Fine-tuning characterization of patients with interstitial pneumonia and an underlying autoimmune disease in real-world practice: We get closer with Nailfold videocapillaroscopy.

Objectives: To assess performance of interstitial pneumonia (IP) with autoimmune features (IPAF) criteria in clinical practice and describe the utility of additional workup in identifying patients with underlying connective tissue diseases (CTD). Methods: We set a retrospective study of our patients with autoimmune IP, who were allocated to CTD-IP, IPAF or undifferentiated autoimmune IP (uAIP) subgroups according to the updated classification criteria. Presence of the process-related variables comprising IPAF defining domains was scrutinized in all patients, and, when available, the results of nailfold videocapillaroscopy (NVC) were recorded. Results: Thirty nine out of 118 patients, accounting for 71% of former undifferentiated cases, fulfilled IPAF criteria. Arthritis and Raynaud's phenomenon were prevalent in this subgroup. While systemic sclerosis-specific autoantibodies were restricted to CTD-IP patients, anti-tRNA synthetase antibodies were also present in IPAF. In contrast, rheumatoid factor, anti-Ro antibodies and ANA nucleolar patterns could be found in all subgroups. Usual interstitial pneumonia (UIP) / possible UIP were the most frequently observed radiographic patterns Therefore, the presence of thoracic multicompartimental findings as also performance of open lung biopsies were useful in characterizing as IPAF those UIP cases lacking a clinical domain. Interestingly, we could observe NVC abnormalities in 54% of IPAF and 36% of uAIP tested patients, even though many of them did not report Raynaud's phenomenon. Conclusion: Besides application of IPAF criteria, distribution of IPAF defining variables along with NVC exams help identify more homogeneous phenotypic subgroups of autoimmune IP of potential relevance beyond clinical diagnosis.

Functional respiratory impairment and related factors in patients with interstitial pneumonia with autoimmune features (IPAF): Multicenter study from NEREA registry.

BACKGROUND: The objective of the present study is to describe the characteristics of interstitial pneumonia with autoimmune features (IPAF) patients, to assess the incidence rate of functional respiratory impairment over time and to evaluate the influence of therapeutic alternatives on the prognosis of these patients. METHODS: A longitudinal observational multicenter study was performed (NEREA registry). It was carried out by a multidisciplinary team in seven Hospitals of Madrid. Patients were included from IPAF diagnosis. MAIN OUTCOME: poor prognosis as functional respiratory impairment (relative decline in FVC % defined as ≥ 5% every 6 months). Covariates: therapy, sociodemographic, clinical, radiological patterns, laboratory and functional tests. STATISTICS: Survival techniques were used to estimate IR per 100 patients-semester with their 95% confidence interval [CI]. The influence of covariates in prognosis were analyzed through cox multivariate regression models (hazard ratio (HR) and [CI]). RESULTS: 79 IPAF were included, with a mean and a maximum follow-up of 3.17 and 12 years respectively. Along the study, 77.2% received treatment (52 glucocorticoids, 25 mycophenolate, 21 azathioprine, 15 rituximab and 11 antifibrotics). IR was 23.9 [19.9-28.8], and 50% of IPAF developed functional respiratory impairment after 16 months from its diagnosis. Multivariate analysis: usual interstitial pneumonia (UIP) had poorer prognosis compared to non-specific interstitial pneumonia (NSIP) (p = 0.001). In NSIP, positive ANA, increased the risk of poor prognosis. In UIP, glucocorticoids (HR: 0.53 [0.34-0.83]), age (HR: 1.04 [1.01-1.07]), and Ro-antibodies (HR: 0.36 [0.19-0.65]) influenced the prognosis. CONCLUSIONS: IPAF have functional impairment during the first years of disease. Factors predicting deterioration differ between radiographic patterns. Our real-life study suggests the potential benefit of particular therapies in IPAF.

