMI columns. The analysis of the bromine species' partitioning and of the associated chemical reaction rates provides a detailed picture of the simulated bromine chemistry throughout the diurnal cycle and at different stages of the volcanic plume's evolution. The partitioning of the bromine species is modulated by the time evolution of the emissions during the 6 d of the eruption; by the meteorological conditions; and by the distance of the plume from the vent, which is equivalent to the time since the emission. As the plume travels further from the vent, the halogen source gas HBr becomes depleted, BrO production in the plume becomes less efficient, and ozone depletion (proceeding via the Br+O3 reaction followed by the BrO self-reaction) decreases. The depletion of HBr relative to the other prevalent hydracid HCl leads to a shift in the relative concentrations of the Br− and Cl− ions, which in turn leads to reduced production of Br2 relative to BrCl. The MOCAGE simulations show a regional impact of the volcanic eruption on the oxidants OH and O3 with a reduced burden of both gases that is caused by the chemistry in the volcanic plume. This reduction in atmospheric oxidation capacity results in a reduced CH4 burden. Finally, sensitivity tests on the composition of the emissions carried out in this work show that the production of BrO is higher when the volcanic emissions of sulfate aerosols are increased but occurs very slowly when no sulfate and Br radicals are assumed to be in the emissions. Both sensitivity tests highlight a significant impact on the oxidants in the troposphere at the regional scale of these assumptions. All the results of this modelling study, in particular the rapid formation of BrO, which leads to a significant loss of tropospheric ozone, are consistent with previous studies carried out on the modelling of volcanic halogens.
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- 2023
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9. The effect of attendance in the Dutch breast cancer screening program on breast tumor characteristics among migrant women
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R.R.E. Dassen, S. Pelders, L. de Munck, A. Jager, M.J. Hooning, J.H. van Dam, and B.A.M. Heemskerk-Gerritsen
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Breast cancer ,Screening ,Migrants ,Tumor characteristics ,Incidence ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: In general, migrant women have a lower breast cancer (BC) incidence rate and higher BC mortality than autochthonous women. Further, migrant women show lower participation in the national BC screening program. To further investigate those aspects, we aimed to determine differences in incidence and tumor characteristics between autochthonous and migrant BC patients in Rotterdam, the Netherlands. Methods: We selected women diagnosed with BC in Rotterdam during 2012–2015 from the Netherlands Cancer Registry. Incidence rates were calculated by migrant status (i.e., women with or without migration background). Multivariable analyses revealed adjusted odds ratios (OR) and 95% confidence intervals (CI) on the association between migration status and patient and tumor characteristics, additionally stratified by screening attendance (yes/no). Results: In total 1372 autochthonous and 450 migrant BC patients were included for analysis. BC incidence was lower among migrants than among autochthonous women. Overall, migrant women were younger at BC diagnosis (53 vs. 64 years, p
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- 2023
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10. Recent progress of JT-60SA project toward plasma operation
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H. Shirai, K. Takahashi, E. Di Pietro, D. Abate, W. Abdel Maksoud, H. Abe, N. Aiba, T. Abe, M. Akimitsu, J. Ayllon-Guerola, T. Arai, J.-F. Artaud, N. Asakura, N. Ashikawa, L. Balbinot, P. Barabaschi, O. Baulaigue, E. Belonohy, A. Belpane, W. Bin, F. Bombarda, T. Bolzonella, F. Bonne, M. Bonotto, J. Botija, J. Buermans, S. Cabrera-Pérez, A. Cardella, D. Carralero, L. Carraro, J. Cavalier, M. Cavinato, M. Chernyshova, S. Chiba, S. Clement-Lorenzo, V. Cocilovo, S. Coda, R. Coelho, I. Coffey, B. Collin, V. Corato, A. Cucchiaro, T. Czarski, M. Dairaku, S. Davis, C. Day, E. Dela Luna, G. De Tommasi, P. Decool, L. Di Pace, M. Dibon, G. Disset, F. D’Lsa, A. Ejiri, Y. Endo, N. Ezumi, G. Falchetto, A. Fassina, P. Fejoz, A. Ferro, W. Fietz, L. Figini, T. Fornal, G. Frello, T. Fujita, T. Fukuda, K. Fukui, M. Fukumoto, H. Funaba, M. Furukawa, S. Futatani, L. Gabellieri, E. Gaio, K. Galazka, J. Garcia, J. Garcia-Dominguez, J. Garcia-Lopez, M. Garcia-Munoz, L. Garzotti, F. Gasparini, S. Gharafi, L. Giacomelli, G. Ginoulhiac, G. Giruzzi, L. Giudicotti, J. Gonzalez-Martin, R. Guillén-González, N. Hajnal, S. Hall, K. Hamada, K. Hanada, M. Hanada, K. Hasegawa, S. Hatakeyama, V. Hauer, N. Hayashi, T. Hayashi, R. Heller, J. Hidalgo-Salaverri, S. Higashijima, J. Hinata, S. Hiranai, J. Hiratsuka, R. Hiwatari, C. Hoa, H. Homma, A. Honda, M. Honda, K. Hoshino, H. Hurzlmeier, M. Iafrati, K. Ibano, H. Ichige, M. Ichikawa, M. Ichimura, K. Ida, S. Ide, H. Idei, M. Iguchi, T. Iijima, S. Iio, R. Ikeda, Y. Ikeda, T. Imai, R. Imazawa, S. Inagaki, M. Inomoto, S. Inoue, A. Isayama, S. Ishida, Y. Ishii, M. Isobe, F. Janky, E. Joffrin, A. Jokinen, S. Kado, S. Kajita, K. Kajiwara, Y. Kamada, I. Kamata, A. Kaminaga, K. Kamiya, D. Kanapienyte, Y. Kashiwa, M. Kashiwagi, K. Katayama, Y. Kawamata, G. Kawamura, K. Kawano, Y. Kazakov, K. Kimura, F. Kin, M. Kisaki, S. Kitajima, K. Kiyono, K. Kizu, Y. Ko, K. Kobayashi, M. Kobayashi, S. Kobayashi, Ta. Kobayashi, To. Kobayashi, G. Kocsis, A. Kojima, S. Kokusen, M. Komata, K. Komuro, S. Konishi, A. Kovacsik, I. Ksiazek, M. Kubkowska, G. Kühner, M. Kuramochi, K. Kurihara, T. Kurki-Suonio, A.B. Kurniawan, T. Kuwata, B. Lacroix, V. Lamaison, A. Lampasi, P. Lang, P. Lauber, K. Lawson, Q. LeCoz, A. Louzguiti, R. Maekawa, T. Maekawa, S. Maeyama, G. Maffia, P. Maget, J. Mailloux, I. Maione, A. Maistrello, K. Malinowski, A. Mancini, G. Marchiori, J.