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Human Health Risk Assessment (HHRA) is a widely applied method to make decisions about the environmental status of sites affected by toxic substances. Its conclusions are affected by the variability and uncertainty of the input variables in the HHRA model. The aim of this work is to apply an algorithm based on 2D Monte Carlo simulations to integrate the variability and uncertainty of exposure factors, concentration, and bioaccessibility, reported by various information sources, to assess and compare their influence on the risk outcome. The method is applied to a specific case study of exposure of children to arsenic from accidental soil ingestion in a residential setting in the city of Madrid (Spain) by combining information from 12 studies. The consideration of the variability and uncertainty of the exposure parameters in the Baseline Risk Assessment (BRA, deterministic) resulted in a greater reduction in the numerical value of risk estimations than that produced by considering only the bioaccessibility factor. The results of the Probabilistic Risk Assessment (PRA) showed that the risk distribution was more sensitive to the variabilities of the accidental soil intake rate and the total arsenic concentration than to other variables such as bioaccessibility. In this case study, the uncertainty introduced by using the "default" reasonable maximum exposure factors in the HHRA model and the variability of the concentration term produce overestimates of risk that are at least in the range of those produced by omitting the bioaccessibility term. Thus, the inclusion of bioaccessibility is, alone, insufficient to improve the HHRA since the selection of the exposure factors can significantly affect the estimates of risk for the soil ingestion pathway. In other sites or for other contaminants, however, the role of the uncertainties associated with the bioaccesible fraction could be more pronounced. The method applied in this work may be useful in updating exposure factors to reduce uncertainties in HHRAs.

Objective: To evaluate whether the quantification of bone marrow edema (BMO) of the sacroiliac (SI) joints by magnetic resonance imaging (MRI) improves capacity for axial spondyloarthritis (axSpA) classification in comparison with the assessment of sacroiliitis by Assessment of SpondyloArthritis international Society (ASAS) classification criteria.Method: This prospective study from the ESPeranza cohort involved 66 subjects with an available MRI of the SI joints at baseline. This subgroup includes patients with axSpA (n = 28), peripheral spondyloarthritis (n = 10), and other diagnoses that were not spondyloarthritis (n = 28). Measures of diagnostic usefulness [area under the curve (AUC), sensitivity, specificity, Youden's J statistic, positive and negative likelihood ratios (LR+ and LR-)] were calculated for MRI of the SI joints according to ASAS criteria and for MRI quantified by means of SCAISS (Spanish tool for semi-automatic quantification of sacroiliac inflammation by MRI in spondyloarthritis). This analysis was stratified in patients who were human leucocyte antigen (HLA)-B27 positive and negative.Results: The AUC value with BMO quantification was 0.919 [95% confidence interval (CI) 0.799-1] for HLA-B27-positive patients and 0.884 (95% CI 0.764-1) for HLA-B27-negative patients. A SCAISS cut-off point of 80 units obtained a specificity of 94.4% and LR+ 7.5, while assessment by ASAS criteria showed a specificity value of 90% and LR+ 6.4.Conclusion: For patients with suspected axSpA, quantification of BMO improves the predictive capacity of MRI of the SI joints, for both HLA-B27-positive and HLA-B27-negative patients.Axial spondyloarthritis (axSpA) has a dramatic impact on physical function and quality of life (1). Despite its significant impact, patients with axSpA are normally diagnosed several years after presenting symptoms (2). In this respect, magnetic resonance imaging (MRI) of the sacroiliac (SI) joints has gained significance over the past decade, particularly in the early stages of the disease. Nowadays, imaging tests and human leucocyte antigen (HLA)-B27 testing are among the most important diagnostic procedures for patients with suspected axSpA.

Resumen Antecedentes y objetivo La satisfaccion del paciente se ha convertido en un indicador fundamental de calidad asistencial. El objetivo de este trabajo fue traducir, adaptar y validar una version en espanol del cuestionario de satisfaccion en Dermatologia (PSQ-18) en una muestra de pacientes con patologia dermatologica. Material y metodos El cuestionario traducido y adaptado al castellano se obtuvo tras un proceso de traduccion-retrotraduccion acorde a las recomendaciones internacionales. La consistencia interna se determino mediante el alfa de Cronbach (α) y la validez de constructo a traves de un analisis factorial confirmatorio. El coeficiente de correlacion intraclase se calculo utilizando el test-retest, despues de administrar por segunda vez el cuestionario a una muestra de participantes seleccionados de forma aleatoria con un intervalo de 14-21 dias. Resultados Un total de 240 pacientes cumplimentaron correctamente la version del cuestionario consensuada por los investigadores. El analisis de fiabilidad mostro una alta consistencia interna para la version adaptada (Cronbach alpha global 0,834) y el analisis factorial confirmatorio mostro un buen ajuste del modelo para la estructura propuesta inicialmente por los autores del cuestionario. El coeficiente de correlacion intraclase se considero adecuado para cada uno de los items de la escala (CCI > 0,8). Conclusiones El PSQ-18 adaptado culturalmente al espanol ha demostrado ser un instrumento valido, sensible y fiable para medir la satisfaccion en pacientes dermatologicos.

Resumen Las tecnicas de imagen desempenan un papel fundamental en el diagnostico inicial y seguimiento de la enfermedad inflamatoria intestinal. La ecografia intestinal tiene alta sensibilidad y especificidad en la sospecha de la enfermedad de Crohn, en la deteccion de actividad inflamatoria y permite el diagnostico temprano de complicaciones intraabdominales, como estenosis, fistulas y abscesos; ademas, ha demostrado su utilidad en la monitorizacion del tratamiento y en la recurrencia posquirurgica. El desarrollo tecnico de los equipos de ecografia, la incorporacion de avances tecnologicos como el contraste ecografico o la elastografia y, sobre todo, una mayor experiencia, han impulsado su papel en la evaluacion de la patologia del tubo digestivo. La ecografia es particularmente atractiva gracias a su amplia disponibilidad, su inocuidad, bajo coste y buena reproducibilidad, ya que puede repetirse de forma facil y bien tolerada por el paciente durante el seguimiento. Esta revision resume el papel de la ecografia intestinal en la deteccion y seguimiento de pacientes con enfermedad inflamatoria intestinal.

Imaging techniques play a fundamental role in the initial diagnosis and follow-up of inflammatory bowel disease. Intestinal ultrasound has high sensitivity and specificity in patients with suspected Crohn's disease and in the detection of inflammatory activity. This technique enables the early diagnosis of intra-abdominal complications such as stenosis, fistulas, and abscesses. It has also proven useful in monitoring the response to treatment and in detecting postsurgical recurrence. Technical improvements in ultrasound scanners, technological advances such as ultrasound contrast agents and elastography, and above all increased experience have increased the role of ultrasound in the evaluation of the gastrointestinal tract. The features that make ultrasound especially attractive include its wide availability, its noninvasiveness and lack of ionizing radiation, its low cost, and its good reproducibility, which is important because it is easy to repeat the study and the study is well tolerated during follow-up. This review summarizes the role of intestinal ultrasound in the detection and follow-up of inflammatory bowel disease.

To assess the effectiveness of colchicine, compared with standard of care, for reducing mortality, admission to intensive care, and use of mechanical ventilation.We performed a systematic review, meta-analysis, and sequential trial analysis. The terms (SARS-CoV-2 OR COVID-19 OR coronavirus) AND (colchicine) were searched in MEDLINE, Scopus, Embase, Cochrane Central Register of Controlled Trials, and preprint repositories (February 2020 to April 2021, extended to June 2021). Risk of bias for randomised controlled trials and observational studies were assessed using the tools RoB 2.0 and ROBINS-I, respectively. We performed subgroup analyses based on study design and sensitivity analyses based on time of colchicine administration.We included six observational studies (1329 patients) and five clinical trials (16,048 patients). All studies but one were conducted in the hospital setting. Colchicine treatment was not associated with a significant decrease in mortality (RR 0.93, 95% CI 0.87 to 1; p=0.06, I2=72%) with a significant subgroup effect (p0.001) depending on the design of the studies. The drug was effective in observational studies (RR 0.57, 95% CI 0.46 to 0.70, p0.001, I2=50%) but not in clinical trials (RR 0.99, 95% CI 0.92 to 1.07, p=0.89, I2=21%). The effect of colchicine on intensive care admissions and the need for mechanical ventilation could not be confirmed. Trial sequential boundaries for cumulative meta-analyses of randomised controlled trials suggested no significant effect on mortality (p=0.182) beyond the optimal information size (13,107 patients).Our results suggest that colchicine treatment has no effect on mortality in hospitalised patients with SARS-CoV-2 infection, and that no further confirmatory clinical trials are needed owing to futility.

The expansion of the COVID‐19 pandemic has been accompanied by numerous reports of chilblain‐like lesions (CLL) in different countries; however, the pathogenesis of these lesions is still unclear. This systematic review and meta‐analysis aimed to assess the prevalence of COVID‐19 (diagnosed using PCR and/or serology) in patients with CLL. We undertook a literature search in PubMed, Embase, and Scopus (to 15 March 2021), including studies that reported on the number of patients with CLL with positive PCR and/or serology for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) or with a clinical suspicion of COVID‐19. Regardless of data heterogeneity, a random‐effects model was used to pool prevalence estimates. The meta‐analysis included 63 original studies, involving 2919 cases of CLL. A subgroup of these patients underwent diagnostic tests for COVID‐19 (PCR: n = 1154, 39.5%; serology: n = 943, 32.3%). The pooled prevalence of COVID‐19 in the overall sample and in the subgroup who were tested for COVID‐19 was, respectively: (i) positive PCR: 2.6% [95% confidence interval (CI) 1.9% to 3.4%] and 5.5% (95% CI, 3.7–7.7%); (ii) positive serology for SARS‐CoV‐2: 7.2% (95% CI, 4.7–10.2%) and 11.8% (95% CI, 7.9–16.3%); and (iii) positive PCR and/or serology, 15.2% (95% CI, 10.4–20.7%) and 7.5% (95% CI, 5.1–10.3%). Altogether, a small proportion of diagnostic tests for SARS‐CoV‐2, both PCR and serologies, show positive results in patients with CLL.