Myo-Spain: Registro de pacientes con miopatía inflamatoria idiopática de España. Metodología / Myo-Spain: Spanish Registry of Patients with Idiopathic Inflammatory Myopathy. Methodology

Objetivos: Describir la metodología del Registro de pacientes con miopatía inflamatoria idiopática (MII) de España (Myo-Spain), así como sus fortalezas y limitaciones. El objetivo principal del proyecto es analizar la evolución y el manejo clínico de una cohorte de pacientes con MII. Material y método: Estudio observacional, longitudinal, ambispectivo y multicéntrico de una cohorte de pacientes con MII atendidos en servicios de reumatología de España. Se incluirán todos los pacientes con diagnóstico de MII en seguimiento habitual por los centros participantes, sin tener en cuenta la edad de inicio del proceso. Los casos incidentes serán todos los pacientes que al inicio del estudio en cada centrosu estén diagnosticados desde hace menos de 12 meses y casos prevalentes desde hace más de 12 meses. Se construirá un registro en el que se incluirán los datos de la visita basal, del año y dos años. Se recogerán variables sociodemográficas, clínicas, analíticas, complicaciones, comorbilidad, asociación con otras enfermedades reumáticas, ingresos hospitalarios, mortalidad y tratamientos. Además, se determinarán índices, escalas y cuestionarios de actividad, afectación muscular, daño, discapacidad y calidad de vida. El periodo de reclutamiento será de 23 meses. El propósito es conseguir una cohorte de 400 pacientes con MII. Conclusion: esEl estudio Myo-Spain constituye la oportunidad para desarrollar una cohorte de pacientes incidentes y prevalentes con MII en España. Myo-Spain permitirá evaluar en detalle, las características clínicas de la enfermedad en diferentes momentos. Se espera que la información exhaustiva recogida en las visitas suponga una amplia fuente de datos para futuros análisis.(AU)

Objectives: To describe the methods of the Spanish Registry of patients with idiopathic inflammatory myopathy (IIM) (Myo-Spain), as well as its strengths and limitations. The main objective of the project is to analyse the evolution and clinical management of a cohort of patients with IIM. Methods: Observational, longitudinal, ambispective and multicentre study of a cohort of patients with IIM seen in rheumatology units in Spain. All patients with a diagnosis of IMM will be included in the regular follow-up of the participating centres, regardless of age on initiation of the process. Incident cases will be all patients who at the beginning of the study have been diagnosed for less than 12 months and prevalent cases for more than 12 months. The registry will include data from the visit at baseline, one year and two years. Socio-demographic, clinical, analytical variables, complications, comorbidities, association with other rheumatic diseases, hospital admissions, mortality and treatments will be collected. In addition, indices, scales and questionnaires of activity, muscle involvement, damage, disability, and quality of life will be determined. The recruitment period will be 23 months. The purpose is to obtain a cohort of 400 patients with IMM. Conclusions: Myo-Spain registry provides the opportunity to develop a cohort of incident and prevalent patients with IMM in Spain. Myo-Spain will be able to assess in detail the clinical characteristics of the disease at different times. The comprehensive information collected during the visits is expected to provide a broad source of data for future analysis.(AU)

Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies.

OBJECTIVES: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. METHODS: We conducted a multicentre, international, retrospective cohort study. RESULTS: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. CONCLUSIONS: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Educación y uso de la ecografía pulmonar en reumatología y neumología en España: encuesta SER-SEPAR / Education and Use of Lung Ultrasound in Rheumatology and Pneumology in Spain: A SER-SEPAR Survey