-L. Marechal, V. Massaut, S. Masuzaki, R. Matoike, G. Matsunaga, S. Matsunaga, A. Matsuyama, Ch Mayri, M. Mattei, M. Medrano, A. Mele, I. Meyer, F. Michel, T. Minami, Y. Miyata, J. Miyazawa, Y. Miyo, T. Mizuuchi, K. Mogaki, J. Morales, P. Moreau, T. Morisaki, S. Morishima, S. Moriyama, A. Moro, H. Murakami, M. Murayama, S. Murakami, K. Nagasaki, O. Naito, N. Nakamura, S. Nakamura, T. Nakano, Y. Nakashima, V. Nardino, E. Narita, Y. Narushima, K. Natsume, S. Nemoto, R. Neu, S. Nicollet, M. Nishikawa, S. Nishimura, T. Nishitani, M. Nishiura, T. Nishiyama, M. Nocente, Y. Nobuta, L. Novello, F. Nunio, S. Ochoa, K. Ogawa, T. Ogawa, Y. Ogawa, S. Ohdachi, Y. Ohmori, N. Ohno, Y. Ohtani, K. Ohtsu, M. Ohzeki, T. Oishi, J. Okano, K. Okano, Y. Onishi, M. Osakabe, T. Oshima, V. Ostuni, A. Owada, M. Oya, Y. Oya, T. Ozeki, M.M. Parody Guzmán, R. Pasqualotto, S. Pelli, E. Perelli, E. Peretti, G. Phillips, C. Piccinni, L. Pigatto, A. Pironti, A. Pizzuto, B. Plöckl, G. Polli, J.-M. Poncet, P. Ponsot, G. Pucella, M. Puiatti, D. Radloff, V. Raimondi, F. Ramos, P. Rancsik, D. Ricci, S. Ricciarini, N. Richermoz, E. Rincon, A. Romano, P. Rossi, P. Roussel, G. Rubino, H. Saeki, A. Sagara, S. Sakakibara, H. Sakamoto, Miki Sakamoto, Mizu Sakamoto, Y. Sakamoto, A. Sakasai, S. Sakata, R. Sakurai, B. Salanon, A. Salmi, G. Sannazzaro, R. Sano, A. Sanpei, T. Sasajima, S. Sasaki, H. Sasao, F. Sato, M. Sato, T. Sato, M. Sawahata, A. Scherber, S. Scully, J. Segado-Fernandez, M. Seki, N. Seki, S. Seki, Y. Shibama, Y. Shibata, T. Shikama, K. Shimada, M. Shimono, J. Shinde, T. Shinya, K. Shinohara, J. Shiraishi, S. Soare, A. Soleto, Y. Someya, S. Sonoda, C. Sozzi, E. Streciwilk-Kowalska, H. Strobel, M. Sueoka, A. Sukegawa, S. Sumida, H. Suzuki, Ma Suzuki, Mi Suzuki, S. Suzuki, T. Suzuki, Y. Suzuki, J. Svoboda, T. Szabolics, T. Szepesi, Y. Takase, M. Takechi, K. Takeda, Y. Takeiri, H. Takenaga, C. Taliercio, N. Tamura, Hiro Tanaka, Hito Tanaka, K. Tanaka, Y. Tanaka, K. Tani, H. Tanigawa, M. Tardocchi, A. Terakado, M. Terakado, T. Terakado, B. Teuchner, B. Tilia, H. Tobari, H. Tobita, K. Tobita, K. Toi, N. Toida, H. Tojo, M. Tokitani, T. Tokuzawa, V. Tormarchio, M. Tomine, A. Torre, T. Totsuka, K. Tsuchiya, N. Tsujii, D. Tsuru, H. Tsutsui, M. Uchida, Y. Ueda, J. Uno, H. Urano, K. Usui, H. Utoh, M. Valisa, M. Vallar, R. Vallcorba-Carbonel, J.-C. Vallet, J. Varela, J. Vega, M. Verrecchia, L. Vieillard, F. Villone, P. Vincenzi, K. Wada, R. Wada, T. Wakatsuki, M. Wanner, F. Watanabe, K. Watanabe, S. Watanabe, T. Wauters, S. Wiesen, M. Wischmeier, M. Yagi, J. Yagyu, M. Yajima, S. Yamamoto, H. Yamanaka, K. Yamauchi, Y. Yamauchi, H. Yamazaki, K. Yamazaki, R. Yamazaki, S. Yamoto, S. Yanagi, K. Yanagihara, S. Yokooka, M. Yokoyama, T. Yokoyama, M. Yoshida, M. Yoshimura, N. Yoshizawa, K. Yuinawa, L. Zani, and P. Zito
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JT-60SA ,superconducting tokamak ,risk mitigation measures ,integrated commissioning ,maintenance and enhancement ,international collaboration ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Superconducting (SC) tokamak JT-60SA plays an essential role in fusion research and development by supporting and complementing the ITER project, providing directions to the DEMO design activity and fostering next generation scientists and engineers. Since the short circuit incident at the terminal joints of equilibrium field coil #1 during the integrated commissioning (IC) in March 2021, both EU and JA implementing agencies (IAs) have examined how to ensure safe operation of JT-60SA by mitigating the risk of possible discharge occurrence inside the cryostat. Based on the experience of the global Paschen tests, the IAs have established a strategy of risk mitigation measures, which is a combination of (i) reinforcement of insulation, (ii) avoiding unnecessary voltage application to the coil systems and (iii) immediate de-energization of the coils when deteriorated vacuum conditions are detected. Thanks to the considerable efforts of the Integrated Project Team members, the IC restarted in May 2023. After confirmation of the SC state of the coil systems (TF, EF and CS), the coil energization test and the plasma operation phase 1 (OP-1) started. The first plasma was successfully achieved on 23 October 2023 with a limited value of voltage and current applied to the coils. The plasma configuration control was also confirmed with low plasma current and low auxiliary heating power conditions. Based on the IO–F4E–QST collaboration, activities of JT-60SA have been shared with the IO and provided an important lesson for ITER assembly and commissioning, and will provide an outstanding contribution to fusion research at large. After OP-1, maintenance & enhancement phase 1 (M/E-1) starts from January 2024, in which in-vessel components are installed, and heating and diagnostic systems are extensively upgraded to allow a high power heating experiment planned in OP-2. In order to make the best use of JT-60SA, a newly organized JT-60SA experiment team will refine the research plan for the future high heating power operation phase.