BackgroundTocilizumab (TCZ) is the only biologic drug approved in giant cell arteritis (GCA), based in two clinical trials (CT) (1,2). CT included selected patients who may differ from those of clinical practice (CP). A high proportion of GCA patients treated with TCZ in CT had a newly diagnosed GCA, whereas in CP, most of them are refractory/recurrent GCA (3,4). Although in CT the efficacy of TCZ seems to be similar in patients with newly diagnosed GCA and in patients with refractory/recurrent GCA, in CP it is not documented.ObjectivesTo compare in CP, the effectiveness and safety of TCZ in newly diagnosed vs refractory/recurrent GCA.MethodsMulticentre observational study on 471 GCA patients treated with TCZ. GCA was diagnosed by: a) ACR criteria, and/or b) temporal artery biopsy, and/or c) imaging techniques. A comparative study between patients with newly diagnosed GCA (6 weeks) (according to GiACTA study definitions) (2). Sustained remission was based on EULAR definitions (5).ResultsThe 471 GCA patients were divided into 2 subgroups: a) newly diagnosed GCA (n=91) and b) refractory/recurrent GCA (n=380) (Table 1).Table 1.Main features of patients with newly diagnosed GCA and refractory/recurrent GCA treated with tocilizumab.Newly diagnosed GCA (n=91)Refractory/recurrent GCA (n=380)pBaseline characteristics at TCZ onset Age(years), mean±SD74.3±8.573.3±9.10.35 Sex, female/male (% female)60/31 (66)282/98 (74)0.11 Time from GCA diagnosis to TCZ onset (months), median [IQR]1 [0.5-1]10 [4-24]0.0001 ESR, mm 1st hour, median [IQR]46 [17.5-80.5]27 [10-50]0.02 CRP, mg/dL, median [IQR]2.1 [0.7-8.5]1.3 [0.4-2.8]0.13 Haemoglobin, g/dL, mean±SD12.3±1.512.7±1.50.03 Prednisone dose, mg/day, median [IQR]40 [21.2-50]15 [10-30]Effectiveness and Safety after TCZ onsetFollow-up, (months), median [IQR]15 [6-27.5]22 [11-37]0.004Relevant adverse events, n (%)23 (25)102 (27)0.54Relevant adverse events per 100 patients-year2015NSSerious infections, n (%)13 (14)53 (14)0.49Serious infections per 100 patients-year11.28NSMACES, n (%)0 (0)1 (0.3)-MACES per 100 patients-year00.2-Malignancies n (%)2 (2)3 (0.8)0.99Malignancies per 100 patients-year1.60.5NSAbbreviations: CRP: C-reactive protein;ESR: erythrocyte sedimentation rate;GCA: giant cell arteritis; IQR: interquartile range; IV: intravenous; MACEs: major adverse cardiovascular events; NS: non significant; SC: subcutaneous; SD: standard deviationNo significant differences were observed between both groups in sustained remission, although a greater tendency towards sustained remission is observed in newly diagnosed than in refractory/recurrent GCA patients (Figure 1). The decrease in glucocorticoids dose was faster in the first three months in the newly diagnosed GCA group, but thereafter, was similar in both groups, as well as the appearance of relevant adverse events and serious infections.Figure 1.A) Sustained remission, and B) median prednisone dose required in patients with newly diagnosed GCA and in patients with refractory/recurrent GCA treated with tocilizumab.ConclusionThe effectiveness and safety of TCZ seems to be similar in patients with newly diagnosed GCA and in patients with refractory/recurrent GCA.References[1]Villiger PM, et al. Lancet. 2016; 387:1921-1927. PMID: 26952547[2]Stone JH, et al. N Engl J Med. 2017; 377:317-328. PMID: 28745999[3]Calderón-Goercke M, et al. Semin Arthritis Rheum. 2019; 49: 126-135. PMID: 30655091[4]Calderón-Goercke M, et al. Clin Exp Rheumatol. 2020; 124: S112-119. PMID: 32441643[5]Hellmich B, et al. Ann Rheum Dis. 2020; 79: 19-30. PMID: 31270110AcknowledgementsTocilizumab in Giant Cell Arteritis Spanish Collaborative Group: Juan C. González Nieto (H. Gregorio Marañón), Juan R. de Dios (H.U. Araba), Esther Fernández (H. Clínico Universitario Virgen de la Arrixaca), Isabel de la Morena (H. Clínico Universitario de Valencia), Patricia Moya (H. Sant Pau), Roser Solans i Laqué (H. Valle de Hebrón), Eva Pérez Pampín (H.U. de Santiago), José L. Andréu (H.U. Puerta de Hierro), Marcelino Revenga (H. Ramón y Cajal), Juan P. Baldivieso Achá (H. U. de La Princesa), Eztizen Labrador (H. San Pedro), Andrea García-Valle (Complejo Asistencial Universitario de Palencia), Adela Gallego (Complejo Hospitalario Universitario de Badajoz), Carlota Iñíguez (H.U. Lucus Augusti), Cristina Hidalgo (Complejo Asistencial Universitario de Salamanca), Noemí Garrido-Puñal (H. Virgen del Rocío), Ruth López-González (Complejo Hospitalario de Zamora), José A. Román-Ivorra (H.U. y Politécnico La Fe), Sara Manrique (H. Regional de Málaga), Paz Collado (H.U. Severo Ochoa), Enrique Raya (H. San Cecilio), Valvanera Pinillos (H. San Pedro), Francisco Navarro (H. General Universitario de Elche), Alejandro Olivé-Marqués (H. Trías i Pujol), Francisco J. Toyos (H.U. Virgen Macarena), María L. Marena Rojas (H. La Mancha Centro), Antoni Juan Más (H.U. Son Llàtzer), Beatriz Arca (H.U. San Agustín), Carmen Ordás-Calvo (H. Cabueñes), María D. Boquet (H. Arnau de Vilanova), Noelia Álvarez-Rivas (H.U. Lucus Augusti), María L. Velloso-Feijoo (H.U. de Valme), Cristina Campos (H. General Universitario de Valencia), Íñigo Rúa-Figueroa (H. Doctor Negrín), Antonio García (H. Virgen de las Nieves), Carlos Vázquez (H. Miguel Servet), Pau Lluch (H. Mateu Orfila), Carmen Torres (Complejo Asistencial de Ávila), Cristina Luna (H.U. Nuestra Señora de la Candelaria), Elena Becerra (H.U. de Torrevieja), Nagore Fernández-Llanio (H. Arnáu de Vilanova), Arantxa Conesa (H.U. de Castellón), Eva Salgado (Complejo Hospitalario Universitario de Ourense).Disclosure of InterestsJulio Sanchez-Martin: None declared, Javier Loricera: None declared, Clara Moriano: None declared, Santos Castañeda: None declared, J. Narváez: None declared, Vicente Aldasoro: None declared, Olga Maiz: None declared, Rafael Melero: None declared, Ignacio Villa-Blanco: None declared, Paloma Vela-Casasempere: None declared, Susana Romero-Yuste: None declared, Jose Luis Callejas-Rubio: None declared, Eugenio de Miguel: None declared, E. Galíndez-Agirregoikoa: None declared, Francisca Sivera: None declared, Carlos Fernández-López: None declared, Carles Galisteo: None declared, Iván Ferraz-Amaro: None declared, Lara Sanchez-Bilbao: None declared, Monica Calderón-Goercke: None declared, Jose Luis Hernández Hernández: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Grant/research support from: Abbvie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Grant/research support from: Abbvie, MSD and Roche

BackgroundLarge vessel involvement in Giant Cell Arteritis (GCA), especially the aorta and/or its main branches, is frequent. Tocilizumab (TCZ) has shown efficacy and safety in GCA and other large-vessel vasculitis (1-4).ObjectivesTo assess the efficacy and safety of TCZ in GCA patients with involvement of the aorta and/or its main branches.MethodsMulticenter observational study of 196 patients with GCA and involvement of the aorta and/or its major branches treated with TCZ. GCA was diagnosed by: a) ACR criteria, and/or b) temporal artery biopsy, and/or c) imaging techniques. The presence of aortitis was performed by imaging techniques, mainly PET, and A-MRI.Maintained remission was considered according to EULAR definitions (5).ResultsThe main features of the 196 patients are showed in Table 1. Polymyalgia rheumatica, constitutional syndrome and headache were the most frequent clinical manifestations at TCZ onset. At 6 months after starting TCZ, 20% of the patients reached a sustained remission, that was progressively increasing. (Figure 1). A corticosteroid-sparing effect was observed from month 1 of TCZ onset (Figure 1). Relevant adverse events were observed in 12 per 100 patients-year, documenting serious infections in 4.8 per 100 patients-year (Table 1).Table 1.Main features of 196 GCA patients with involvement of the aorta and/or its main branches treated with TCZ.GCA (n=196)Features at TCZ onsetAge(years), mean±SD71.3±9.5Sex, female/male (% female)148/48 (75)Time from GCA diagnosis to TCZ onset (months), median [IQR]7 [2-18.25]Systemic manifestations, n (%)Fever, n (%)24 (12)Constitutional syndrome, n (%)87 (44)PmR, n (%)131 (67)Ischaemic manifestations, n (%)Visual involvement, n (%)16 (8)Headache, n (%)74 (38)Jaw claudication, n (%)27 (14)Laboratory dataESR, mm 1st hour, median [IQR]32 [14-54]CRP, mg/dL, median [IQR]1.5 [0.6-3.2]Prednisone dose, mg/day, median [IQR]15 [10-30]Safety after TCZ onsetRelevant adverse events, per 100 patients-year12Serious infections, per 100 patients-year4.8Figure 1.A) Sustained remission, and B) median prednisone dose required in GCA patients with aortitis treated with tocilizumabConclusionTCZ seems to be effective and relatively safe in GCA patients with involvement of the aorta and/or its main branches.References[1]Calderón-Goercke M, et al. Semin Arthritis Rheum. 2019; 49: 126-135. PMID: 30655091[2]Loricera J, et al. Clin Exp Rheumatol. 2016; 34: S44-53. PMID: 27050507[3]Loricera J, et al. Clin Exp Rheumatol. 2015; 33: S19-31. PMID: 25437450[4]Prieto-Peña D, et al. Ther Adv Musculoskelet Dis. 2021; 13: 1759720X211020917. PMID: 34211589[5]Hellmich B, et al. Ann Rheum Dis. 2020; 79: 19-30. PMID: 31270110Disclosure of InterestsLara Sanchez-Bilbao: None declared, Javier Loricera Speakers bureau: from Roche, Novartis, UCB Pharma, Celgene, and Grünenthal., Rafael Melero: None declared, Santos Castañeda Speakers bureau: UAM-Roche, EPID- Future chair, Department of Medicine, Universidad Autónoma de Madrid, Madrid, Spain., Clara Moriano: None declared, Iván Ferraz-Amaro: None declared, J. Narváez: None declared, Vicente Aldasoro: None declared, Olga Maiz: None declared, Ignacio Villa-Blanco: None declared, Paloma Vela-Casasempere: None declared, Susana Romero-Yuste: None declared, Jose Luis Callejas-Rubio: None declared, Eugenio de Miguel: None declared, E. Galíndez-Agirregoikoa: None declared, Francisca Sivera: None declared, Carlos Fernández-López: None declared, Carles Galisteo: None declared, Julio Sanchez-Martin: None declared, Monica Calderón-Goercke: None declared, J. Luis Hernández: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, and MSD., Grant/research support from: AbbVie, MSD, Jansen, and Roche,, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD., Grant/research support from: Abbvie, MSD, and Roche

BackgroundTocilizumab (TCZ) has shown to be effective for large vessel vasculitis including giant cell arteritis (GCA) and Takayasu arteritis (TAK) (1-5). However, LVV-GCA and TAK show different demographic and clinical features that may influence on TCZ therapeutic response.ObjectivesTo compare the effectiveness of TCZ in patients with LVV-GCA and patients with TAK.MethodsObservational multicenter study of patients with LVV-GCA and TAK who received TCZ. Outcome variables were: a) proportion of patients who achieved complete clinical improvement along with normalization of laboratory markers (CRP ≤0.5mg/dL and/or ESR ≤ 20 mm/1st hour) at 12 months b) complete improvement in imaging techniques. A comparative study between patients with LVV-GCA and TAK was performed.ResultsWe evaluated 70 LVV-GCA and 57 TAK patients who received TCZ. Main clinical and demographic characteristic are described in Table 1. Patients with TAK were younger, had longer disease duration, had received more commonly previous biologic therapy and were receiving higher doses of prednisone at baseline. TCZ intravenous administration was more common in TAK patients (80.7% vs 48.6%; pTable 1.LVV-GCA (n=70)TAK (n=57)pGeneral featuresAge (years), mean ± SD67.2 ± 10.540.5 ± 16.3< 0.01Sex (female), n (%)51 (72.9)49 (86)0.07Disease evolution before TCZ onset (months), median [IQR]5 [2-15]12 [3-37]Baseline laboratory parametersESR (mm/1st hour), median [IQR]32 [12.5-54.7]31 [10-52]0.82CRP (mg/dL), median [IQR]1.4 [0.5-2.4]1.4 [0.5-3.5]0.41Baseline prednisone dose (mg/day), median [IQR]15 [10-20]30 [15-50]< 0.01Previous therapyConventional DMARDs, n(%)45 (64.3)44(77.2)0.51Biologic therapy, n (%)0(0)12 (21.1)TCZ therapyIntravenous, n (%)34 (48.6)46 (80.7)< 0.01Combined with MTX, n(%)24 (34.3)24 (42.1)0.37Follow-up time after TCZ onset, median [IQR]20 [10-36]18 [7-41]0.73Complete clinical improvement and ESR/CRP normalization at 12 months, n/N (%)35/47 (74.4)30/39 (76.9)0.79Complete improvement in imaging techniques, n/N(%)7/37 (18.9)8/38 (21.1)0.85CRP: C-reactive protein; DMARDs: Disease-modifying anti-rheumatic drugs ESR: erythrocyte sedimentation rate; GCA: giant cell arteritis; IQR: interquartile range; LVV: large vessel; MTX: methotrexate; n: Number of patients; N: total number of patients: TCZ: tocilizumab; TAK:takayasuFigure 1.ConclusionThe effectiveness of TCZ was similar in patients with LVV-GCA and TAK, despite a more refractory disease in TAK patients. A discordance between clinical and imaging activity improvement was observed in both LVV-GCA and TAK, as reported in previous studies (3).References[1]Calderón-Goercke M, et al. Semin Arthritis Rheum 2019; 49:126-35. https://doi.org/10.1016/j.semarthrit.2019.01.003[2]Prieto-Peña D et al. Ther Adv Musculoskelet Dis. 2021;13:175. PMID: 34211589.[3]Prieto Peña D et al. Clin Exp Rheumatol. 2021;39 Suppl 129:69-75. PMID: 33253103.[4]González-Gay MA, et al. Expert Opin Biol Ther. 2019;19:65-72. doi: 10.1080/14712598.2019.1556256.[5]Prieto-Peña D, et al. Semin Arthritis Rheum. 2019;48(4):720-727. doi: 10.1016/j.semarthrit.2018.05.007Disclosure of InterestsNone declared