Introducción: La ecografía pulmonar (ECOPULM) es una herramienta clínica y de investigación con un gran potencial en el diagnóstico y seguimiento de las enfermedades pulmonares intersticiales difusas (EPID) presentes en las enfermedades autoinmunes sistémicas (EAS). La formación apropiada en ECOPULM es esencial para el uso correcto y seguro de esta técnica. Objetivo: Conocer la formación y uso de la ECOPULM entre los reumatólogos y neumólogos españoles. Material y métodos: Se diseñó una encuesta nacional en línea, dirigida a los socios de la Sociedad Española de Reumatología y del Área de EPID de la Sociedad Española de Neumología y Cirugía Torácica. La encuesta constaba de 22 preguntas sobre demografía y actividad profesional, realización y formación en ECOPULM. Resultados: Ciento treinta y cinco socios (56,72% reumatólogos, 41,79% neumólogos) respondieron la encuesta. De ellos, el 56,30% formaban parte de una Unidad EPID en su centro. El 35,82% declararon que realizaban ECOPULM en su práctica clínica pero solo un 14,93% la realizaba en EPID, fundamentalmente con fines diagnósticos. La formación en ECOPULM de los respondedores había sido diversa en formato, contenido y auspiciadores. La gran mayoría (87,79%) consideraron que el modelo óptimo de educación en ECOPULM debería ser estandarizado y estructurado y consistir en una combinación formativa de cursos teórico-prácticos y la realización de un número mínimo de exploraciones ecográficas pulmonares supervisadas, con evaluación de competencia. Conclusiones: La carencia actual de formación estructurada formal en ECOPULM supone una oportunidad para desarrollar programas educacionales de calidad en este campo emergente.(AU)

Introduction: Lung ultrasound (LUS) is a clinical and research tool with great potential in the diagnosis and monitoring of diffuse interstitial lung disease (ILD) present in systemic autoimmune diseases (SAD). Appropriate training in LUS is essential for the correct and safe use of this technique. Objective: To document the current state of LUS education and use among Spanish rheumatologists and pneumologists. Material and Methods: A national online survey was designed for members of the Spanish Society of Rheumatology and the ILD Area of the Spanish Society of Pneumology and Thoracic Surgery. The survey consisted of 22 questions on demographics, professional activity, performance and training in LUS. Results: One hundred and thirty-five (56.72% rheumatologists, 41.79% pneumologists) responded to the survey. Of these, 56.30% were part of an ILD Unit in their centre. LUS in clinical practice was performed by 35.82% but only 14.93% performed it in ILD, mainly for diagnostic purposes. Training in LUS of responders had been diverse in format, content and sponsors. The vast majority (87.79%) considered that the optimal model of education in LUS should be standardized and structured and consist of a combination of theoretical-practical courses and the conduct of a minimum number of supervised LUS examinations, with competency assessment. Conclusions: The current lack of formal structured education in LUS is an opportunity to develop quality educational programmes in this emerging field.(AU)

Education and Use of Lung Ultrasound in Rheumatology and Pneumology in Spain: A SER-SEPAR Survey.

INTRODUCTION: Lung ultrasound (LUS) is a clinical and research tool with great potential in the diagnosis and monitoring of diffuse interstitial lung disease (ILD) present in systemic autoimmune diseases (SAD). Appropriate training in LUS is essential for the correct and safe use of this technique. OBJECTIVE: To document the current state of LUS education and use among Spanish rheumatologists and pneumologists. MATERIAL AND METHODS: A national online survey was designed for members of the Spanish Society of Rheumatology and the ILD Area of the Spanish Society of Pneumology and Thoracic Surgery. The survey consisted of 22 questions on demographics, professional activity, performance and training in LUS. RESULTS: One hundred and thirty-five (56.72% rheumatologists, 41.79% pneumologists) responded to the survey. Of these, 56.30% were part of an ILD Unit in their centre. LUS in clinical practice was performed by 35.82% but only 14.93% performed it in ILD, mainly for diagnostic purposes. Training in LUS of responders had been diverse in format, content and sponsors. The vast majority (87.79%) considered that the optimal model of education in LUS should be standardized and structured and consist of a combination of theoretical-practical courses and the conduct of a minimum number of supervised LUS examinations, with competency assessment. CONCLUSIONS: The current lack of formal structured education in LUS is an opportunity to develop quality educational programmes in this emerging field.