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- 2024
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11. Factors predicting the outcome of allergen-specific nasal provocation test in children with grass pollen allergic rhinitis
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M. Barreto, S. Tripodi, S. Arasi, M. Landi, M. Montesano, S. Pelosi, E. Potapova, I. Sfika, V. Villella, A. Travaglini, M. A. Brighetti, P. M. Matricardi, and S. Dramburg
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seasonal allergic rhinitis ,nasal provocation test (NPT) ,pollen allergy ,component-resolved diagnostics ,precision medicine ,e-Diary ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundNasal provocation testing (NPT) is a reference methodology to identify the culprit allergen in patients with allergic rhinitis. Selecting the right allergen for NPT is particularly difficult in poly-sensitized patients with seasonal allergic rhinitis (SAR). Predictors of NPT outcomes may facilitate the proper use of this test or even substitute it.ObjectiveTo identify predictors of grass pollen NPT outcome from an array of clinical data, e-diary outcomes, and allergy test results in poly-sensitized pediatric patients with SAR.MethodsPoly-sensitized, SAR patients with grass pollen allergy, participating in the @IT.2020 pilot project in Rome and Pordenone (Italy), participated in a baseline (T0) visit with questionnaires, skin prick testing (SPT), and blood sampling to measure total (ImmunoCAP, TFS, Sweden) and specific IgE antibodies to grass pollen extracts and their major allergenic molecules (ESEP, Euroimmun Labordiagnostika, Germany). During the pollen season, patients filled the AllergyMonitor® e-diary app measuring their symptoms, medication intake, and allergy-related well-being via the Visual Analogue Scale (VAS). After the pollen season (T1), patients answered clinical questionnaires and underwent a nasal provocation test (NPT) with grass pollen extract.ResultsWe recruited 72 patients (age 14.3 ± 2.8 years, 46 males) sensitized to grass and/or other pollens, including olive (63; 87.5%) and pellitory (49; 68.1%). Patients positive to grass pollen NPT (61; 84.7%), compared to the negative ones, had worse VAS values in the e-diary, larger SPT wheal reactions, and higher IgE levels, as well as specific activity to timothy and Bermuda grass extracts, rPhl p 5 and nCyn d 1. A positive NPT to grass pollen was predicted by an index combining the specific activity of IgE towards Phl p 5 and Cyn d 1 (AUC: 0.82; p
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- 2023
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12. Regional evaluation of the performance of the global CAMS chemical modeling system over the United States (IFS cycle 47r1)
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J. E. . Williams, V. Huijnen, I. Bouarar, M. Meziane, T. Schreurs, S. Pelletier, V. Marécal, B. Josse, and J. Flemming
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Geology ,QE1-996.5 - Abstract
The Copernicus Atmosphere Monitoring Service (CAMS) provides routine analyses and forecasts of trace gases and aerosols on a global scale. The core is the European Centre for Medium Range Weather Forecasts (ECMWF) Integrated Forecast System (IFS), where modules for atmospheric chemistry and aerosols have been introduced and which allows for data assimilation of satellite retrievals of composition. We have updated both the homogeneous and heterogeneous NOx chemistry applied in the three independent tropospheric–stratospheric chemistry modules maintained within CAMS, referred to as IFS(CB05BASCOE), IFS(MOCAGE) and IFS(MOZART). Here we focus on the evaluation of main trace gas products from these modules that are of interest as markers of air quality, namely lower-tropospheric O3, NO2 and CO, with a regional focus over the contiguous United States. Evaluation against lower-tropospheric composition reveals overall good performance, with chemically induced biases within 10 ppb across species for regions within the US with respect to a range of observations. The versions show overall equal or better performance than the CAMS reanalysis, which includes data assimilation. Evaluation of surface air quality aspects shows that annual cycles are captured well, albeit with variable seasonal biases. During wintertime conditions there is a large model spread between chemistry schemes in lower-tropospheric O3 (∼ 10 %–35 %) and, in turn, oxidative capacity related to NOx lifetime differences. Analysis of differences in the HNO3 and PAN formation, which act as reservoirs for reactive nitrogen, revealed a general underestimate in PAN formation over polluted regions, likely due to too low organic precursors. Particularly during wintertime, the fraction of NO2 sequestered into PAN has a variability of 100 % across chemistry modules, indicating the need for further constraints. Notably, a considerable uncertainty in HNO3 formation associated with wintertime N2O5 conversion on wet particle surfaces remains. In summary, this study has indicated that the chemically induced differences in the quality of CAMS forecast products over the United States depends on season, trace gas, altitude and region. While analysis of the three chemistry modules in CAMS provide a strong handle on uncertainties associated with chemistry modeling, the further improvement of operational products additionally requires coordinated development involving emissions handling, chemistry and aerosol modeling, complemented with data-assimilation efforts.
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- 2022
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13. New insights regarding origin of monosomy occurrence in early developing embryos as demonstrated in preimplantation genetic testing
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N. Samara, S. Peleg, T. Frumkin, V. Gold, H. Amir, Einat Haikin Herzberger, A. Reches, Y. Kalma, Dalit Ben Yosef, F. Azem, and M. Malcov
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Early embryo aneuploidy ,Haplotype ,Monosomy ,Paternal origin ,Polymorphic markers ,Preimplantation genetic testing ,Genetics ,QH426-470 - Abstract
Abstract Introduction Analyses of miscarriage products indicate that the majority of aneuploidies in early developing embryos derive from errors occurring during maternal meiosis and the paternal contribution is less than 10%. Our aim was to assess the aneuploidy (mainly monosmies) frequencies at the earliest stages of embryo development, 3 days following fertilization during In vitro fertilization (IVF) treatments and to elucidate their parental origin. Later, we compared monosomies rates of day 3 to those of day 5 as demonstrated from Preimplantation Genetic Testing for Structural chromosomal Rearrangement (PGT-SR) results. Methods For a retrospective study, we collected data of 210 Preimplantation Genetic Testing for Monogenic Disorder (PGT-M) cycles performed between years 2008 and 2019.This study includes 2083 embryos, of 113 couples. It also included 432 embryos from 90 PGT-SR cycles of other 45 patients, carriers of balanced translocations. Defining the parental origin of aneuploidy in cleavage stage embryos was based on haplotypes analysis of at least six informative markers flanking the analyzed gene. For comprehensive chromosomal screening (CCS), chromosomal microarray (CMA) and next generation sequencing (NGS) was used. Results We inspected haplotype data of 40 genomic regions, flanking analyzed genes located on 9 different chromosomes.151 (7.2%) embryos presented numerical alterations in the tested chromosomes. We found similar paternal and maternal contribution to monosomy at cleavage stage. We demonstrated paternal origin in 51.5% of the monosomy, and maternal origin in 48.5% of the monosomies cases. Conclusion In our study, we found equal parental contribution to monosomies in cleavage-stage embryos. Comparison to CCS analyses of PGT-SR patients revealed a lower rate of monosomy per chromosome in embryos at day 5 of development. This is in contrast to the maternal dominancy described in studies of early miscarriage. Mitotic errors and paternal involvement in chemical pregnancies and IVF failure should be re-evaluated. Our results show monosomies are relatively common and may play a role in early development of ART embryos.