BackgroundEpidemiological information on Giant Cell Arteritis (GCA) comes mainly from the Scandinavian countries of northern Europe, which show a higher incidence than the countries of southern Europe. GCA clinical manifestations can be divided into cranial, extracranial, and general syndrome.ObjectivesIn a large series of GCA from Spain, we studied a) the incidence of GCA, b) clinical manifestations, and c) comorbidities at the time of disease diagnosis.MethodsARTESER is a retrospective epidemiological observational study of GCA promoted by the Spanish Society of Rheumatology in which 26 hospitals participate. The inclusion criteria were: all new patients diagnosed with GCA by a) ACR criteria, b) positive diagnostic test (temporal artery biopsy, temporal artery ultrasound or other relevant imaging techniques) and/or c) investigator’s clinical judgment. The patient recruitment period ranged from June 1, 2013 to March 29, 2019. The overall incidence of GCA per 100,000 people ≥50 years for the whole period and the mean annual incidence were evaluated. The clinical variables were collected by reviewing the patient’s medical history.Results1675 patients were included. The average annual incidence rate was 7.42 (95% CI: 6.57-8.27). All the cases were older than 50 years, and the age group with the highest annual incidence was that of 80 to 84 years, where it reached a value of 22.63 (95% CI: 22.04 -23.22). The mean annual incidence is higher in women than in men 10.07 (95% CI: 8.74-11.55) vs 4.81 (95% CI 3.84-5.93) (Table 1).Table 1.General characteristics, comorbidities and clinical manifestationsEpidemiologic, demographic and diagnosisMenWomenTotalGender, n (%)497 (29.7)1178 (70.3)1675Incidence annual rate (95% CI)4.81 (3.84-5.93)10.07 (8.74-11.55)7.42 (6.57-8.27)Age at diagnosis, years, mean (SD)76.9 (8.3)76.9 (8.0)76.9 (8.1)Diagnosis only by ACR Criteria89 (17.91)266 (22.58)355 (21.19)Diagnosis only with objective tests73 (14.69)140 (11.88)213 (12.72)Diagnosis ACR criteria + diagnosis objective tests311 (62.58)734 (62.31)1045 (62.39)Diagnosis by clinical judgment24 (4.8)38 (3.2)62 (3.7)Comorbidities at diagnosisArterial hypertension, n (%)330 (66.8)749 (63.7)1079 (64.6)Dyslipidemia, n (%)238 (48.3)563 (47.9)801 (48.0)Cranial clinical manifestationsNew-onset headache, n (%)382 (76.9)955 (81.1)1337 (79.9)Visual Clinic, n (%)194 (39.0)411 (34.9)605 (36.1)Extracranial manifestations and general syndromePolymyalgia rheumatica, n (%)178 (35.8)521 (44.3)699 (41.8)Asthenia, n (%)239 (48.1)634 (53.9)873 (52.2)Analysis at diagnosisErythrocyte sedimentation rate mm/h, mean (SD)72.3 (34.7)77.4 (33.0)75.9 (33.6)The principal clinical characteristics of the population is shown in Table 1, the mean age at diagnosis was 76.9±8.1 years, 1178 (70.3%) were women. 1045 patients (62.39%) had ACR criteria and some positive objective test, 355 patients (21.9%) presented only ACR criteria and 213 (12.72%) only had a positive diagnostic test; 62 (3.7%) of the patients underwent diagnosis based on clinical judgment. The more frequent comorbidity was arterial hypertension (n=1079; 64.6%), followed by dyslipidemia (n=801, 48%). The predominant cranial manifestation was headache (n= 1337; 79.9%) and 605 patients experienced visual symptoms (36.1%). Polymyalgia rheumatica (n=699; 41.8%) and asthenia (n=837; 52.2%) were the most frequent extracranial and general syndrome manifestation, respectively. Regarding laboratory parameters, the most characteristic data was the increase of ESR (75.9±33.6 mm/1st h).ConclusionThe mean annual incidence of GCA in Spain, 7.42 (95% CI: 6.57-8.27), is lower than that of the Scandinavian countries. It is higher in people older than 80 years. More than 60% of the patients met the ACR criteria and had a positive diagnostic test. Cranial manifestations constituted the most clinical features. The most frequent clinical manifestations are cranial. Up to a third of patients had visual manifestations.AcknowledgementsThis study has been funded by ROCHE Farma. The funder has not participated in the design, analysis, or interpretation of the resultsDisclosure of InterestsNone declared

BackgroundLarge-vessel vasculitis are characterized by the wall inflammation of the involved vessels, which can be detected by imaging tools (1-3). Ultrasound (US) is one of the most commonly used tools for the diagnosis of giant cell arteritis (GCA), especially in patients with a cranial phenotype. Tocilizumab (TCZ) has shown efficacy in large-vessel vasculitis (LVV) including GCA (4,5). However, the improvement objectified by imaging techniques such as US after TCZ therapy is poorly documented.ObjectivesTo assess the effectiveness of TCZ improving the wall vessel inflammation by US.MethodsObservational, multicenter study of 26 GCA patients treated with TCZ. GCA was diagnosed according to: a) ACR criteria, and/or b) biopsy of temporal artery, and/or c) presence of signs of vessel wall inflammation by US, defined by the presence of halo sign. In all the cases a baseline US and in the follow-up was mandatory.Patients were divided into two subgroups: a) with, and b) without signs of improvement (partial or total) in the follow-up US.ResultsWe studied 26 patients (19 women/7 men; mean age, 76.3±9.7 years). Main clinical features of GCA with and without US improvement are shown in Table 1. We found no significant differences in any of the variables studied between the two groups.Table 1.Main features of 27 GCA patients treated with tocilizumab followed by Ultrasound (US).With US improvement (n=21)Without US improvement (n=5)pBaseline characteristics at TCZ onsetGeneral characteristicsAge(years), mean±SD77.3±8.972.2±12.90.270Sex, female/male (% female)17/4 (80,95)2/3 (40)0.101Time from GCA diagnosis to TCZ onset (months), median [IQR]6 [3-9]3 [1-6]0.452Systemic manifestations, n (%)Fever, n (%)1/21 (4.76)1/5 (20)0.354Constitutional syndrome, n (%)10/21 (47.62)2/5 (40)0.999PmR, n (%)11/21 (52.38)1/5 (20)0.330Ischaemic manifestations, n (%)Visual involvement, n (%)1/21 (4.76)1/5 (20)0.354Headache, n (%)15/21 (71.43)5/5 (100)0.298Jaw claudication, n (%)4/15 (26.67)¼ (25)0.999Laboratory dataESR, mm 1st hour, median [IQR]33 [22-49]55 [54-80]0.216CRP, mg/dL, median [IQR]1.5 [0.7-6.7]3.8 [1-4.2]0.948Prednisone dose, mg/day, median [IQR]13.7 [10-30]30 [12.5-30]0.505Time from TCZ onset and follow-up US (months)3.9±3.63.1±2.10.456After TCZ onset, 21 of 26 patients (80.7%) showed US signs of improvement (12 complete, 9 partial). In 4 out of 5 patients in whom there was no improvement in US findings, clinical improvement was observed at first month after starting TCZ.ConclusionTCZ seems to be effective controlling GCA including vascular involvement detected by US. This improvement can be seen by follow-up US, especially when performed at least 3 months after TCZ onset.References[1]Loricera J, et al. Rev Esp Med Nucl Imagen Mol. 2015; 34: 372-7. PMID: 26272121[2]Loricera J, et al. Clin Exp Rheumatol. 2015; 33: S19-31. PMID: 25437450[3]Prieto-Peña D, et al. Ther Adv Musculoskelet Dis. 2021; 13: 1759720X211020917. PMID: 34211589[4]Martínez-Rodríguez I, et al. Semin Arthritis Rheum. 2018; 47: 530-537. PMID: 28967430[5]Prieto-Peña D, et al. Semin Arthritis Rheum. 2019; 48: 720-727. PMID: 29903537AcknowledgementsTocilizumab in Giant Cell Arteritis Spanish Collaborative Group: Juan C. González Nieto (H. Gregorio Marañón), Juan R. de Dios (H.U. Araba), Esther Fernández (H. Clínico Universitario Virgen de la Arrixaca), Isabel de la Morena (H. Clínico Universitario de Valencia), Patricia Moya (H. Sant Pau), Roser Solans i Laqué (H. Valle de Hebrón), Eva Pérez Pampín (H.U. de Santiago), José L. Andréu (H.U. Puerta de Hierro), Marcelino Revenga (H. Ramón y Cajal), Juan P. Baldivieso Achá (H. U. de La Princesa), Eztizen Labrador (H. San Pedro), Andrea García-Valle (Complejo Asistencial Universitario de Palencia), Adela Gallego (Complejo Hospitalario Universitario de Badajoz), Carlota Iñíguez (H.U. Lucus Augusti), Cristina Hidalgo (Complejo Asistencial Universitario de Salamanca), Noemí Garrido-Puñal (H. Virgen del Rocío), Ruth López-González (Complejo Hospitalario de Zamora), José A. Román-Ivorra (H.U. y Politécnico La Fe), Sara Manrique (H. Regional de Málaga), Paz Collado (H.U. Severo Ochoa), Enrique Raya (H. San Cecilio), Valvanera Pinillos (H. San Pedro), Francisco Navarro (H. General Universitario de Elche), Alejandro Olivé-Marqués (H. Trías i Pujol), Francisco J. Toyos (H.U. Virgen Macarena), María L. Marena Rojas (H. La Mancha Centro), Antoni Juan Más (H.U. Son Llàtzer), Beatriz Arca (H.U. San Agustín), Carmen Ordás-Calvo (H. Cabueñes), María D. Boquet (H. Arnau de Vilanova), Noelia Álvarez-Rivas (H.U. Lucus Augusti), María L. Velloso-Feijoo (H.U. de Valme), Cristina Campos (H. General Universitario de Valencia), Íñigo Rúa-Figueroa (H. Doctor Negrín), Antonio García (H. Virgen de las Nieves), Carlos Vázquez (H. Miguel Servet), Pau Lluch (H. Mateu Orfila), Carmen Torres (Complejo Asistencial de Ávila), Cristina Luna (H.U. Nuestra Señora de la Candelaria), Elena Becerra (H.U. de Torrevieja), Nagore Fernández-Llanio (H. Arnáu de Vilanova), Arantxa Conesa (H.U. de Castellón), Eva Salgado (Complejo Hospitalario Universitario de Ourense).Disclosure of InterestsJulio Sanchez-Martin: None declared, Javier Loricera: None declared, Lara Sanchez-Bilbao: None declared, Eugenio de Miguel: None declared, Rafael Melero: None declared, E. Galíndez-Agirregoikoa: None declared, J. Narváez: None declared, Carles Galisteo: None declared, Juan Carlos Nieto González: None declared, Patricia Moya: None declared, Eztizen Labrador-Sánchez: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Grant/research support from: Abbvie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Grant/research support from: Abbvie, MSD and Roche