Myo-Spain: Spanish Registry of patients with idiopathic inflammatory myopathy. Methodology.

OBJECTIVES: To describe the methods of the Spanish Registry of patients with idiopathic inflammatory myopathy (IIM) (Myo-Spain), as well as its strengths and limitations. The main objective of the project is to analyse the evolution and clinical management of a cohort of patients with IIM. METHODS: Observational, longitudinal, ambispective and multicentre study of a cohort of patients with IIM seen in rheumatology units in Spain. All patients with a diagnosis of IMM will be included in the regular follow-up of the participating centres, regardless of age on initiation of the process. Incident cases will be all patients who at the beginning of the study have been diagnosed for less than 12 months and prevalent cases for more than 12 months. The registry will include data from the visit at baseline, one year and two years. Socio-demographic, clinical, analytical variables, complications, comorbidities, association with other rheumatic diseases, hospital admissions, mortality and treatments will be collected. In addition, indices, scales and questionnaires of activity, muscle involvement, damage, disability, and quality of life will be determined. The recruitment period will be 23 months. The purpose is to obtain a cohort of 400 patients with IMM. CONCLUSIONS: Myo-Spain registry provides the opportunity to develop a cohort of incident and prevalent patients with IMM in Spain. Myo-Spain will be able to assess in detail the clinical characteristics of the disease at different times. The comprehensive information collected during the visits is expected to provide a broad source of data for future analysis.

Non-infectious Uveitis as a Manifestation of the Immune Reconstitution Inflammatory Syndrome in Patients Infected by HIV.

OBJECTIVE: To describe a retrospective review of HIV patients with noninfectious uveitis. Data collected included: demographics, anatomic classification and phenotypic diagnosis of the uveitis, systemic immune-mediated disorders (IMD), time from HIV diagnosis to uveitis, CD4 count, viral load, treatment and complications of treatment and time of follow-up. RESULTS: Twenty patients (18 males) were included. The time lag between HIV diagnosis and the onset of uveitis was 9 ± 8.5 years. Mean CD4 count was 670 ± 294 cells/ml. Viral load was undetectable in 14 out of 18 cases. In 6 patients IMD was diagnosed prior to or concurring with the uveitis diagnosis. The use of immunosuppressive therapies was necessary in 6 patients (including biologics in 4 cases). The mean follow-up was 42.2 months. CONCLUSIONS: noninfectious uveitis could be the first manifestation of IMD in patients with well-controlled HIV infection. Immunosuppression appeared to be a safe therapeutic option in our cohort of patients.

Role of MUC1 rs4072037 polymorphism and serum KL-6 levels in patients with antisynthetase syndrome.

Mucin 1/Krebs von den Lungen-6 (KL-6) is proposed as a serum biomarker of several interstitial lung diseases (ILDs), including connective tissue disorders associated with ILD. However, it has not been studied in a large cohort of Caucasian antisynthetase syndrome (ASSD) patients. Consequently, we assessed the role of MUC1 rs4072037 and serum KL-6 levels as a potential biomarker of ASSD susceptibility and for the differential diagnosis between patients with ILD associated with ASSD (ASSD-ILD +) and idiopathic pulmonary fibrosis (IPF). 168 ASSD patients (149 ASSD-ILD +), 174 IPF patients and 523 healthy controls were genotyped for MUC1 rs4072037 T > C. Serum KL-6 levels were determined in a subgroup of individuals. A significant increase of MUC1 rs4072037 CC genotype and C allele frequencies was observed in ASSD patients compared to healthy controls. Likewise, MUC1 rs4072037 TC and CC genotypes and C allele frequencies were significantly different between ASSD-ILD+ and IPF patients. Additionally, serum KL-6 levels were significantly higher in ASSD patients compared to healthy controls. Nevertheless, no differences in serum KL-6 levels were found between ASSD-ILD+ and IPF patients. Our results suggest that the presence of MUC1 rs4072037 C allele increases the risk of ASSD and it could be a useful genetic biomarker for the differential diagnosis between ASSD-ILD+ and IPF patients.