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- 2022
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14. The insemination status and social context influences quail laying and social behavior: A novel experimental set up
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S. Pellegrini, G.A. Orso, R.H. Marin, and D.A. Guzman
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Japanese quail ,egg laying behavior ,behavioral need ,Animal culture ,SF1-1100 - Abstract
ABSTRACT: Japanese quails in wild life live in small groups with females being even solitary during the laying period. Although it is a poultry species widely used for egg production, information regarding laying behavior motivations or influencing variables is scarce. Our study focuses on evaluating along 7 d the quail laying behavior in a novel environmental set up. This set up allows the female to choose between remaining separated from a conspecific in one side of the apparatus or to voluntarily enter their space (box-mate side) and interact with it. We evaluated whether the female insemination status prior to enter the environmental set up, and the presence of a female or a male partner in the box-mate side can influence their laying and social behavior. Thus, 4 experimental groups were established. Females spent a higher (P < 0.05) percentage of time in the box-mate side than in their separated sector in all groups. In 3 of the 4 experimental groups (non-inseminated females interacting with a female or a male box-mate, and inseminated females interacting with a male box-mate) females also laid a greater percentage (≥65%, P < 0.05, in all cases) of eggs in the box-mate sector than in their separated sector. However, the group of inseminated females that interacted with a female box-mate shifted their egg distribution and laid equally between both sides of the apparatus. Aggressive social interactions were reduced (P < 0.05) throughout the testing days but this was depending upon the female insemination status and the sex of their box-mate. Findings suggest that females can change their laying side choice when they are inseminated but depending on the sex identity of their box-mate partners. Thus, providing quail female breeders with the option of laying their eggs in separated enclosures from conspecifics could be key to favor their well-being.
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- 2023
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15. Early onset developmental and epileptic encephalopathy and Rett-like phenotype in a 15-year-old girl affected by Cornelia de Lange syndrome type 2 due to a SMC1A gene mutation
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L. Parmeggiani, F. Stanzial, E. Menna, E. Boni, F. Manzoni, F. Benedicenti, and S. Pellegrin
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SMC1A ,Developmental and epileptic encephalopathy ,Epilepsy ,Neurodevelopmental disorder ,Developmental regression ,PCDH19-related epilepsy ,Neurology. Diseases of the nervous system ,RC346-429 ,Neurophysiology and neuropsychology ,QP351-495 - Abstract
Developmental and epileptic encephalopathies (DEE) are conditions in which a mutated gene may cause abnormal functioning of the central nervous system, resulting in both encephalopathy and epileptogenesis. We present a case of a girl with a DEE characterized by a Rett-like phenotype in association with febrile and afebrile clusters of focal seizures. The girl presented typical development until the age of 18 months, followed by regression. The first febrile bilateral tonic-clonic seizure was observed at 30 months of age, and the following month seizures recurred in clusters of several episodes per day every 10 days. These seizures were characterized by behavioural arrest, emotional symptoms, head turning, and followed by bilateral tonic-clonic seizures. The administration of valproic acid and levetiracetam led to prolonged seizure control. However, from the age of 7 years, she had monthly recurrent clusters of focal seizures and non-convulsive status epilepticus which occurred at different ages. Brain and spinal cord MRI showed mild non-progressive hemispheric cerebellar atrophy. A next generation sequencing panel for epilepsy identified the de novo splicing mutation c.2973+1G>A of the SMC1A gene.
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- 2023
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16. Participation of active consumers in the electricity system: Design choices for consumer governance
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S. Pelka, E.J.L. Chappin, M. Klobasa, and L.J. de Vries
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Energy market design ,Demand response ,Distributed energy resources ,Variable tariff ,Local energy market ,Virtual power plant ,Energy industries. Energy policy. Fuel trade ,HD9502-9502.5 - Abstract
Household electricity use has an increasing impact on the overall energy system. Numerous proposals have been made to support households to consume electricity in a system-friendlier manner. By breaking these proposals down into functions and how they are performed, this paper identifies four distinctive governance designs: energy communities, variable electricity tariffs, local energy markets and virtual power plants. None covers all the functions required and each addresses different trade-offs that households face. Energy communities focus on investing in energy assets, while the others target the operation of households’ assets, including demand response. Virtual power plants attract profit-oriented consumers, while the others primarily target normative consumers.
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- 2022
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17. The Care Coordinator’s Tasks During the Implementation of an Integrated Care Pathway for Older Patients: A Qualitative Study Based on the French National 'Health Pathway of Seniors for Preserved Autonomy' Pilot Program
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L. Douze, C. Di Martino, M. Calafiore, L. Averlant, Ch Peynot, M. Lotin, A. Delesalle, D. Dambre, M. Egot, A. Fabianek, M. M Defebvre, C. Bugny, J. Thébault, F. Puisieux, S. Pelayo, and J. B. Beuscart
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older adults ,frailty ,care coordinator ,integrated care ,task analysis ,Medicine (General) ,R5-920 - Abstract
Background: Although integrated care and care coordination are known to be beneficial for older adults’ population, the specific tasks of a Care Coordinator (CC) for integrated care pathways for this population have not been studied in detail. Setting & Subjects: The French national pilot program PAERPA provided an integrated care pathway for older adults. In North France, a CC was recruited to support patients and professionals. Objectives: (i) To analyse the CC’s tasks in an integrated care pathway for older patients, and (ii) to record perceptions on the CC’s tasks among the participating general practitioners (GP) and community pharmacists. Design & Methods: Qualitative, two-phase study: (i) Task analysis of the CC’s tasks, to compare the planned and actual tasks; (ii) semi-structured interviews among GPs and community pharmacists involved in the pathway. Results: (i) The task analysis showed that the CC’s actual tasks differed from planned tasks. The CC was only meant to be involved in the early stages of the process; actually, the CC undertook more or even unforeseen tasks in coordination, communication, and administrative support throughout the care pathways. (ii) The 28 interviewed healthcare professionals considered the CC’s tasks to be essential to the success of pathways. They appreciated the CC’s administrative support. However, CC’s tasks related to interprofessional communication, and patient and family information, were controversially perceived among GPs and pharmacists. Conclusions: The CC’s tasks in an integrated care pathway for older adults showed that the CC’s overall workload was greater than expected and appreciated by healthcare professionals.