BackgroundPositron emission tomography (PET) is one of the tools available for the diagnosis of extracranial large-vessel vasculitis (1-5). Tocilizumab (TCZ) has shown efficacy in large-vessel vasculitis (LVV) including GCA. However, the improvement objectified by imaging techniques after TCZ therapy in extracranial GCA patients is controversial.ObjectivesTo assess the effectiveness of TCZ improving the wall vessel inflammation by PET in GCA patients with large-vessel involvement.MethodsObservational, multicenter study of 101 GCA patients treated with TCZ. GCA was diagnosed according to: a) ACR criteria, and/or b) biopsy of temporal artery, and/or c) presence of signs of vessel wall inflammation by PET, defined by the presence of vascular wall uptake of Fluorodeoxyglucose (FDG). Patients were divided into two subgroups: a) with, and b) without signs of improvement (partial or total) in the follow-up PET.ResultsWe studied 101 patients (74 women/27 men; mean age 69.7±9.3 years). Main clinical features of GCA with and without PET improvement are shown in Table 1. The group of patients which experienced PET improvement was older and was receiving higher doses of corticosteroids at TCZ onset.Table 1.Main features of 101 GCA patients treated with tocilizumab and with presence of signs of vessel wall inflammation by PET.With PET improvement (n=88)Without PET improvement (n=13)pBaseline characteristics at TCZ onsetGeneral characteristicsAge(years), mean±SD70.6±9.163.8±9.20.014Sex, female/male (% female)67/21(76)7/6 (54)0.103Time from GCA diagnosis to TCZ onset (months), median [IQR]11 [4-24.2]4 [2-6]0.102Systemic manifestations, n (%)Fever, n (%)5 (6)2 (15)0.225Constitutional syndrome, n (%)36 (41)4 (31)0.466PmR, n (%)53 (60)9 (10)0.761Ischaemic manifestations, n (%)Visual involvement, n (%)2 (2)1 (1)0.342Headache, n (%)30 (34)3 (23)0.538Jaw claudication, n (%)8 (9)0 (0)0.592Laboratory dataESR, mm 1st hour, median [IQR]38.0 ± 26.213.54 ± 9.90.001CRP, mg/dL, median [IQR]1.5 [0.7-2.4]1 [0.5-1.7]0.179Prednisone dose, mg/day, median [IQR]40.3 ± 19.421.9 ± 12.70.001Time from TCZ onset and follow-up PET (months)13.1±8.010.1±5.30.446ConclusionTCZ seems to be effective controlling GCA including vascular involvement detected by PET. However, the improvement observed by PET is most often partial, and rarely complete.Figure 1.Improvement by PET according to the time of the test.References[1]Loricera J, et al. Rev Esp Med Nucl Imagen Mol. 2015; 34: 372-7. PMID: 26272121[2]Loricera J, et al. Clin Exp Rheumatol. 2015; 33: S19-31. PMID: 25437450[3]Prieto-Peña D, et al. Ther Adv Musculoskelet Dis. 2021; 13: 1759720X211020917. PMID: 34211589[4]Martínez-Rodríguez I, et al. Semin Arthritis Rheum. 2018; 47: 530-537. PMID: 28967430[5]Prieto-Peña D, et al. Semin Arthritis Rheum. 2019; 48: 720-727. PMID: 29903537AcknowledgementsTocilizumab in Giant Cell Arteritis Spanish Collaborative Group: Juan C. González Nieto (H. Gregorio Marañón), Juan R. de Dios (H.U. Araba), Esther Fernández (H. Clínico Universitario Virgen de la Arrixaca), Isabel de la Morena (H. Clínico Universitario de Valencia), Patricia Moya (H. Sant Pau), Roser Solans i Laqué (H. Valle de Hebrón), Eva Pérez Pampín (H.U. de Santiago), José L. Andréu (H.U. Puerta de Hierro), Marcelino Revenga (H. Ramón y Cajal), Juan P. Baldivieso Achá (H. U. de La Princesa), Eztizen Labrador (H. San Pedro), Andrea García-Valle (Complejo Asistencial Universitario de Palencia), Adela Gallego (Complejo Hospitalario Universitario de Badajoz), Carlota Iñíguez (H.U. Lucus Augusti), Cristina Hidalgo (Complejo Asistencial Universitario de Salamanca), Noemí Garrido-Puñal (H. Virgen del Rocío), Ruth López-González (Complejo Hospitalario de Zamora), José A. Román-Ivorra (H.U. y Politécnico La Fe), Sara Manrique (H. Regional de Málaga), Paz Collado (H.U. Severo Ochoa), Enrique Raya (H. San Cecilio), Valvanera Pinillos (H. San Pedro), Francisco Navarro (H. General Universitario de Elche), Alejandro Olivé-Marqués (H. Trías i Pujol), Francisco J. Toyos (H.U. Virgen Macarena), María L. Marena Rojas (H. La Mancha Centro), Antoni Juan Más (H.U. Son Llàtzer), Beatriz Arca (H.U. San Agustín), Carmen Ordás-Calvo (H. Cabueñes), María D. Boquet (H. Arnau de Vilanova), Noelia Álvarez-Rivas (H.U. Lucus Augusti), María L. Velloso-Feijoo (H.U. de Valme), Cristina Campos (H. General Universitario de Valencia), Íñigo Rúa-Figueroa (H. Doctor Negrín), Antonio García (H. Virgen de las Nieves), Carlos Vázquez (H. Miguel Servet), Pau Lluch (H. Mateu Orfila), Carmen Torres (Complejo Asistencial de Ávila), Cristina Luna (H.U. Nuestra Señora de la Candelaria), Elena Becerra (H.U. de Torrevieja), Nagore Fernández-Llanio (H. Arnáu de Vilanova), Arantxa Conesa (H.U. de Castellón), Eva Salgado (Complejo Hospitalario Universitario de Ourense).Disclosure of InterestsJulio Sanchez-Martin: None declared, Javier Loricera: None declared, Santos Castañeda: None declared, Clara Moriano: None declared, J. Narváez: None declared, Vicente Aldasoro: None declared, Olga Maiz: None declared, Rafael Melero: None declared, Ignacio Villa-Blanco: None declared, Paloma Vela-Casasempere: None declared, Susana Romero-Yuste: None declared, Jose Luis Callejas-Rubio: None declared, Eugenio de Miguel: None declared, E. Galíndez-Agirregoikoa: None declared, Francisca Sivera: None declared, Carlos Fernández-López: None declared, Carles Galisteo: None declared, Iván Ferraz-Amaro: None declared, Lara Sanchez-Bilbao: None declared, Monica Calderón-Goercke: None declared, Jose Luis Hernández Hernández: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Grant/research support from: Abbvie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Grant/research support from: Abbvie, MSD and Roche

To explore the sensitivity to change in power Doppler (PD) enthesitis in active spondyloarthritis (SpA) and psoriatic arthritis (PsA) patients.This was a longitudinal study in patients with SpA and PsA with active disease [patients starting or switching to biological disease-modifying anti-rheumatic drugs (bDMARDs)]. The MAdrid Sonographic Enthesitis Index (MASEI) was performed at baseline and at 3 and 6 month visits. The MASEI and Outcome Measures in Rheumatology (OMERACT) PD enthesitis definitions were checked. Reliability analysis among three readers was performed with ultrasound (US)-recorded videos.US examinations of 25 patients were included; 16 (64%) had SpA and nine (36%) PsA. The median (interquartile range, IQR) age was 49 (41-61) years, and 13 patients (52%) were female. The median (IQR) 28-joint Disease Activity Score of 3.6 (2.3-4.2), Bath Ankylosing Spondylitis Disease Activity Index of 6.7 (6.1-7.4), and C-reactive protein value of 8.2 (1.6-20) reflected moderate to high disease activity at baseline. Both MASEI and OMERACT PD enthesitis improved significantly at 3 and 6 month follow-up (p 0.05) and showed sensitivity to change (standard error of measurement = 0.47 and 0.61, respectively). Improvement in clinical activity outcomes was significantly associated with decreases in MASEI and OMERACT PD enthesitis counts (p 0.05). The MASEI and OMERACT PD definitions had excellent reliability (kappa = 0.918 and 0.865, respectively).PD enthesitis significantly improved at 3 and 6 month follow-up in patients undergoing bDMARD therapy. Both MASEI and OMERACT PD US enthesitis reflect response to treatment.

Resumen El uso de contrastes iodados puede causar nefrotoxicidad. Actualmente se cuestiona que los contrastes sean los responsables exclusivos del dano renal, ya que en la mayoria de los casos coexisten otras causas potenciales de fracaso renal. Con los contrastes actuales de baja osmolaridad e isoosmolares, la incidencia de nefropatia por contraste se estima que es inferior al 1% en la poblacion de bajo riesgo; pero puede incrementarse hasta el 37% en pacientes que reciben contraste por via intraarterial y/o que presentan insuficiencia renal con filtrado glomerular estimado inferior a 30 ml/min/1,73 m2. Para minimizar el riesgo de nefrotoxicidad se recomienda administrar la menor cantidad posible de contraste y asegurar una adecuada expansion de volumen mediante la infusion de solucion salina 0,9%.

Resumen Introduccion El objetivo es comparar el rendimiento de la secuencia resonancia magnetica (RM) y biopsia transrectal «cognitiva» (BTRCog) frente a la biopsia transrectal clasica (BTRCl) en pacientes con al menos una biopsia de prostata (BP) negativa. Material y metodo Analisis retrospectivo de 205 pacientes con al menos una BP negativa. A 144 (70,2%) pacientes se les realizo antes de la biopsia una RM y a 61 (29,8%) no. Los nodulos se clasificaron segun la clasificacion PI-RADS v2 agrupando pZa, pZpl y pZpm como zona periferica (ZP), Tza, Tzp y CZ como zona transicional (ZT) y areas AS como zona anterior (ZA). A los pacientes con RM se les realizo BTRCog. A los pacientes sin RM se les realizo una BTRCl de la ZP y de la ZT. Comparacion de variables cualitativas con test de la chi2 y de cuantitativas con t de Student. Analisis multivariante (regresion logistica) para identificar variables predictoras. Resultados La mediana de edad fue 68 (IQR 62-72%) anos, de PSA 8,3 (IQR 6,2-11,7) ng/ml y del numero de biopsias previas fue 1 (IQR 1-2). En 169 (82,4%) el tacto rectal (TR) fue normal, mientras que en 36 (17,6%) sospechoso (cT2a-b en 34 y cT2c en 2). La mediana del volumen prostatico (VP) fue de 48 (IQR 38-65) cc. Existio diferencia en el PSAD (p = 0,03) entre ambos grupos. En la ETR se identifico nodulo hipoecoico en 8 (13,1%) pacientes con BTRCl y en 62(43,1%) (p = 0,0001) con BTRCog. La mediana de cilindros extraidos en BTRCl fue 10 (IQR 10-10) y en el grupo BTRCog fue 11 (IQR 9-13) (p = 0,75). Se diagnostico cancer en 74 (36,1%) pacientes. En BTRCl 10 (16,4%) y en BTRCog 64 (44,4%) (p = 0,0001). Los tumores diagnosticados fueron clasificados: ISUP-1: 34 (45,9%), ISUP-2: 21 (28,4%), ISUP-3: 9 (12,2%), ISUP-4: 7 (9,5%), ISUP-5: 3 (4,1%). No existieron diferencias (p = 0,89). La mediana de cilindros afectados en BTRCl fue 1 (IQR 1-5) frente a 2 (IQR 1-4) en el grupo BTRCog (p = 0,93). Variables predictoras independientes de cancer: edad (OR = 12,05, p = 0,049). TR sospechoso (OR = 2,64, p = 0,04), nodulo hipoecoico en ecografia (OR = 2,20, p = 0,03) y la secuencia RM + BTRCog (OR = 3,49, p = 0,003). Conclusiones La secuencia RMNmp + BTRCog en pacientes con al menos una BP previa negativa multiplica casi por 3,5 (OR = 3,49) la probabilidad de diagnosticar un cancer frente a la BTRCl.

Resumen Introduccion Evaluacion de la efectividad de la biopsia cognitiva (BC) en los pacientes con sospecha clinica de cancer de prostata (caP) y al menos una biopsia negativa (BTR). Material y metodo Analisis retrospectivo de 144 pacientes con al menos una BTR y una resonancia magnetica nuclear (RMN) previa. Los nodulos de la RMN se clasificaron segun la clasificacion PI-RADS v2 agrupando pZa, pZpl y pZpm como zona periferica (ZP), Tza, Tzp y CZ como zona transicional (ZT) y areas AS como zona anterior (ZA). Se indico biopsia en nodulos ≥ PI-RADS 3. Se llevo a cabo analisis uni y multivariante (regresion logistica) tratando de identificar variables relacionadas con tumor en biopsia de PI-RADS 3. Resultados La mediana de edad fue de 67 (IQR: 62-72) anos, la de PSA 8,2 (IQR: 6,2-12) ng/ml. Se identifico nodulo en la RMN en la ZP en 97 (67,4%) casos, en la ZT en 29 (20,1%) casos y en ZA en 41 (28,5%) casos. Se diagnostico caP en la biopsia en 64 (44%) pacientes. En PI-RADS 3 se obtuvo un 17,5% (7/40) de cancer, PI-RADS 4 un 47,3% (35/73) y en los PI-RADS 5 un 73,3% (22/29) (p = 0,0001). Analisis multivariable con variables que pudieran influir en el resultado de la biopsia en pacientes con PI-RADS 3: ninguno (edad, PSA, numero de biopsias previas, tacto rectal, PSAD, volumen prostatico ni numero de cilindros extraidos) se comporto como factor predictor independiente de tumor. Conclusiones El rendimiento diagnostico de la BC en pacientes con al menos una biopsia previa negativa fue del 44% incrementandose segun el grado de PI-RADS, siendo en PI-RADS 3 bajo. No se identifico ninguna variable clinica predictora de caP en pacientes con PI-RADS 3.