Mortality rate in rheumatoid arthritis-related interstitial lung disease: the role of radiographic patterns.

BACKGROUND: To assess mortality rate (MR) and standardized mortality rate (SMR) of rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients and to evaluate the role of radiographic patterns in mortality. METHODS: A longitudinal multicentric study was conducted in RA-ILD patients from 2005 to 2015 and followed-up until October 2018 in Madrid. Patients were included in the Neumologia-Reumatología y Enfermedades Autoinmunes Registry, from diagnosis of ILD. The main outcome was all-cause mortality. The radiographic pattern at baseline [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), or others] was the independent variable. Covariables included sociodemographic and clinical data. Survival techniques were used to estimate MR, expressed per 1000 persons-year with their 95% confidence intervals [CI]. Cox multiple regression model was run to examine the influence of radiographic patterns on survival. SMR [CI] was calculated comparing MR obtained with MR expected in the general population of Madrid by indirect age-gender standardization. RESULTS: 47 patients were included with a follow-up 242 patients-year. There were 16 (34%) deaths, and most frequent causes were acute ILD exacerbation and pneumonia. MR was 64.3 [39.4-104.9], and 50% of the patients died at 8.3 years from ILD diagnosis. After adjusting for confounders, (UIP compared to NSIP was associated with higher mortality risk. The overall SMR was 2.57 [1.4-4.17]. Women of 60-75 years of age were the group with the highest SMR. CONCLUSIONS: RA-ILD is associated with an excess of mortality compared to general population. Our results support that UIP increases the risk of mortality in RA-ILD, regardless other factors.

Myo-Spain: Spanish Registry of Patients with Idiopathic Inflammatory Myopathy. Methodology. / Myo-Spain: Registro de pacientes con miopatía inflamatoria idiopática de España. Metodología.

OBJECTIVES: To describe the methods of the Spanish Registry of patients with idiopathic inflammatory myopathy (IIM) (Myo-Spain), as well as its strengths and limitations. The main objective of the project is to analyse the evolution and clinical management of a cohort of patients with IIM. METHODS: Observational, longitudinal, ambispective and multicentre study of a cohort of patients with IIM seen in rheumatology units in Spain. All patients with a diagnosis of IMM will be included in the regular follow-up of the participating centres, regardless of age on initiation of the process. Incident cases will be all patients who at the beginning of the study have been diagnosed for less than 12 months and prevalent cases for more than 12 months. The registry will include data from the visit at baseline, one year and two years. Socio-demographic, clinical, analytical variables, complications, comorbidities, association with other rheumatic diseases, hospital admissions, mortality and treatments will be collected. In addition, indices, scales and questionnaires of activity, muscle involvement, damage, disability, and quality of life will be determined. The recruitment period will be 23 months. The purpose is to obtain a cohort of 400 patients with IMM. CONCLUSIONS: Myo-Spain registry provides the opportunity to develop a cohort of incident and prevalent patients with IMM in Spain. Myo-Spain will be able to assess in detail the clinical characteristics of the disease at different times. The comprehensive information collected during the visits is expected to provide a broad source of data for future analysis.

First and Second Waves of Coronavirus Disease 2019 in Madrid, Spain: Clinical Characteristics and Hematological Risk Factors Associated With Critical/Fatal Illness.