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- 2022
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18. Influenza D Virus in Cattle and Swine in Piedmont Region, North-Western Italy
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O.A. Sparasci, F. Rizzo, M. Marchino, F. Cerutti, C. Guglielmetti, F. Grosjacques, E. Muratore, B. Sona, P. Biolatti, S. Peletto, L. Masoero, P. Acutis, and M.L. Mandola
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Infectious and parasitic diseases ,RC109-216 - Abstract
Purpose: This study aimed to investigate the circulation of Influenza D Virus – IDV (a new genus of the Orthomyxoviridae family) in cattle and swine in Piedmont (Cuneo province) by active and passive surveillance and by a retrospective study on swine archived samples collected in the same area in 2014-2015. Methods & Materials: According to risk-based criteria, 103 cattle and 44 pig farms (both fattening and reproduction) were selected for the sampling of nasal swabs, lungs and oral fluids. In each farm, 15 to 30 nasal swabs were collected from both healthy and symptomatic subjects. RNA extraction was performed with an automatic Maxwell® RCS 48 Promega extractor according to the manufacturer specifications. Oral fluid collection from swine was carried out using cotton ropes and RNA was then isolated by phenol-chloroform extraction from supernatant. As for lungs, a portion of approximately 25 mg of tissue was extracted in phenol-chloroform. Finally, the retrospective study was carried out on RNA extracts from pig nasal swabs and lungs collected in 2014-2015, as part of another research project. RNAs were amplified by One Step RT-PCR for Influenza D using the protocol designed on the region of the gene encoding the Pb1 protein. Results: Between 2018 and 2020 more than 600 samples were collected from 48 cattle farms and 35 pig farms. A total of 482 bovine nasal swabs, 44 bovine lungs, 105 swine oral fluids and 75 pig nasal swabs were processed for the identification of IDV RNA. In the retrospective study, 857 swine nasal swabs and 22 lungs from 43 farms were tested for IDV. Preliminary results showed 7 cattle farms (4 fattening, 3 reproduction/dairy ones) and 1 pig breeding farm positive for IDV, from the active surveillance and the retrospective study, respectively. Furthermore, viral isolation from positive samples on MDCK cells is ongoing. Conclusion: Our study confirms the presence of IDV in Piedmont region, in Cuneo province. Positivity found mainly in cattle and mostly during winter supports the hypothesis that cattle are the main reservoir of the virus and that winter is the season with the highest risk of infection.
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- 2022
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19. Phoxonic glass cavities based on whispering gallery mode resonators
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D. Farnesi, S. Berneschi, G. Frigenti, G. Nunzi Conti, S. Pelli, P. Feron, T. Murzina, M. Ferrari, and S. Soria
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Whispering gallery modes ,Optical resonators ,Microspheres ,Microbubbles ,Lasers ,Non-linear optics ,Applied optics. Photonics ,TA1501-1820 ,Optics. Light ,QC350-467 - Abstract
A variety of studies have been performed on WGM microresonators made of different materials and exploiting very high quality factors. This feature has allowed their use in a broad variety of applications including micro-lasers, optical filtering and switching, frequency conversion through non-linear effects, RF photonics and sensing. The easiest way to shape a glass spheroid with high quality factor is to use the surface tension during the thermal reflow of a highly transparent amorphous dielectric. Depending on the application, alternatives shapes like micro-bubbles or micro-bottles can be implemented in order to obtain specific performances. This manuscript reports the results we obtained on micro-laser sources in erbium doped microspheres, parametric frequency conversion in silica microspheres, stimulated Brillouin scattering in silica microbubbles, and non-linear effects in polymer coated or fluorophore filled glass microcavities.
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- 2021
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20. PB2326: SAFE AND EFFECTIVE PROPHYLAXIS WITH PLASMA-DERIVED FACTOR X CONCENTRATE IN AN ELDERLY PATIENT WITH HEREDITARY FACTOR X DEFICIENCY
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H. Patel, S. Peltier, K. Clark, and M. T. Reding
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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21. Longitudinal safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine in children aged 4-11 years with juvenile-onset autoimmune inflammatory rheumatic diseases: A prospective multicenter study.
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Eviatar T, Ziv A, Oved A, Miller-Barmak A, Pappo A, Livny R, Amarilyo G, Aviel YB, Naor R, Pel S, Furer V, Elkayam O, Uziel Y, and Heshin-Bekenstein M
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- Humans, Child, Male, Female, Child, Preschool, Prospective Studies, Longitudinal Studies, Israel epidemiology, Autoimmune Diseases immunology, SARS-CoV-2 immunology, COVID-19 Vaccines adverse effects, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, Vaccine Efficacy, Antibodies, Viral blood, Antibodies, Viral immunology, Immunogenicity, Vaccine, BNT162 Vaccine immunology, BNT162 Vaccine administration & dosage, COVID-19 prevention & control, COVID-19 immunology, Rheumatic Diseases immunology
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This prospective, longitudinal, multicenter study assessed the safety and efficacy of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine among children 4-11 years-old with autoimmune inflammatory rheumatologic disease (AIIRD), compared to healthy controls. The study was conducted from 11/2021-12/2022 at 4 tertiary pediatric rheumatology units in Israel. Participants received at least 2 vaccine doses. Safety analysis included adverse events and disease activity measures. Efficacy was assessed by COVID-19 infection rates. Immunogenicity was evaluated in a subset of participants using anti- receptor binding domain antibody titers. Thirty-one children with AIIRD and 45 immunocompetent controls with similar baseline characteristics were included. Safety profile was favorable, with mild or no adverse events reported. The adverse event rates were similar in the AIIRD and control groups after the first (27 (60 %) vs. 14 (45.2 %), p = 0.2977) and the second vaccine doses (22 (49.0 %) vs. 18 (58.1 %), p = 0.5799), respectively. AIIRD activity remained stable and low after vaccination. Breakthrough COVID-19 infection rates were similar between groups, with 15 (48.4 %) in the AIIRD vs. 25 (55.6 %) in the control group (p = 0.7029). All reported COVID-19 infections in the AIIRD group and 18 (72 %) in the control group were symptomatic (p = 0.033), although symptoms were generally mild, with no severe disease. The safety of the BNT162b2 COVID-19 vaccine was excellent in children ages 4-11 years with AIIRD and healthy controls. Efficacy between groups was similar., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2024
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22. Tocilizumab Dose Tapering Based on a Model-Based Algorithm is Feasible in Clinical Practice: A Short Communication.