Introduction Evaluation of the effectiveness of cognitive biopsy (CB) in patients with clinical suspicion of prostate cancer (PC), and at least one negative biopsy (TRB). Material and method Retrospective study of 144 patients with at least one previous TRB and magnetic resonance imaging (MRI). The MRI nodules were classified based on PI-RADS v2 grouping pZa, pZpl and pZpm as the peripheral zone (PZ), Tza, Tzp and CZ as the transitional zone (TZ), and the AS zones as the anterior zone (AZ). A biopsy was indicated for nodules ≥PI-RADS 3. Uni and multivariate analysis was undertaken (logistic regression) to identify variables relating to a PI-RADS 3 tumour on biopsy. Results The median age was 67 (IQR: 62–72) years, the median PSA was 8.2 (IQR: 6.2–12) ng/ml. A nodule was identified on MRI in the PZ in 97 (67.4%) cases, in the TZ in 29 (20.1%), and in the AZ in 41 (28.5%). PC was diagnosed on biopsy in 64 (44%) patients. The cancer rate in the PI-RADS 3 lesions was 17.5% (7/40), in the PI-RADS 4 47.3% (35/73), and in the PI-RADS 5 lesions it was 73.3% (22/29) (p = 0.0001). Multivariable analysis with variables that could influence the biopsy result in patients with PI-RADS 3: none (age, PSA, number of previous biopsies, rectal examination, PSAD, prostate volume or number of extracted cylinders) behaved as an independent tumour predictor. Conclusions The diagnostic performance of CB in patients with at least one previous negative biopsy was 44%, increasing according to the PI-RADS grade, and low in PI-RADS 3. No clinical variable predictive of cancer was found in patients with PI-RADS 3.

In many parts of the world, especially in arid or semi-arid areas, they find drinking water in the subsoil. One way to reach it, it is through small horizontal tunnels (Qanat) built on the mountain using explosives. Civil engineers must design projects where they estimate the budget necessary to undertake the work, taking into account the amount of explosives needed, number of blasts, duration of the civil work and powder factor among other data. However, there is not artificial intelligence-based models that help to forecast the amount of explosive needed to drill a tunnel. In this work, a hybrid regression model based on support vector machine (SVM) and particle swarm optimization (PSO) trained with real data (types of lithologies, geomechanical characteristics of the rocks and the amount of explosives used by engineers based on their previous experiences) obtained from a volcanic groundwater tunnel driving in the island of Tenerife (Spain), is proposed to predict the advance, the amount of explosives, the number of blasts and the powder factor in new tunnels or expansion of existing ones. The results show that a new, simpler regression model has been obtained that reproduces the experimental data and it will reduce the effort of the engineers in the study of a new tunnel driving work.

BackgroundPolymyalgia rheumatica (PMR) can be associated with giant cell arteritis (GCA), even in the absence of clinical suspicions of vasculitis. In addition, some studies have shown an association of PMR with the predominantly large vessel involvement.ObjectivesThe objective of our study was to assess the presence of subclinical GCA in patients with PMR and to compare its pattern of vascular involvement to patients with classical GCA.MethodsEight rheumatology European centers participated in the study. Cohort A represented consecutive newly diagnosed patients with PMR who fulfilled the 2012 EULAR/ACR Provisional Classification Criteria for Polymyalgia Rheumatica2 and had no symptoms or signs suggestive of GCA. Ultrasound (US) examination of four vessel territories (i.e. temporal, carotid, subclavian and axillary arteries) was performed bilaterally. Cohort B included all consecutive patients with the diagnosis of GCA evaluated on the fast-track clinic of one of the hospitals (HULP). The halo sign was considered as positive US finding for GCA3. In addition, intima-media thickness of arteries was measured, with a cut-off ≥0.34 mm for temporal arteries (TA) frontal and parietal, 0.42mm for common TA, and ≥1 mm for common carotid, axillary and subclavian arteries for positive result. The clinical characteristics of PMR patients were recorded and the frequency of subclinical GCA determined.ResultsCohort A included 41 PMR patients with subclinical GCA. Cohort B was formed by 97 GCA. The characteristics of the patients are shown in the Table 1. Figure 1 shows the different subtypes of vessel involvement in patients with PMR and subclinical GCA and in patients of the fast-track clinic with the diagnosis of GCA in a single hospital.Figure 1.Subtypes of vessel affectation in Subclinical GCA in PMR and in classical GCATable 1.Clinical characteristics of patients of Cohort A (Subclinical GCA in PMR n = 41/216) and B (GCA in the fast-track clinic n = 97)Cohort A (n = 41)Cohort B (n = 97)Sex female (%)17 (41.5%)53 (54.6%)Age (years) mean ± SD74±6.779 ± 12CRP mg/L49.6±49.146 ± 81.6Polymyalgia rheumatica41 (100%)47 (48.5%)Constitutional symptoms19 (35.18%)35 (36.1%)Subclinical PMR has a predilection for affectation of large vessels, followed by isolated cranial pattern (ie. Isolated temporal artery involvement) and by the mixed (cranial and extra-cranial) form. On the contrary, in classical GCA an isolated cranial involvement represents the more common pattern, followed by the mixed and finally isolated large vessel involvement.ConclusionSubclinical GCA in PMR shows a principal isolated extra-cranial involvement and with clearly different pattern than classical GCA.AcknowledgementsTo the GCA/PMR study groupDisclosure of InterestsNone declared

BackgroundTocilizumab (TCZ) has shown efficacy in large-vessel vasculitis, including Giant Cell Arteritis (GCA) (1-3). Clinical trials with TCZ in GCA was performed with intravenous (iv) TCZ in a phase 2 trial (3), and with subcutaneous (sc) TCZ in the phase 3 GiACTA (4). However, in GCA there are no studies comparing IV vs SC TCZ.ObjectivesTo compare the efficacy of TCZ in GCA patients according to the route of administration IV-TCZ vs SC-TCZ.MethodsMulticentre study of 471 patients diagnosed with GCA and treated with TCZ. They were divided into 2 groups according to the route of administration: a) IV, and b) SC. GCA was diagnosed by: a) ACR criteria, and/or b) temporal artery biopsy, and/or c) imaging techniques. Sustained remission was established according to EULAR definitions (5).ResultsWe studied 471 patients (mean age, 74±9 years) treated with TCZ, 238 with IV-TCZ and 233 with SC-TCZ (Table 1). The time between diagnosis of GCA and TCZ onset was shorter in the SC TCZ group. Regarding acute phase reactants at the beginning of TCZ, no differences were found between both groups. There were no significant differences in sustained remission or in glucocorticoid-sparing effect of TCZ (Figure 1). Patients on IV TCZ treatment suffered more relevant adverse effects during follow-up.Table 1.Main characteristics of GCA patients treated with intravenous and subcutaneous tocilizumabIV TCZ (n= 238)SC TCZ (n=233)PBaseline characteristics at TCZ onsetAge(years), mean±SD73.3±8.773.7±9.30.63Sex, female/male (% female)175/63 (73)167/66 (72)0.65Time from GCA diagnosis to TCZ onset (months), median [IQR]8 [3-23.5]5 [2-15]0.016ESR, mm 1st hour, median [IQR]30.5 [12.5-53]28 [10-56.5]0.66CRP, mg/dL, median [IQR]1.4 [0.5-2.8]1.4 [0.4-4]0.92Prednisone dose, mg/day, median [IQR]20 [10-40]20 [10-36.2]0.69Safety after TCZ onsetFollow-up, (months), median [IQR]27 [16-44]14 [6-26.7]Relevant adverse events, n (%)80 (34)46 (19)Relevant adverse events per 100 patients-year12.715.2NSSerious infections, n (%)44 (18)21 (9)0.44Serious infections per 100 patients-year6.77.2NSMACEs, n (%)/1 (0.4)0 (0)-MACEs per 100 patients-year0.10NSMalignancies, n (%)4 (1.7)1 (0.4)0.20Malignancies per 100 patients-year0.60.3NSAbbreviations: CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; GCA: giant cell arteritis; IQR: interquartile range; IV: intravenous; MACEs: major adverse cardiovascular events; NS: non significant; SC: subcutaneous; SD: standard deviationConclusionIn GCA, TCZ seems equally effective and safe regardless of the route of administration IV or SC.References[1]Calderón-Goercke M, et al. Semin Arthritis Rheum. 2019; 49: 126-135. PMID: 30655091[2]Prieto-Peña D, et al. Ther Adv Musculoskelet Dis. 2021; 13: 1759720X211020917. PMID: 34211589[3]Villiger PM, et al. Lancet. 2016; 387:1921-1927. PMID: 26952547[4]Stone JH, et al. N Engl J Med. 2017; 377:317-328. PMID: 28745999Hellmich B, et al. Ann Rheum Dis. 2020; 79: 19-30. PMID: 31270110Disclosure of InterestsNone declared

BackgroundPolymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are closely related diseases. PMR occurs in approximately 50 % of patients with GCA1; however the prevalence of subclinical GCA in PMR has not yet been widely studied.ObjectivesThe aim of our multicenter, prospective study was to determine the prevalence of subclinical GCA in newly diagnosed PMR, using vascular ultrasound (US) as a diagnostic tool.MethodsEight European centers participated in the study. The studied cohort represented consecutive newly diagnosed patients with PMR who fulfilled 2012 EULAR/ACR Provisional Classification Criteria for Polymyalgia Rheumatica2 without symptoms or signs suggestive for GCA. All patients underwent ultrasound (US) of both hips and shoulders, as well as of four bilateral arterial territories (i.e. temporal, common carotid, subclavian and axillary arteries). Patients with positive halo signs were considered to have subclinical GCA 3. An intima-media thickness ≥0.34 mm for frontal and parietal TA, 0.42mm for common TA, and ≥1 mm for common carotid, axillary and subclavian arteries for positive result. Clinical demographic and laboratory characteristics of the PMR pure group were compared with the PMR/GCA patient group.ResultsA total of 258 patients were included, 137 (53.1%) females with a mean age of 73±8.4 years. Table 1 shows the main differences in PMR patients with and without subclinical GCA. The only statistical significant difference between the two groups was the higher prevalence of morning stiffness > 40 minutes in the pure PMR group (pThe different subtypes of vessel involvement were available in 216 cases. Data compatible with the diagnosis of GCA was found in 41 cases (19%): 10 (24.3%) had only temporal artery involvement (“cranial” GCA), 27 (65.8%) had an extra-cranial artery involvement and 4 (9.8%) a mixed form with both cranial and extra-cranial artery involvement (Figure 1).Table 1.Clinical and demographic characteristicsFigure 1.Subtypes of subclinical GCA in PMR in 216 patients with cranial and extra-cranial examinationConclusionOne fifth of PMR patients without symptoms or signs of GCA have ultrasound findings consistent with the diagnosis of GCA. Subclinical GCA in PMR shows a predilection for extra-cranial artery involvement.References[1]Buttgereit F et al. JAMA. 2016;315:2442-58.[2]Dasgupta B et al. Arthritis & Rheumatism. 2012; 64:943–954.[3]De Miguel E et al. Rheumatology 2018; 57:318-321.AcknowledgementsTo the GCA/PMR study groupDisclosure of InterestsNone declared