OBJECTIVES: This study aims to determine similarities and differences in clinical characteristics between the patients from two waves of severe acute respiratory syndrome coronavirus-2 infection at the time of hospital admission, as well as to identify risk biomarkers of coronavirus disease 2019 severity. DESIGN: Retrospective observational study. SETTING: A single tertiary-care center in Madrid. PATIENTS: Coronavirus disease 2019 adult patients admitted to hospital from March 4, 2020, to March 25, 2020 (first infection wave), and during July 18, 2020, and August 20, 2020 (second infection wave). INTERVENTIONS: Treatment with a hospital-approved drug cocktail during hospitalization. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, and laboratory data were compared between the patients with moderate and critical/fatal illness across both infection waves. The median age of patients with critical/fatal coronavirus disease 2019 was 67.5 years (interquartile range, 56.75-78.25 yr; 64.5% male) in the first wave and 59.0 years (interquartile range, 48.25-80.50 yr; 70.8% male) in the second wave. Hypertension and dyslipidemia were major comorbidities in both waves. Body mass index over 25 and presence of bilateral pneumonia were common findings. Univariate logistic regression analyses revealed an association of a number of blood parameters with the subsequent illness progression and severity in both waves. However, some remarkable differences were detected between both waves that prevented an accurate extrapolation of prediction models from the first wave into the second wave. Interleukin-6 and d-dimer concentrations at the time of hospital admission were remarkably higher in patients who developed a critical/fatal condition only during the first wave (p < 0.001), although both parameters significantly increased with disease worsening in follow-up studies from both waves. Multivariate analyses from wave 1 rendered a predictive signature for critical/fatal illness upon hospital admission that comprised six blood biomarkers: neutrophil-to-lymphocyte ratio (≥ 5; odds ratio, 2.684 [95% CI, 1.143-6.308]), C-reactive protein (≥ 15.2 mg/dL; odds ratio, 2.412 [95% CI, 1.006-5.786]), lactate dehydrogenase (≥ 411.96 U/L; odds ratio, 2.875 [95% CI, 1.229-6.726]), interleukin-6 (≥ 78.8 pg/mL; odds ratio, 5.737 [95% CI, 2.432-13.535]), urea (≥ 40 mg/dL; odds ratio, 1.701 [95% CI, 0.737-3.928]), and d-dimer (≥ 713 ng/mL; odds ratio, 1.903 [95% CI, 0.832-4.356]). The predictive accuracy of the signature was 84% and the area under the receiver operating characteristic curve was 0.886. When the signature was validated with data from wave 2, the accuracy was 81% and the area under the receiver operating characteristic curve value was 0.874, albeit most biomarkers lost their independent significance. Follow-up studies reassured the importance of monitoring the biomarkers included in the signature, since dramatic increases in the levels of such biomarkers occurred in critical/fatal patients over disease progression. CONCLUSIONS: Most parameters analyzed behaved similarly in the two waves of coronavirus disease 2019. However, univariate logistic regression conducted in both waves revealed differences in some parameters associated with poor prognosis in wave 1 that were not found in wave 2, which may reflect a different disease stage of patients on arrival to hospital. The six-biomarker predictive signature reported here constitutes a helpful tool to classify patient's prognosis on arrival to hospital.

Education and Use of Lung Ultrasound in Rheumatology and Pneumology in Spain: A SER-SEPAR Survey. / Educación y uso de la ecografía pulmonar en reumatología y neumología en España: encuesta SER-SEPAR.

INTRODUCTION: Lung ultrasound (LUS) is a clinical and research tool with great potential in the diagnosis and monitoring of diffuse interstitial lung disease (ILD) present in systemic autoimmune diseases (SAD). Appropriate training in LUS is essential for the correct and safe use of this technique. OBJECTIVE: To document the current state of LUS education and use among Spanish rheumatologists and pneumologists. MATERIAL AND METHODS: A national online survey was designed for members of the Spanish Society of Rheumatology and the ILD Area of the Spanish Society of Pneumology and Thoracic Surgery. The survey consisted of 22 questions on demographics, professional activity, performance and training in LUS. RESULTS: One hundred and thirty-five (56.72% rheumatologists, 41.79% pneumologists) responded to the survey. Of these, 56.30% were part of an ILD Unit in their centre. LUS in clinical practice was performed by 35.82% but only 14.93% performed it in ILD, mainly for diagnostic purposes. Training in LUS of responders had been diverse in format, content and sponsors. The vast majority (87.79%) considered that the optimal model of education in LUS should be standardized and structured and consist of a combination of theoretical-practical courses and the conduct of a minimum number of supervised LUS examinations, with competency assessment. CONCLUSIONS: The current lack of formal structured education in LUS is an opportunity to develop quality educational programmes in this emerging field.