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Hooijberg F, Layegh Z, Leeuw M, Boekel L, van den Berg SPH, Ruwaard J, Bastida C, Huitema ADR, Pel S, Elkayam O, de Vries A, Nurmohamed M, Rispens T, Dorlo TPC, and Wolbink G
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- Humans, Double-Blind Method, Female, Middle Aged, Male, Antirheumatic Agents administration & dosage, Antirheumatic Agents pharmacokinetics, Antirheumatic Agents therapeutic use, Antirheumatic Agents blood, Drug Tapering methods, Feasibility Studies, Dose-Response Relationship, Drug, Aged, Adult, Antibodies, Monoclonal, Humanized pharmacokinetics, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized therapeutic use, Arthritis, Rheumatoid drug therapy, Algorithms, Drug Monitoring methods
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Background: Tocilizumab in the treatment of rheumatoid arthritis (RA) is a potential candidate for concentration-guided tapering because the standard dose of tocilizumab results in a wide range of serum concentrations, usually above the presumed therapeutic window, and an exposure-response relationship has been described. However, no clinical trials have been published to date on this subject. Therefore, the objective of this study was to assess the feasibility of the tapering of intravenous (iv) tocilizumab with the use of a pharmacokinetic model-based algorithm in RA patients., Methods: A randomized controlled trial with a double-blind design and follow-up of 24 weeks was conducted. RA patients who received the standard of tocilizumab for at least the past 24 weeks, which is 8 mg/kg every 4 weeks, were included. Patients with a tocilizumab serum concentration above 5 mg/L at trough were randomized between concentration-guided dose tapering, referred to as therapeutic drug monitoring (TDM), or the standard 8 mg/kg dose. In the TDM group, the tocilizumab dose was tapered with a recently published model-based algorithm to achieve a target concentration of 4-6 mg/L after 20 weeks of dose tapering., Results: Twelve RA patients were included and 10 were randomized between the TDM and standard dose group. The study was feasible regarding the predefined feasibility criteria and patients had a positive attitude toward therapeutic drug monitoring. In the TDM group, the tocilizumab trough concentration within patients decreased on average by 24.5 ± 18.3 mg/L compared with a decrease of 2.8 ± 12 mg/L in the standard dose group. None of the patients in the TDM group reached the drug range of 4-6 mg/L. Instead, tocilizumab concentrations of 1.6 and 1.5 mg/L were found for the 2 patients who completed follow-up on the tapered dose. No differences in RA disease activity were observed between the 2 study groups., Conclusions: This study was the first to show that it is feasible to apply a dose-reduction algorithm based on a pharmacokinetic model in clinical practice. However, the current algorithm needs to be optimized before it can be applied on a larger scale., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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23. Ex-vivo Cell-based Assay for Assessment of Response to TNF Inhibitors in Patients with Rheumatic Diseases.
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Gertel S, Rokach M, Polachek A, Levartovsky D, Broyde A, Furer V, Dovrat TO, Wollman J, Pel S, Neufeld Y, and Elkayam O
- Abstract
Objective: TNF inhibitors (TNFi) comprise 5 products whose structure and signalling differ. An individual patient with a rheumatic disease may respond to one TNFi but not to another. In addition, 30-40% of the patients respond inadequately to TNFi. The different TNFi downstream signalling may lead to their clinical efficacy. Several reports showed that TNFi exhibited differential effects on Th17 cells. We analyzed the different TNFi effects on IL-17A expression in the peripheral blood mononuclear cells (PBMCs) of patients with rheumatic diseases in order to evaluate the predictive capability of responses in an ex-vivo setting., Methods: PBMCs were co-cultured with the different TNFi or medium (control), and IL-17A mRNA levels were analyzed by qPCR. IL-17A expression levels in response to 4 TNFi (except certolizumab pegol) were compared with control. IL-17A expression in the assay was correlated to the clinical responses. Assay sensitivity and specificity for distinguishing responders from non-responders was calculated by receiver-operating characteristic (ROC) analysis., Results: The results of a retrospective cohort of patients with rheumatic diseases (n = 82) correlated with their therapeutic responses to the different TNFi with 89.5% accuracy. The assay predicted the responses of a prospective cohort (n = 54) to specific TNFi with 79% accuracy., Conclusion: This functional assay could assist in predicting the odds for response to TNFi therapy, indicating whether a given patient is likely to respond to a specific TNFi., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2024
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24. Effect of Secukinumab and Tumor Necrosis Factor Inhibitors on Humoral Response to BNT162b2 mRNA Vaccine in Patients With Spondyloarthritis Compared to Immunocompetent Controls.
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Eviatar T, Furer V, Polachek A, Zisman D, Peleg H, Elalouf O, Levartovsky D, Kaufman I, Broyde A, Haddad A, Feld J, Aassi M, Quebe-Fehling E, Alarcon I, Pel S, Paran D, and Elkayam O
- Subjects
- Humans, Tumor Necrosis Factor Inhibitors therapeutic use, mRNA Vaccines, BNT162 Vaccine, Tumor Necrosis Factor-alpha, Treatment Outcome, Methotrexate therapeutic use, Antirheumatic Agents therapeutic use, Spondylarthritis drug therapy, Arthritis, Rheumatoid drug therapy, COVID-19, Breakthrough Infections, Antibodies, Monoclonal, Humanized
- Abstract
Objective: To assess the humoral response to the BNT162b2 mRNA vaccine among patients with spondyloarthritis (SpA) receiving secukinumab (SEC) compared to those receiving tumor necrosis factor inhibitors (TNFi) and immunocompetent controls., Methods: Consecutive patients with psoriatic arthritis or axial SpA receiving SEC (n = 37) or TNFi (monotherapy, n = 109; + methotrexate [MTX], n = 16), immunocompetent controls (n = 122), and patients with rheumatoid arthritis (RA) receiving TNFi therapy (controls, n = 50) were vaccinated with 2 or 3 doses of the BNT162b2 vaccine. We evaluated humoral response, adverse events, and disease activity, and monitored for breakthrough coronavirus disease 2019 (COVID-19) postvaccination., Results: The 2-dose vaccine regimen induced a comparable seropositive response in all study groups. S1/S2 antibody titers (in binding antibody units/mL; mean [SD]) were higher in the SEC group vs the TNFi + MTX-SpA and TNFi-RA groups (192.5 [68.4] vs 104.6 [46.9], P < 0.001, and 143.1 [81.9], P = 0.004). After 6 months, 96.3%, 96.6%, and 80.9% of the SEC, immunocompetent, and TNFi monotherapy-SpA groups ( P = 0.10), respectively; 66.7% of the TNFi + MTX-SpA group ( P = 0.03); and 63% of the TNFi-RA group ( P = 0.004) remained seropositive. S1/S2 antibody titer decline was steeper in the TNFi groups than the SEC group. After the third dose, 100% of the SpA and immunocompetent and 88.9% of the TNFi-RA ( P = 0.25) groups were seropositive. Rate of breakthrough COVID-19 infection was higher in the TNFi groups than in the SEC group (36-37.5% vs 10.8%). No significant between-group differences were observed for postvaccination disease activity and adverse events., Conclusion: SEC did not interfere with the immunogenic response to BNT162b2 vaccine in patients with SpA; however, TNFi therapy was associated with lower S1/S2-antibody titers, faster decline, and higher rate of breakthrough infections., (Copyright © 2024 by the Journal of Rheumatology.)
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- 2024
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25. Safety and Immunogenicity Following the Second and Third Doses of the BNT162b2 mRNA COVID-19 Vaccine in Adolescents with Juvenile-Onset Autoimmune Inflammatory Rheumatic Diseases: A Prospective Multicentre Study.