BackgroundVisual involvement is the most feared complication of Giant Cell Arteritis (GCA) (1-5). Permanent visual loss (PVL) may be preceded by transient visual loss. Once blindness is established, the prognosis is poor. Most of the series of predictive factors of visual involvement in GCA are old and with a small number of patients.ObjectivesTo assess the predictive factors of visual involvement and PVL in GCA.MethodsMulticenter observational study of 471 patients with GCA. The diagnosis of GCA was performed between 2016 and 2021 according to: a) ACR criteria, and/or b) temporal artery biopsy, and/or c) imaging techniques.From the 471 patients, we selected patients who developed a) visual involvement at any time during GCA and b) PVL. PVL was defined as partial or complete visual loss of >24 hours. Predictive factors were identified by multivariate analysis.ResultsVisual involvement was observed in 122 cases and PVL in 60 (Table 1). The ischemic and systemic manifestations set of variables associated with visual involvement were headache, and jaw claudication, whereas large-vessel involvement was a protective variable (Figure 1). The area under the curve (AUC) for the model was 0.72 (95%CI 0.67-0.77; pFigure 1.Forest plot of multivariate analysis.Table 1.Main features of the patientsOverall (n= 471)GCA without visual involvement (n=349)GCA with visual involvement (n= 122)GCA with PVL (n=60)P visual vs non visual involvementP PVL vs non visual involvementAge at diagnosis of GCA (mean±SD)72±971±975±875±90.0010.001Female/Male (% of female)342/129 (73)265/84 (76)77/45 (63)41/19 (68)0.0060.21Positive TAB, n (%)201 (43)146 (42)55 (45)33 (55)0.530.34Cardiovascular risk factorsHigh blood pressure, n (%)272 (58)189 (54)83 (68)40 (67)0.0130.058Dyslipidemia, n (%)241 (51)175 (50)66 (54)32 (53)0.610.63Diabetes, n (%)81 (17)50 (14)31 (25)16 (27)0.0070.016Previous or current smoking history, n (%)47 (10)31 (9)16 (13)8 (13)0.210.27CHADS2 score, median [IQR]1 [1-2]1 [0-2]2 [1-2]2 [1-2]0.0010.004Ischemic manifestationsHeadache, n (%)259 (55)167 (48)92 (75)42 (70)0.0000.002Jaw claudication, n (%)112 (24)63 (18)49 (40)26 (43)0.0000.000Systemic manifestationsFever, n (%)57 (12)47 (13)10 (8)4 (7)0.120.20Constitutional syndrome, n (%)175 (37)132 (38)43 (35)20 (33)0.550.47PmR, n (%)284 (60)218 (62)66 (54)29 (48)0.0940.022Large-vessel involvement, n (%)254 (54)211 (60)43 (35)20 (33)0.0000.000ESR, mm/1st hour, median [IQR]32 [12-57]30 [11-54]34 [15-67]42 [12-67]0.220.28CRP (mg/dL), median [IQR]1.5 [0.5-3.4]1.4 [0.5-3.0]1.5 [0.4-4.7]1.5 [0.4-3.6]0.0420.30In the same line, the set of variables associated with PVL were headache, and jaw claudication. By contrast, polymyalgia rheumatica (PmR), and large-vessel involvement were protective factors (Figure 1). The AUC for this model was 0.77 (95%CI 0.71-0.83; pConclusionHeadache, and jaw claudication seem to be associated with visual involvement in GCA, while large vessel involvement seems to be a protective factor. PmR also appears to be a protective factor for the development of PVL.References[1]Calderón-Goercke M, et al. Semin Arthritis Rheum. 2019; 49: 126-135. PMID: 30655091[2]Baalbaki H, et al. Clin Rheumatol. 2021; 40: 3207-3217. PMID: 33580374[3]González-Gay MA, et al. Arthritis Rheum. 1998; 41: 1497-1504. PMID: 9704651[4]Prieto-Peña D, et al. Semin Arthritis Rheum. 2019; 48: 720-727. PMID: 29903537[5]Martínez-Rodríguez I, et al. Semin Arthritis Rheum. 2018; 47: 530-537. PMID: 28967430AcknowledgementsTocilizumab in Giant Cell Arteritis Spanish Collaborative Group.Disclosure of InterestsLara Sanchez-Bilbao: None declared, Javier Loricera Speakers bureau: Roche, Novartis, UCB Pharma, Celgene, and Grünenthal, Clara Moriano: None declared, Santos Castañeda Speakers bureau: UAM-Roche, EPID- Future chair, Department of Medicine, Universidad Autónoma de Madrid, Madrid, Spain., Iván Ferraz-Amaro: None declared, J. Narváez: None declared, Vicente Aldasoro: None declared, Olga Maiz: None declared, Rafael Melero: None declared, Ignacio Villa-Blanco: None declared, Paloma Vela-Casasempere: None declared, Susana Romero-Yuste: None declared, Jose Luis Callejas-Rubio: None declared, Eugenio de Miguel: None declared, E. Galíndez-Agirregoikoa: None declared, Francisca Sivera: None declared, Carlos Fernández-López: None declared, Carles Galisteo: None declared, Julio Sanchez-Martin: None declared, Monica Calderón-Goercke: None declared, J. Luis Hernández: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, and MSD., Grant/research support from: AbbVie, MSD, Jansen, and Roche,, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD., Grant/research support from: Abbvie, MSD, and Roche

BackgroundThe EULAR recommendations for the use of imaging in large vessel vasculitis establish that an imaging test supported by clinical pre-test probability (PTP) is sufficient for the diagnosis of giant cell arteritis (GCA)1.ObjectivesTo determine the validity of the EULAR recommendations on the use of Colour doppler ultrasound (CDUS) in GCA after calculating the PTP based on the Southend pre-test probability score (SPTPS).MethodsWe collected data of all patients referred to our fast-track clinic between 2016 and 2020. The SPTPS was calculated and classified as low (LR), intermediate (IR) and high risk (HR) according to the values obtained by its authors, 12, respectively2. All patients underwent a CDUS of the temporal arteries with their common, parietal and frontal branches, and the most also axillary (86.5%), subclavian and carotid arteries. Other diagnostic tests were performed when deemed necessary by the responsible physician. TAB was performed in 34 patients (11.4%), PET-CT in 48 (16.2%) and other imaging tests such as AngioMRI or AngioCT in 8 (2.7%). The gold standard diagnosis was made according to the physician’s criteria after at least nine months of follow-up.ResultsOf the 297 referred patients, 97 (32.7%) were diagnosed with GCA. The SPTPS area under the ROC curve was 0.787. The LR category included 105 patients (35.4%), of which 10 (9.5%) had GCA. The IR category included 125 patients (42.1%), 40 with GCA (32%) and 85 without (68%). The HR category included 67 patients (22.5%), 47 with GCA (70.1%). In 4 of the 97 patients with GCA, the CDUS was negative and the diagnosis was confirmed with PET-CT. On the other hand, 6 of the 200 included patients without GCA (3%) had a false positive result of CDUS.There were 93 patients classified as LR with negative CDUS, and 1 of them has a final clinical diagnosis of GCA. Of the 46 patients classified as HR with positive CDUS, 1 was a false positive diagnosis of GCA. And, within the IR group, of the 84 patients with negative CDUS one had a final GCA diagnosis and of those with positive CDUS 2 were not GCA (Figure 1). Therefore, the combined use of SPTPS + CDUS only miscassified 5/297 cases (Figure 1.Flow-chart of the results of the diagnostic performance of SPTPS + CDUS.ConclusionCombining the results of a pre-test probability score, such as SPTPS, and the CDUS allows for an accurate diagnosis of GCA, as established by the EULAR group, with less than 2% misclassification of diagnosis. Even a negative CDUS in patients with IR shows a strong association with a negative diagnosis.References[1]Dejaco C, Ramiro S, Duftner C, et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis. 2018;77(5):636-643.[2]Sebastian A, Tomelleri A, Kayani A, Prieto-Pena D, Ranasinghe C, Dasgupta B. Probability-based algorithm using ultrasound and additional tests for suspected GCA in a fast-track clinic. RMD Open. 2020;6(3).Disclosure of InterestsNone declared

BackgroundTocilizumab (TCZ) has shown to be useful in the treatment of large-vessel vasculitis, including giant cell arteritis (GCA) (1-4). There is general agreement on the initial and the standard maintenance dose of TCZ. However, information on duration and optimization of TCZ in GCA is really scarce.ObjectivesOur aim was to assess the effectiveness and safety of TCZ therapy optimization in an unselected wide series of GCA in real-world clinical practice.MethodsMulticenter study on 471 patients with GCA who received TCZ therapy. Once complete remission was reached (n=231) TCZ was optimized in 125 patients. We compared patients in whom TCZ was optimized (TCZOPT group) or not (TCZNON-OPT group). Complete remission was defined as normalization of clinical and analytical (CRP and ESR) data. Optimization was done by decreasing the dose and/or prolonging the TCZ dosing interval progressively. We performed a comparison in effectiveness and safety parameters between optimized and non-optimized patients.ResultsWe evaluated 231 GCA patients treated with TCZ with complete remission. No demographic or laboratory data differences was observed at TCZ onset between both groups (Table 1). The mean prednisone dose was higher in the TCZNON-OPT group at TCZ onset. The first TCZ optimization was performed after a median [25-75th] follow-up of 12 [6-17] months.Table 1.Main general features at TCZ onset of 231 GCA patients with prolonged remission.OPTIMIZED-TCZ GROUP (n=125)NON-OPTIMIZED TCZ GROUP (n=106)pGENERAL FEATURES Age, years, mean± SD72.7±8.674±8.70.197 Sex, female/male n (% female)91/34 (72.8)74/32 (69.8)0.616 Time from GCA diagnosis to TCZ onset (months), median [IQR]8 [2-21.5]5 [2-21]0.384SYSTEMIC MANIFESTATIONS Fever, n (%)14 (11.2)15 (14.2)0.500 Constitutional syndrome, n (%)54 (43.2)39 (36.8)0.322 PMR, n (%)75 (60)69 (65.1)0.426ISCHEMIC MANIFESTATIONS Visual involvement, n (%)14 (11.2)16 (15.1)0.380 Headache, n (%)66 (52.8)62 (58.5)0.386 Jaw claudication, n (%)24 (19.2)25 (23.6)0.417AORTITIS (large-vessel involvement), n (%)65 (52)42 (39.6)0.060ANALYTICAL FINDINGS ESR, mm/1st hour, mean (SD)39.1±29.337.5±33.50.334 CRP, mg/dL mean (SD)2.6± 3.42.7± 40.305 Hemoglobin, g/dL, mean (SD)13.5±9.612.9±1.50.153GLUCOCORTICOIDS Prednisone dose, mg/d mean (SD)20.3±16.427±17.80.001Abbreviations: CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; GCA: giant cell arteritis; IQR: interquartile range; IV: intravenous; PMR: polymyalgia rheumatica; SC: subcutaneous; SD: standard deviation; TCZ: tocilizumab.The median prednisone dose at first TCZ optimization was 2.5 [0-5] mg/day. At the end of follow-up prolonged remission was observed in 78.2% of TCZOPT group compared with 66.7% in the TCZNON-OPT group (p= 0.001) (Figure 1). Seven (5.6%) of the 125 optimized cases relapsed. Serious adverse events were similar in both groups, while serious infections were more frequent in the TCZNON-OPT group (p=0.009).ConclusionOnce complete remission is reached in GCA patients under TCZ treatment, optimization of biologic may be performed. Based on our experience it could be performed by reducing the dose or by prolonging dosing interval of TCZ. It seems to be an effective and safe practice.References[1]Calderón-Goercke M, et al. Semin Arthritis Rheum. 2019; 49: 126-135. PMID: 30655091[2]Loricera J, et al. Clin Exp Rheumatol. 2016; 34: S44-53. PMID: 27050507[3]Prieto-Peña D, et al. Ther Adv Musculoskelet Dis. 2021; 13: 1759720X211020917. PMID: 34211589[4]Loricera J, et al. Int Immunopharmacol. 2015; 27: 213-9. PMID: 25828585Disclosure of InterestsCarmen Álvarez-Reguera: None declared, Monica Calderón-Goercke: None declared, J. Loricera: None declared, Clara Moriano: None declared, Santos Castañeda: None declared, J. Narváez: None declared, Vicente Aldasoro: None declared, Olga Maiz: None declared, Rafael Melero: None declared, Ignacio Villa-Blanco: None declared, Paloma Vela-Casasempere: None declared, Susana Romero-Yuste: None declared, Jose Luis Callejas-Rubio: None declared, Eugenio de Miguel: None declared, E. Galíndez-Agirregoikoa: None declared, Francisca Sivera: None declared, Carlos Fernández-López: None declared, Carles Galisteo: None declared, Iván Ferraz-Amaro: None declared, Julio Sanchez-Martin: None declared, Lara Sanchez-Bilbao: None declared, Jose Luis Hernández Hernández: None declared, Miguel Á. González-Gay Consultant of: Abbvie, Pfizer, Roche, Sanofi and MSD., Grant/research support from: Abbvie, MSD, Jansen and Roche., Ricardo Blanco Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD, Grant/research support from: Abbvie, MSD and Roche.