Compassionate use of tocilizumab in severe SARS-CoV2 pneumonia.

INTRODUCTION: Tocilizumab (TCZ) is an interleukin-6 receptor antagonist, which has been used for the treatment of severe SARS-CoV-2 pneumonia (SSP), which aims to ameliorate the cytokine release syndrome (CRS) induced acute respiratory distress syndrome (ARDS). However, there are no consistent data about who might benefit most from it. METHODS: We administered TCZ on a compassionate-use basis to patients with SSP who were hospitalized (excluding intensive care and intubated cases) and who required oxygen support to have a saturation >93%. The primary endpoint was intubation or death after 24 h of its administration. Patients received at least one dose of 400 mg intravenous TCZ from March 8, 2020 to April 20, 2020. RESULTS: A total of 207 patients were studied and 186 analyzed. The mean age was 65 years and 68% were male patients. A coexisting condition was present in 68% of cases. Prognostic factors of death were older age, higher IL-6, d-dimer and high-sensitivity C-reactive protein (HSCRP), lower total lymphocytes, and severe disease that requires additional oxygen support. The primary endpoint (intubation or death) was significantly worst (37% vs 13%, p < 0·001) in those receiving the drug when the oxygen support was high (FiO2 >0.5%). CONCLUSIONS: TCZ is well tolerated in patients with SSP, but it has a limited effect on the evolution of cases with high oxygen support needs.

Intraocular leucocyte subpopulations analysis by multiparametric flow cytometry in human uveitis.

PURPOSE: The aim of this study was to describe the cellular infiltrate in aqueous and vitreous samples of patients with uveitis analysed by multiparametric flow cytometry. METHODS: This is a retrospective analysis of aqueous and vitreous samples analysed by flow cytometry for diagnostic purposes, in cases of masquerade syndromes and infectious and non-infectious uveitis. Data collected included demographics, anatomical classification of uveitis, phenotypic diagnosis, anterior chamber cells grading, vitreous haze and time of follow-up since presentation to sample obtained. RESULTS: Thirty-one samples (17 aqueous and 14 vitreous fluids) from 31 patients, 18 men, were analysed. The mean age at the time of sample collection was 60.23±17.03 years. The most frequent anatomical classification was panuveitis (14 of 31). T cells accounted for the main cellular component in the majority of the samples (10 of 13 aqueous samples; 7 of 14 in vitreous samples). CD4:CD8 ratios ranged from 0.21 to 16.3 in the case of aqueous samples and from 0.5 to 9.7 in the case of vitreous samples. DISCUSSION: Flow cytometry analysis of aqueous and vitreous samples from patients with uveitis could provide insight into the pathogenesis of human uveitis and help develop accurate animal models which better mimic human disease.

HLA association with the susceptibility to anti-synthetase syndrome.

OBJECTIVE: To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD). METHODS: We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing. RESULTS: A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P=1.56E-09, odds ratio-OR [95% confidence interval-CI]=2.54 [1.84-3.50] and 21.4% versus 5.5%, P=18.95E-18, OR [95% CI]=4.73 [3.18-7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P=0.0003, OR [95% CI]=0.48 [0.31-0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P=0.001, OR [95% CI]=2.54 [1.39-4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed. CONCLUSIONS: Our results support the association of the HLA complex with the susceptibility to ASSD.