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Heshin-Bekenstein M, Ziv A, Toplak N, Lazauskas S, Kadishevich D, Ben-Nun Yaari E, Miller-Barmak A, Butbul Aviel Y, Saiag E, Pel S, Elkayam O, Uziel Y, and Furer V
- Abstract
Background: To explore the long-term safety and dynamics of the immune response induced by the second and third doses of the BNT162b2 mRNA COVID-19 vaccine in adolescents with juvenile-onset autoimmune inflammatory rheumatic diseases (AIIRDs) compared with healthy controls., Methods: This international prospective study included adolescents with AIIRDs and controls vaccinated with two (AIIRDs n = 124; controls n = 80) or three (AIIRDs n = 64; controls n = 30) doses of the BNT162b2 vaccine, evaluated for vaccine side-effects, disease activity, COVID-19 breakthrough infection rates and severity, and anti-spike S1/S2 IgG antibody titers in a sample from both groups., Results: The vaccination safety profile was favorable, with most patients reporting mild or no side-effects. The rheumatic disease remained stable at 98% and 100% after the second and third doses, respectively. The two-dose vaccine induced comparable seropositivity rates among patients (91%) and controls (100%), ( p = 0.55), which declined within 6 months to 87% and 100%, respectively ( p = 0.3) and increased to 100% in both groups after the third vaccine dose. The overall post-vaccination COVID-19 infection rate was comparable between patients and controls, 47.6% (n = 59) and 35% (n = 28), respectively; p = 0.5278, with most infections occurring during the Omicron surge. In relation to the last vaccination, time-to-COVID-19 infection was similar between patients and controls, at a median of 5.5 vs. 5.2 months, respectively (log-rank p = 0.1555)., Conclusion: The safety profile of three doses of the BNT162b2 mRNA vaccine was excellent, with adequate humoral response and similar efficacy among patients and controls. These results support the recommendation for vaccinating adolescents with juvenile-onset AIIRDs against COVID-19.
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- 2023
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26. Safety and immunogenicity of BNT162b2 mRNA COVID-19 vaccine in adolescents with rheumatic diseases treated with immunomodulatory medications.
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Heshin-Bekenstein M, Ziv A, Toplak N, Hagin D, Kadishevich D, Butbul YA, Saiag E, Kaufman A, Shefer G, Sharon O, Pel S, Elkayam O, and Uziel Y
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- Young Adult, Humans, Adolescent, COVID-19 Vaccines, BNT162 Vaccine, RNA, Messenger, Prospective Studies, SARS-CoV-2, Symptom Flare Up, Vaccination, COVID-19, Lupus Erythematosus, Systemic complications, Rheumatic Diseases drug therapy, Vaccines adverse effects
- Abstract
Objectives: Adolescents with juvenile-onset autoimmune inflammatory rheumatic diseases (AIIRDs) could be at risk for disease flare secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or to withholding anti-inflammatory therapy. While vaccination can protect against coronavirus disease 2019 (COVID-19), safety and immunogenicity data regarding anti-SARS-CoV-2 vaccines among adolescents with AIIRDs are limited. This international, prospective, multicentre study evaluated the safety and immunogenicity of the BNT162b2 anti-SARS-CoV-2 vaccine among adolescents and young adults with juvenile-onset AIIRDs, 80% of whom are on chronic immunomodulatory therapy., Methods: Vaccine side effects, disease activity and short-term efficacy were evaluated after 3 months in 91 patients. Anti-spike S1/S2 IgG antibody levels were evaluated in 37 patients and 22 controls 2-9 weeks after the second dose., Results: A total of 91 patients and 40 healthy controls were included. The safety profile was good, with 96.7% (n = 88) of patients reporting mild or no side effects and no change in disease activity. However, three patients had transient acute symptoms: two following the first vaccination (renal failure and pulmonary haemorrhage) and one following the second dose (mild lupus flare vs viral infection). The seropositivity rate was 97.3% in the AIIRD group compared with 100% among controls. However, anti-S1/S2 antibody titres were significantly lower in the AIIRD group compared with controls [242 (s.d. 136.4) vs 387.8 (57.3) BAU/ml, respectively; P < 0.0001]. No cases of COVID-19 were documented during the 3 month follow-up., Conclusion: Vaccination of juvenile-onset AIIRD patients demonstrated good short-term safety and efficacy and a high seropositivity rate but lower anti-S1/S2 antibody titres compared with healthy controls. These results should encourage vaccination of adolescents with juvenile-onset AIIRDs, even while on immunomodulation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2022
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27. Immunogenicity induced by two and three doses of the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases and immunocompetent controls: a longitudinal multicentre study.
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Furer V, Eviatar T, Freund T, Peleg H, Paran D, Levartovsky D, Kaufman I, Broyde A, Elalouf O, Polachek A, Feld J, Haddad A, Gazitt T, Elias M, Higazi N, Kharouf F, Gertel S, Pel S, Nevo S, Hagin D, Zisman D, and Elkayam O
- Subjects
- Abatacept therapeutic use, Adult, Antibodies, Viral, Antirheumatic Agents therapeutic use, Humans, Immunoglobulin G therapeutic use, Janus Kinases, Methotrexate therapeutic use, Prospective Studies, Rituximab therapeutic use, Autoimmune Diseases complications, Autoimmune Diseases drug therapy, BNT162 Vaccine immunology, COVID-19 prevention & control, Immunogenicity, Vaccine, Rheumatic Diseases drug therapy
- Abstract
Objectives: To evaluate long-term kinetics of the BNT162b2 mRNA vaccine-induced immune response in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and immunocompetent controls., Methods: A prospective multicentre study investigated serum anti-SARS-CoV-2 S1/S2 IgG titre at 2-6 weeks (AIIRD n=720, controls n=122) and 6 months (AIIRD n=628, controls n=116) after the second vaccine, and 2-6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). T-cell immune response to the third vaccine was evaluated in a small sample., Results: The two-dose vaccine regimen induced a higher humoral response in controls compared with patients, postvaccination seropositivity rates of 100% versus 84.72%, p<0.0001, and 96.55% versus 74.26%, p<0.0001 at 2-6 weeks and at 6 months, respectively. The third vaccine dose restored the seropositive response in all controls and 80.47% of patients with AIIRD, p=0.0028. All patients treated with methotrexate monotherapy, anticytokine biologics, abatacept and janus kinase (JAK) inhibitors regained the humoral response after the third vaccine, compared with only a third of patients treated with rituximab, entailing a 16.1-fold risk for a negative humoral response, p≤0.0001. Cellular immune response in rituximab-treated patients was preserved before and after the third vaccine and was similar to controls. Breakthrough COVID-19 rate during the Delta surge was similar in patients and controls, 1.83% versus 1.43%, p=1., Conclusions: The two-dose BNTb262 regimen was associated with similar clinical efficacy and similar waning of the humoral response over 6 months among patients with AIIRD and controls. The third vaccine dose restored the humoral response in all of the controls and the majority of patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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28. Seroprevalence of SARS-CoV-2 antibodies in patients with autoimmune inflammatory rheumatic diseases.