BackgroundGiant cell arteritis GCA is the most frequent vasculitis over the age of 50. Nowadays, it is known that there are several subtypes of GCA depending on the vessels that are involved: cranial, extracranial and mixed. However, the clinical manifestations that differentiate these three subtypes have not been extensively examined until now. In the future, it is likely that the differential characteristics in the expression of the disease will be relevant in the prognosis and the follow up of these patients.ObjectivesThe objective of the study is to investigate the clinical differences associated with these different patterns of GCA involvement.MethodsThis is a retrospective study of new consecutive patients diagnosed with GCA in our hospital for three years. All patients underwent color Doppler ultrasound of both cranial (superficial temporal arteries in the common superficial temporal artery and their frontal and parietal branches) and extracranial arteries (axillary, subclavian and carotid arteries) were explored. The ultrasound diagnosis was made according to the OMERACT definitions of the halo sign and a cut-off the intima media thickness of ≥0.34 mm for the branches of the temporal arteries ≥0.42 in the common superficial temporal artery and ≥ 1 mm for the axillary, subclavian, and carotid arteries was established. The clinical records of the patients were reviewed and their demographic, clinical and laboratory data were compared between the different patterns of ultrasound involvement of GCA. A p< 0.05 was established as the limit of statistical significance. The EULAR recommendations of 20191 were used to establish the definitions of remission and relapse. The statistical analysis was performed using SPSS version 25.ResultsA total of 74 patients were included, 44(58.7%) women with a mean age of 78.6±8.6 years. Regarding the GCA subtypes, 18 (24.3%) patients had exclusive involvement of cranial giant cell arteritis CGCA, 12 (16.2%) patients had isolated involvement of extracranial giant cell arteritis LVGCA and 44 (59.5%) patients had mixed forms with cranial and extracranial MGCA. The characteristics of the population and of the GCA subtypes are shown in Table 1.Table 1.Clinical characteristics and GCA subtypes.Clinical characteristicsTotal GCA = 74CGCA = 18LVGCA = 12MGCA = 44CGCA vs. MGCA pCGCA vs LVGCA pLVGCA vs MGCA PFemale sex, n (%)44 (59.4)10(55.5)6 (50)27 (61.3)0.6720.7650.478Age, mean ± S.D.years78.6 ± 8.679.0 ± 8.173.2 ± 9.480.7 ± 7.90.5050.0310.077ESR, (mm/h) mean S.D.57.1 ± 35.566.1 ± 39.239.6 ± 24.556.6 ± 34.10.3910.0210.115CRP (mg/dL) mean± S.D.56.4 ± 57.150.1 ± 45.652.3 ± 52.560.7 ± 63.70.1790.7580.417Constitutional symptoms, n (%)59 (78.7)12 (66.6)12 (100)35 (79.5)0.2820.0250.087Ischemic symptoms, n (%)66 (82.66)15 (83.3)5 (41.6)35 (79.5)0.7320.0180.010Remission for 6 months, n (%)25 (33.3)7 (38.8)5 (41.6)13 (29.5)0.8470.8790.425Glucocorticoid free remission, n (%)8 (10.7)1 (5.5)2 (16.6)5 (11.3)0.4750.3200.622Major relapse, n (%)4 (5.3)0 (0)1 (8.3)3 (6.8)0.4790.2130.857Minor relapse, n (%)12 (16)2(11.1)3 (25)8 (18.1)0.4920.3170.598GCA: giant cell arteritis; CGCA: Cranial giant cell arteritis; LVGCA: Large vessel giant cell arteritis; MGCA: Mixed giant cell arteritis; SD: standard deviation; p: value.The analysis of the results showed that patients with LVGCA are younger, have less ischemic symptoms and have lower ESR than patients with CGCA pConclusionThere are significant clinical phenotypic differences in the presentation of the different subtypes of vascular involvement in GCA.References[1]Hellmich B et al. Ann Rheum Dis. 2020 Jan;79(1):19-30.Disclosure of InterestsNone declared

The performance of the radon (222Rn)-deficit technique has been evaluated at a site in which a complex DNAPL mixture (mostly hexachlorocyclohexanes and chlorobenzenes) has contaminated all four layers (from top to bottom: anthropic backfill, silt, gravel and marl) of the soil profile. Soil gas samples were collected at two depths (0.8 m and 1.7 m) in seven field campaigns and a total of 186 222Rn measurements were performed with a pulse ionization detector. A statistical assessment of the influence of field parameters on the results revealed that sampling depth and atmospheric pressure did not significantly affect the measurements, while the location of the sampling point and ground-level atmospheric temperature did. In order to remove the bias introduced by varying field temperatures and hence to be able to jointly interpret 222Rn measurements from different campaigns, 222Rn concentrations were rescaled by dividing each individual datum by the mean 222Rn concentration of its corresponding field campaign. Rescaled 222Rn maps showed a high spatial correlation between 222Rn minima and maximum contaminant concentrations in the top two layers of the soil profile, successfully delineating the surface trace of DNAPL accumulation in the anthropic backfill and silt layers. However, no correlation could be established between 222Rn concentrations in superficial soil gas and contaminant concentration in the deeper two layers of the soil profile. These results indicate that the 222Rn-deficit technique is unable to describe the vertical variation of contamination processes with depth but can be an effective tool for the preliminary characterization of sites in which the distance between the inlet point of the sampling probe and the contaminant accumulation falls within the effective diffusion length of 222Rn in the affected soil profile.

Patient satisfaction has become one of the most important outcome measures of quality of care. This study aimed to present the translation, cultural adaptation and validation of a Spanish version of the Patient Satisfaction Questionnaire (PSQ-18) in a sample of Spanish dermatology patients.Cross-cultural linguistic adaptation and translation-backtranslation processes were performed following accepted international guidelines. The psychometric properties, reliability and construct validity were evaluated with Cronbach's alpha and confirmatory factorial analysis respectively. The intraclass correlation coefficient was calculated in a test-retest study, which was conducted on randomly selected participants twice with a 14-21 days interval.240 participants completed the cross-culturally adapted Spanish questionnaire agreed by the researchers. Internal consistency was high (Cronbach's alpha coefficient of 0.834) and confirmatory factorial analysis showed a good model fitting to the model proposed in the original version of the scale. The intraclass correlation coefficients for all the items on the questionnaire were higher than 0.8. CONCLUSIóN: PSQ-18 proved to be a valid and reliable instrument, with psychometric properties suitable for the assessment of satisfaction among dermatology patients.

The radon-deficit technique is a powerful tool to detect and delineate sub-surface accumulations of organic contaminants. Field measurements of 222Rn in soil air, however, are affected by several confounding factors that can lead to the misinterpretation of results. Among the most influential are: vertical and lateral changes of lithology, fluctuating contaminant saturations with depth, varying water saturation ratios along the soil profile and atmospheric (and, therefore, soil) thermal oscillations. To evaluate and minimize the effect of these confounding factors on the interpretation of the results of the Rn deficit technique, a Matlab® based multi-layer model of 222Rn production-partition-diffusion in unsaturated porous media (1D_RnDPM: One-Dimensional 222Rn Diffusion and Partition Model) has been developed and is freely available as Supplementary Material in this work. A laboratory protocol has also been proposed to obtain site-specific input parameters for the model, i.e., 222Rn equilibrium concentration (as determined by the accumulation chamber method), soil bulk density and soil solid-phase density. The model predictions have been contrasted with field information obtained from successive sampling campaigns in which 222Rn in soil air was measured at a site where the vadose zone, consisting of an anthropogenic backfill underlain by a silt layer, is affected by a complex mixture of benzene, phenol, (poly) chlorobenzenes, (poly) chlorophenols and hexachlorocyclohexane isomers, among other compounds. The model has successfully predicted the vertical profile of 222Rn concentrations in soil air, including the effect of the oscillations of the water table and of ground-level temperature. The results also underline that 222Rn measurements in subsoil air are representative only of local conditions around the sampling point, an expected result given that 222Rn maximum effective diffusion length is very limited. As a consequence, the influence of a highly fluctuating water table at the site goes undetected at the sampling depths used in the field campaigns. Main findings The combination of a numerical model and a laboratory protocol allows to predict the activity of 222Rn along the soil profile and to assess the influence of site-specific confounding factors.

Millions of people use rail subway public transport around the world, despite the relatively high particulate matter (PM) concentrations in these underground environments, requiring the identification and quantification of the aerosol source contributions to improve the air quality. An extensive aerosol monitoring campaign was carried out in eleven subway stations in the Barcelona metro system, belonging to seven subway lines. PM2.5 samples were collected during the metro operating hours and chemically analysed to determine major and trace elements, inorganic ions, and total carbon. The chemical compositions of subway components such as brake pads, rail tracks and pantographs were also determined. The mean PM2.5 concentrations varied widely among stations, ranging from 26 µg m−3 to 86 µg m−3. Subway PM2.5 was mainly constituted by Fe2O3 (30–66%), followed by carbonaceous matter (18–37%) for the old stations, while for new stations equipped with Platform Screen Doors (PSD) these percentages go down to 21–44% and 15–30%, respectively. Both the absolute concentrations and the relative abundance of key species differed for each subway station, although with common patterns within a given subway line. This is a result of the different emission chemical profiles in different subway lines (using diverse types of brakes and/or pantographs). The co-emission of different sources poses a problem for their separation by receptor models. Nevertheless, receptor modelling (Positive Matrix Factorization) was applied resulting in ten sources, five of them subway-specific: RailWheel, RailWheel+Brake, Brake_A, Brake_B, Pb. The sum of their contributions accounted for 43–91% of bulk PM2.5 for the old stations and 21–52% for the stations with PSD. The decrease of the activity during the weekends resulted in a decrease (up to 56%) in the subway-specific sources contribution to the –already lower– bulk PM2.5 concentrations compared to weekdays. The health-related elements are mainly apportioned (> 60%) by subway sources. © 2018 The Authors, This work was supported by the European IMPROVE LIFE+ project (LIFE13 ENV/ES/000263 ), the Spanish Ministry of Economy and Competitiveness with FEDER funds (METRO CGL2012–33066 ), the EU Seventh Framework Programme (FP7/2007–2013) under grant agreement n° 315760 HEXACOMM, and the Generalitat de Catalunya (AGAUR 2017 SGR41). M.C. Minguillón acknowledges the Ramón y Cajal fellowship awarded by the Spanish Ministry of Economy, Industry and Competitiveness . Appendix A

Persistence and bioavailability of heavy metals in soils adjacent to ancient Cu mines continues to be a possible threat to human health. However, there have been very few studies to determine this risk. Asturias (Northwest of Spain) is a Cu metallogenic province with abundant epithermal-type deposits, whose paragenetic sequences also include As, Co, Ni, Sb and Hg minerals. Several Cu mines have been worked in this region since prehistoric times and the six most significant ones are studied in this work to provide new insights into the potential for both contemporary and past contamination due to Cu mining to impact human health. The main characteristics of each deposit were defined by means of optical and scanning-electron microscopy, X-ray diffraction and Electron Probe Micro Analysis. These characteristics were used to better interpret the environmental results, obtained from samples of mining wastes, soils and waters, which were analyzed by means of X-ray fluorescence and ICP-MS. Many of these mines are almost forgotten, but their negative effects will endure over time, since they were abandoned long before the introduction of environmental regulations to control metal release. An inheritance of derelict mine facilities and spoil heaps still remains in the sites of this district. The spoil heaps are the main pollution sources and concentrations of up to 2.1% Cu and 0.4% As, among others, were found in the surrounding soils. The potential adverse health effects of the exposure to these elements have been assessed, finding significant risks for potential receptors, such as farmers or local residents.

The present work studies the efficiency of alkaline activated persulfate (PS) to remediate an aged diesel fuel contaminated soil from a train maintenance facility. The Total Petroleum Hydrocarbon (TPH) concentration in soil was approximately 5000mgkg-1 with a ratio of aliphatic:aromatic compounds of 70:30. Aromatic compounds were mainly naphtalenes and phenanthrenes. The experiments were performed in batch mode where different initial concentrations of persulfate (105mM, 210mM and 420mM) and activator:persulfate ratios (2 and 4) were evaluated, with NaOH used as activator. Runs were carried out during 56days. Complete TPH conversion was obtained with the highest concentration of PS and activator, whereas in the other runs the elimination of fuel ranged between 60 and 77%. Besides, the abatement of napthalenes and phenantrenes was faster than aliphatic reduction (i. e. after 4days of treatment, the conversions of the aromatic compounds were around 0.8 meanwhile the aliphatic abatements were 0.55) and no aromatic oxidation intermediates from naphtalenes or phenantrenes were detected. These results show that this technology is effective for the remediation of aged diesel in soil with alkaline pH.

A total of 74 samples of soil, sediment, industrial sludge, and surface water were collected in a Mediterranean estuarine system in order to assess the potential ecological impact of elevated concentrations of Co and Mn associated with a Terephthalic (PTA) and Isophthalic (PIPA) acids production plant. Samples were analyzed for elemental composition (37 elements), pH, redox potential, organic carbon, and CaCO3 content, and a group of 16 selected samples were additionally subjected to a Tessier sequential extraction. Co and Mn soil concentrations were significantly higher inside the industrial facility and around its perimeter than in background samples, and maximum dissolved Co and Mn concentrations were found in a creek near the plant's discharge point, reaching values 17,700 and 156 times higher than their respective background concentrations. The ecological risk was evaluated as a function of Co and Mn fractionation and bioavailability which were controlled by the environmental conditions generated by the advance of seawater into the estuarine system during high tide. Co appeared to precipitate near the river mouth due to the pH increase produced by the influence of seawater intrusion, reaching hazardous concentrations in sediments. In terms of their bioavailability and the corresponding risk assessment code, both Co and Mn present sediment concentrations that result in medium to high ecological risk whereas water concentrations of both elements reach values that more than double their corresponding Secondary Acute Values.

An extensive air quality campaign was performed at differently designed station platforms in the Barcelona metro system, aiming to investigate the factors governing airborne particle number (N) concentrations and their size distributions. The study of the daily trends of N concentrations by different size ranges shows that concentrations of N0.3–10 are closely related with the schedule of the metro service. Conversely, the hourly variation of N0.007–10 (mainly composed of ultrafine particles) could be partly governed by the entrance of particles from outdoor emissions through mechanical ventilation. Measurements under different ventilation settings at three metro platforms reveal that the effect on air quality linked to changes in the tunnel ventilation depends on the station design. Night-time maintenance works in tunnels are frequent activities in the metro system; and after intense prolonged works, these can result in higher N concentrations at platforms during the following metro operating hours (by up to 30%), this being especially evident for N1–10. Due to the complex mixture of factors controlling N, together with the differences in trends recorded for particles within different size ranges, developing an air quality strategy at metro systems is a great challenge. When compared to street-level urban particles concentrations, the priority in metro air quality should be dealing with particles coarser than 0.3 μm. In fact, the results suggest that at narrow platforms served by single-track tunnels the current forced tunnel ventilation during operating hours is less efficient in reducing coarse particles compared to fine.

In order to characterize the influence of environmental factors in dust metal loadings inside homes in an urban environment and to evaluate the associated potential health risks, samples of settled indoor dust from 10 apartments in the urban area of Madrid (Spain) were collected with wet wipes. Cd, Cr, Cu, Pb, Zn, Ni, and Mn loads were determined by Atomic Absorption Spectroscopy (AAS) after a HNO3 + H2O2 digestion. The environmental factors evaluated were load distribution between rooms, number of residents, presence of smokers, traffic intensity, apartment elevation, and frequency of house cleaning. Tukey’s range test and stepwise multiple linear regression analysis revealed that metal dust loadings present two prevailing origins: (1) They present higher loadings in the entry hall, which suggest that dust is tracked indoors adhered to footwear and clothing and (2) they arise from tobacco smoking. Significant correlations were also observed between metal loadings and traffic intensity (Cr), number of residents (Cr, Pb, and Cu), number of days between cleaning (Ni), and flat height (Mn). A human health risk assessment considering a mechanistic hand-to-mouth model for dust ingestion and dermal absorption revealed that urban children are not expected to develop adverse health effects from exposure to trace elements in household dust. The contribution of this exposure scenario to the overall received dose should be included when assessing the background exposure of children to trace elements. A more precise assessment should attempt to reduce the significant uncertainty of the risk model output associated with estimates of exposure variables, deposition rates, and metal bioaccessibility.

Most particles in the rail subway environment are sub-micron sized ferruginous flakes and splinters generated mechanically by frictional wear of brake pads, wheels and rails. To better understand the mechanisms of formation and the alteration processes affecting inhalable particles in subways, PM samples (1-2.5 μm and 2.5-10 μm) were collected in the Barcelona Metro and then studied under a scanning electron microscope. Most particles in these samples are hematitic (up to 88%), with relatively minor amounts of mineral matter (up to 9%) and sulphates (up to 5%). Detailed microscopy (using back scattered and TEM-DRX imaging) reveals how many of the metallic particles comprise the metallic Fe nucleus surrounded by hematite (Fe2O3) and a coating of sulphate and chloride salts mixed with mineral matter (including Ca-carbonates, clay minerals and quartz). These observations record the emission of fine to ultrafine FePM by frictional wear at elevated temperatures that promote rapid partial (or complete) oxidation of the native metal. Water condensing on the PM surface during cooling leads to the adsorption of inorganic mineral particles that coat the iron oxide. The distinctively layered polymineralic structure that results from these processes is peculiar to particles generated in the subway environment and very different from PM typically inhaled outdoors.

Background:There are few data on disease activity status and Quality of Life (QoL) in clinical practice in Spain for patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA).Objectives:To assess the disease activity status in standard clinical practice through BASDAIMethods:An observational, non-interventional, cross-sectional, multicenter study. Patients ≥18 years with ≥6 months diagnosis and classified by ASAS and modified New York criteria or CASPAR criteria undergoing treatment ≥3 months. At the cross-sectional visit, the principal variable taken was the percentage of patients under remission and low disease activity according to the national and European recommendations1-3, assessed through BASDAI and ASDAS-CRP in AS or DAPSA and MDA in PsA. The relationship between patients’ QoL and disease activity were assessed using ASAS-HI in AS and PSAID in PsA.Results:313 AS patients were included, 75.7% male, 78.5% HLA-B*27+, with a mean (SD) age of 50.4 (12.0) years, a mean (SD) disease duration of 15.5 (11.6) years and a mean (SD) CRP of 5.1 (8.2) mg/l. 313 PsA patients were included, 54.3% male, 17.95% HLA-B*27+, with a mean (SD) age of 54.1 (12.2) years, a mean (SD) disease duration of 10.5 (9.0) years and a mean (SD) CRP of 4.91 (7.3) mg/l. 29.7% AS patients were on biological and 26.8% were on non-biological therapy vs 17.9% and 40.9% PsA patients, respectively. According to BASDAI, 64.5% AS patients were on LDA and 29.4% PsA patients had inactive disease by ASDAS-CRP, 59.4% of patients had a DAPSAConclusion:Our observations show that most AS and PsA patients have an inactive disease, whereas 36% and 41% of AS and PsA patients, respectively, are inadequately controlled despite therapy in standard clinical practice in Spain, which is associated to a significantly worse QoL.References:[1]Torre Alonso JC et al. Reumatol Clin 2018;14:254-68[2]Smolen JS et al. Ann Rheum Dis 2018;77:3-17[3]Gratacós J et al. Reumatol Clin 2018;14:320-33Table 1.AS and PsA scores according to the current treatment.Valid NMean (SD)95% (CI)ASDisease control(BASDAI) Not under remission(BASDAI1119.3 (3.7)(8.6; 10.0) Under remission(BASDAI≥4)2023.9 (3.4)(3.4; 4.4) Total3135.8 (4.4)(5.3; 6.3)Disease activity(ASDAS-CRP) ASDAS-CRP≥1.32217.1 (4.1)(6.6; 7.7) ASDAS-CRP922.7 (3.4)(2.0; 3.4) Total3135.8 (4.4)(5.3; 6.3)PsA Disease control(DAPSA) Not under remission(DAPSA>14)1274.5 (2.4)(4.1; 4.9) Under remission(DAPSA≤14)1861.9 (1.7)(1.7; 2.2) Total3133.0 (2.4)(2.7; 3.2)Active disease (MDA) Inactive(MDA criteria ≥5)1611.5 (1.4)(1.3; 1.7) Active(does not meet MDA criteria)1524.5 (2.2)(4.2; 4.8) Total3133.0 (2.4)(2.7; 3.2)Acknowledgments:MIDAS groupDisclosure of Interests:José L. Pablos Consultant of: Pfizer, Lilly, Novartis, Roche, Celgene, Sanofi, Gilead, Biogen, Paid instructor for: Bristol, Speakers bureau: Abbvie, Janssen, Pfizer, Lilly, Novartis, Roche, Celgene, Bristol, Sanofi, Cristina Fernández-Carballido Consultant of: Yes, I have received fees for scientific advice (Abbvie, Celgene, Janssen, Lilly and Novartis), Speakers bureau: Yes, I have received fees as a speaker (Abbvie, Celgene, Janssen, Lilly, MSD, Novartis), Xavier Juanola Consultant of: Pfizer, Lilly, Novartis, Roche, Celgene, Sanofi, Gilead, Biogen, Paid instructor for: Bristol, Speakers bureau: Abbvie, Janssen, Pfizer, Lilly, Novartis, Roche, Celgene, Bristol, Sanofi, Jordi Gratacos-Masmitja Grant/research support from: a grant from Pfizzer to study implementation of multidisciplinary units to manage PSA in SPAIN, Consultant of: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Speakers bureau: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Rafael Ariza-Ariza: None declared, Cristina Sanabra Employee of: Yes: employed as a Medical Advisor (Novartis), Pau Terradas Employee of: Yes: employed as a Medical Advisor (Novartis), Carlos Sastré Employee of: YES; I´m Medical Advisor in Novartis Spain

Background BO-112 is a dsRNA (poly I:C) formulated with polyethylenimine, that upon Intratumoral (IT) injection acts by activating TLR3, RIG-1 and MDA-5. This induces immunogenic cell death and potentiate systemic therapy with checkpoint inhibitors in animal models. In patients (pts), single-agent BO-112 IT increases necrosis, apoptosis and expression of pro-immune genes in solid cancers, with a manageable safety. 1 mg was the dose combined with anti-PD-1 in the current clinical trial (NCT02828098). Methods BO-112 was combined with anti PD-1 in 28 pts with solid tumors primarily resistant to anti PD-1 (nivolumab or pembrolizumab). A lesion >1 cm amenable to IT injection was required. 28 pts were treated with 1 mg IT BO-112 qw x 2 or 3 doses before continuing the previous anti PD-1 combined with BO-112, until progression, limiting toxicity or up to 1y. Pre & post BO-112 biopsies from injected lesion were analysed. Response was first assessed by RECIST 1.1 at week 8-12. Results BO-112 related AEs and biological effects at interim analysis are summarized in the table. The combination was well tolerated. No deaths were associated with BO-112. Of 18 evaluable pts for response, at first assessment: 2 have achieved an objective partial response (PR) (1 melanoma and 1 renal carcinoma), with 1 of them continuing treatment; 11 patients had stable disease (SD); 5 patients progressed (PD). Additionally 6 patients progressed prior to the first evaluation, 3 died before efficacy assessments and 1 received palliative radiotherapy and was considered not evaluable. Table . 100P All G3-5 TEAEs (%) G3-4 BO-112 related TEAEs (%) Necrosis (D > 5%) (%)* CD8+ T cell infiltrate (D > 5%) (%)* *evaluable All N = 28 18 (64) 1 (4) 10 (50) 7 (35) Melanoma N = 10 7 (70) 0 5 (56) 4 (44) Non-Small lung cancer N = 13 8 (62) 1 (8) 3 (38) 1 (13) Other N = 5 3 (60) 0 2 (67) 2 (67) Conclusion BO-112 combined with anti PD-1 shows a manageable safety profile, direct antitumor effects and innate and adaptive immune system activation. Efficacy analyses suggest potential to reverse primary resistance to anti-PD1 treatment. Studies in other indications, including combination with radiotherapy, are planned. Clinical trial identification NCT02828098. Legal entity responsible for the study Bioncotech Therapeutics. Funding Bioncotech Therapeutics. Disclosure I. Marquez-Rodas: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bioncotech; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Regeneron; Advisory / Consultancy, Research grant / Funding (institution): Incyte; Non-remunerated activity/ies: Biosequence; Research grant / Funding (institution): Idera. P. Lopez-Casas: Full / Part-time employment: Bioncotech. M. Martin: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Puma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy: Tahio; Advisory / Consultancy: Pharmamar; Advisory / Consultancy: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Daiichi. D. Tersago: Full / Part-time employment: Bioncotech. M. Quintero: Full / Part-time employment, Officer / Board of Directors: Bioncotech. I. Melero: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Alligator; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Merck-Serono; Advisory / Consultancy: Genentech; Advisory / Consultancy: Genmab; Advisory / Consultancy: Incyte; Advisory / Consultancy: Tusk; Advisory / Consultancy: Numab; Advisory / Consultancy: Molecular Partners; Advisory / Consultancy: F Star; Advisory / Consultancy: Bayer; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.