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Eviatar T, Furer V, Polachek A, Levartovsky D, Elalouf O, Zisapel M, Halperin T, Turner D, Paran D, Pel S, Nevo S, and Elkayam O
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- Antibodies, Viral, Cross-Sectional Studies, Humans, Immunoglobulin G, SARS-CoV-2, Seroepidemiologic Studies, COVID-19 epidemiology, Rheumatic Diseases diagnosis, Rheumatic Diseases drug therapy, Rheumatic Diseases epidemiology, Rheumatic Fever
- Abstract
Objectives: To assess the prevalence of anti-SARS-CoV-2 antibodies in autoimmune inflammatory rheumatic disease (AIIRD) patients, and to define clinical factors associated with seropositivity., Methods: A cross sectional study was conducted at a tertiary rheumatology department in Israel. Consecutive patients completed a questionnaire and were tested for SARS-CoV-2 anti-nucleoprotein IgG (N-IgG). If this was positive, an anti-S1/S2 spike IgG (S-IgG) test was done. If both were positive, the patient was considered seropositive. Seropositive patients were retested after 3 months., Results: The study included 572 AIIRD patients. Thirty patients were found seropositive, for a seroprevalence of 5.24%. The seropositive rate was significantly lower for patients treated with immunosuppressive medications (3.55%, p≤0.01), and specifically for patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) (2.7%, p≤0.05). These associations remained significant in the multivariate regressions adjusting for age, sex and exposure to a known COVID-19 patient. A second serology test 3 months later was collected in 21 of the 30 seropositive patients. In a mean±standard deviation (SD) of 166.63±40.76 days between PCR and second serology, 85% were still positive for N-IgG, and 100% were still positive for S-IgG, with a higher mean±SD titre compared to the first S-IgG (166.77±108.77 vs. 132.44±91.18, respectively, p≤0.05)., Conclusions: Humoral response to SARS-CoV-2 in AIIRD patients may be affected be immunosuppressive treatment, especially bDMARDs. In patients with AIIRD, titres of SARS-CoV-2 IgG antibodies, especially N-IgG antibodies, fade with time, while S-IgG antibodies persist.
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- 2022
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29. Predictors of Immunogenic Response to the BNT162b2 mRNA COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases Treated with Rituximab.
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Furer V, Eviatar T, Zisman D, Peleg H, Braun-Moscovici Y, Balbir-Gurman A, Paran D, Levartovsky D, Zisapel M, Elalouf O, Kaufman I, Broyde A, Polachek A, Feld J, Haddad A, Gazitt T, Elias M, Higazi N, Kharouf F, Pel S, Nevo S, and Elkayam O
- Abstract
Treatment with rituximab (RTX) blunts SARS-CoV-2 vaccination-induced humoral response. We sought to identify predictors of a positive immunogenic response to the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) treated with RTX (AIIRD-RTX). We analyzed 108 AIIRD-RTX patients and 122 immunocompetent controls vaccinated with BNT162b2 mRNA participating in a multicenter vaccination study. Immunogenicity was defined by positive anti-SARS-CoV-2 S1/S2 IgG. We used a stepwise backward multiple logistic regression to identify predicting factors for a positive immunogenic response to vaccination and develop a predicting calculator, further validated in an independent cohort of AIIRD-RTX BNT162b2 mRNA vaccinated patients ( n = 48). AIIRD-RTX patients who mounted a seropositive immunogenic response significantly differed from patients who did not by a lower number of RTX courses (median (range) 3 (1-10) vs. 5 (1-15), p = 0.007; lower cumulative RTX dose (mean ± SD) 6943.11 ± 5975.74 vs. 9780.95 ± 7240.12 mg, p = 0.033; higher IgG level prior to last RTX course (mean ± SD), 1189.78 ± 576.28 vs. 884.33 ± 302.31 mg/dL, p = 0.002), and extended interval between RTX treatment and vaccination, 469.82 ± 570.39 vs. 162.08 ± 160.12 days, p = 0.0009, respectively. Patients with ANCA-associated vasculitis and inflammatory myositis had a low likelihood of a seropositive immunogenic response compared to patients with rheumatoid arthritis, odds ratio (OR) 0.209, 95% confidence interval (CI) 0.046-0.96, p = 0.044 and OR 0.189, 95% CI 0.036-0.987, p = 0.048, respectively. Based on these findings, we constructed a calculator predicting the probability of a seropositive immunogenic response following BNT162b2 mRNA vaccination which performed with 90.5% sensitivity, 59.3% specificity, and 63.3% positive and 88.9% negative predictive values. In summary, the predicting calculator could guide clinicians for optimal timing of BNT162b2 mRNA vaccination in AIIRD-RTX patients.
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- 2022
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30. T cell functions of psoriatic arthritis patients are regulated differently by TNF, IL-17A and IL-6 receptor blockades in vitro.
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Gertel S, Polachek A, Furer V, Levartovsky D, Sidis H, Pel S, Paran D, and Elkayam O
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- Humans, Leukocytes, Mononuclear, Receptors, Interleukin-6, T-Lymphocytes, Arthritis, Psoriatic drug therapy, Interleukin-17
- Abstract
Objectives: The impact of biologics used in PsA management on T cells is unknown. This study evaluated the effect of tumour necrosis factor-alpha (TNFα), interleukin-17A (IL-17A), and IL-6 receptor (IL-6R) blockers on T cell function in PsA patients and healthy controls peripheral blood mononuclear cells (PBMCs)., Methods: A total of 111 PsA patients and 32 healthy controls were recruited. PBMCs were co-cultured in presence of the biologics. T cell activation and proliferation were analysed by flow cytometry and cytokines in supernatants were measured by ELISA. The effect of biologics on lymphocyte proliferation was determined in response to phytohemagglutinin (PHA)., Results: Activated CD4+CD25+ T cells were significantly reduced by adalimumab (ADA) in PsA patients as compared to medium, ixekizumab (IXE), and tocilizumab (TCZ), while in healthy controls, ADA reduced the activated CD4+CD25+ T cells non-significantly. Elevated TNFα and IL-1β levels were produced in supernatants of PsA patients as compared to healthy controls. TNFα, IL-17A, IL-1β, and MMP-3 levels were reduced by ADA compared to medium (p<0.0001, p<0.0004, p<0.04, p<0.04, respectively). IXE reduced IL-17A (p<0.0001) but not the other cytokines. ADA had higher susceptibility to inhibit PHA-induced proliferation in both PsA patients and healthy controls (p<0.03) as compared to IXE and TCZ., Conclusions: Both TNF and IL-17A blockers are suitable for PsA treatment, but exhibit different activity on T cells. Moreover, the study reveals part of the mechanism exerted by ADA and provides a possible explanation for TCZ inefficacy in PsA.
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- 2022
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