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Marc Miravitlles,1 Miguel Roman-Rodríguez,2,3 Xavier Ribera,4 John Ritz,5 José Luis Izquierdo6,7 On behalf of OPTI investigator’s group1Pneumology Department, Hospital Universitari Vall d´Hebron/Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 2Centro de Salud Dra. Teresa Pique, Mallorca, Spain; 3Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Mallorca, Spain; 4Boehringer Ingelheim España, Sant Cugat del Vallés, Barcelona, Spain; 5Syneos Health - Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 6Department of Medicine and Medical Specialties, Universidad de Alcalá, Madrid, Spain; 7Pneumology Department, Hospital Universitario de Guadalajara, Guadalajara, SpainCorrespondence: Marc Miravitlles,Pneumology Department, Hospital Universitari Vall d’Hebron, P. Vall d’Hebron 119-129, Barcelona, ES– 08035, Spain, Email marcm@separ.esPurpose: Inhaled corticosteroids (ICS) are frequently used to treat chronic obstructive pulmonary disease (COPD) outside the current recommendations. Our aim was to describe ICS use in COPD patients and to identify factors associated with ICS use among COPD patients treated within primary care in Spain.Patients and Methods: This was a cross-sectional, non-interventional and multicenter study of patients with COPD treated in primary care. Patient characteristics and exacerbations were described in terms of ICS use among the overall cohort, and among those with spirometry confirmed COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio < 70%). Multivariable logistic regression was used to identify factors associated with ICS use.Results: A total of 901 patients were included, of which 47.9% (n = 432) were treated with ICS. A total of 240 patients (26.6%) experienced moderate/severe exacerbations in the prior year, while 309 (34.3%) during the previous two years. History of asthma totaled 11.6% (n = 105). The most frequent phenotype was non-exacerbator (51.6%), and the proportion of patient with moderate or severe exacerbations was significantly higher among ICS treated patients compared to non-treated: 37.5% versus 16.6% during the previous year (p < 0.001), and 46.8% versus 22.8% during the previous 2-years (p < 0.001), respectively. Patient characteristics were similar among spirometry confirmed patients and the overall population. Factors significantly associated with ICS use were a history of asthma (OR = 4.39, 95% CI: 2.67– 7.26), the presence of moderate or severe exacerbations in the last year (OR = 2.52, 95% CI: 1.81– 3.49), followed by higher mMRC and higher CAT score.Conclusion: Nearly half of patients in primary care in Spain are treated with ICS, despite most of them being non-exacerbators. History of asthma, exacerbations, and worse dyspnea and CAT scores are associated with ICS use.Keywords: chronic obstructive pulmonary disease, primary care, inhaled corticosteroids, exacerbations

Budesonide; Transplant; Nephropathy Budesonida; Trasplante; Nefropatía Budesonida; Trasplantament; Nefropatia

Objectives Idiopathic focal segmental glomerulosclerosis (FSGS) has been linked to immunological and inflammatory response dysregulations. The aim of this study was to find endotypes of FSGS patients using a cluster (CL) analysis based on inflammatory and immunological variables, and to analyse whether a certain endotype is associated with response to treatment with corticosteroids. Methods This prospective observational study included patients with idiopathic FSGS diagnosed by kidney biopsy. Serum levels of soluble interleukin (IL)-1 receptor, tumoural necrosis factor alpha, Interferon gamma (IFNγ), IL-6, IL-17, IL-12, IL-23, IL-13, IL-4, IL-5, IL-6, haemopexin (Hx), haptoglobin (Hgl), soluble urokinase-type plasminogen activator receptor (suPAR) and urinary CD80 (uCD80) were measured with enzyme-linked immunosorbent assay or nephelometry. T-helper lymphocyte populations and T-regulatory lymphocytes were analysed by flow cytometry. A factorial analysis followed by a k-means CL analysis was performed. Results A total of 79 FSGS patients were included. Three CLs were identified. CL1 (27.8%) included IL-12, IL-17, IL-23 and a T helper 17 (Th17) pattern. CL2 (20.2%) included IL-4, IL-5, IL-13, immunoglobulin E and Th2 pattern. CL3 (51.8%) included IL-6, Hx, Hgl, suPAR and uCD80. There were no differences in age, gender, kidney function, albumin or proteinuria among CLs. About 42/79 patients (53.1%) showed cortico-resistance. The prevalence of cortico-resistance was significantly lower in CL2 (4/16, 25%) than in CL1 (16/26, 72.7%) and CL3 (22/41, 53.7%) (P = 0.018), with no significant differences between CLs 1 and 3 (P = 0.14). Conclusions Patients with FSGS and indistinguishable clinical presentation at diagnosis were classified in three distinct CLs according to predominant Th17, Th2 and acute inflammatory responses that display differences in clinical response to treatment with corticosteroids., Graphical Abstract

Background Activation of parietal–epithelial cells (PECs) with neo-expression of CD44 has been found to play a relevant role in the development of focal and segmental glomerulosclerosis (FSGS). The aim of this study was to analyse whether the expression of CD44 by PECs in biopsies of minimal change disease (MCD) is associated with the response to corticosteroids, with kidney outcomes and/or can be considered an early sign of FSGS. Methods This multicentric, retrospective study included paediatric and adult patients with MCD. Demographic, clinical and biochemical data were recorded, and biopsies were stained with anti-CD44 antibodies. The association between PECs, CD44 expression and the response to corticosteroids, and kidney outcomes were analysed using logistic, Kaplan–Meier and Cox regression analyses. Results A total of 54 patients were included: 35 (65%) Conclusions In patients with a light microscopy pattern of MCD, CD44-positive staining of PECs is associated with a higher prevalence of steroid resistance and worse kidney outcomes, and can be considered an early sign of FSGS.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, To assess whether corticosteroids improve prognosis in patients with AS-AIH, and to identify factors at therapy initiation and during therapy predictive of the response to corticosteroids. Methods: This was a retrospective cohort study including all patients with AS-AIH admitted to 13 tertiary centres from January 2002 to January 2019. The composite primary outcome was death or liver transplantation within 90 days of admission. Kaplan–Meier and Cox regression methods were used for data analysis. Results: Of 242 consecutive patients enrolled (mean age [SD] 49.7 [16.8] years), 203 received corticosteroids. Overall 90-day transplant-free survival was 61.6% (95% confidence interval [CI] 55.4–67.7). Corticosteroids reduced the risk of a poor outcome (adjusted hazard ratio [HR] 0.25; 95% CI 0.2–0.4), but this treatment failed in 30.5%. An internally validated nomogram composed of older age, MELD, encephalopathy and ascites at the initiation of corticosteroids accurately predicted the response (C-index 0.82; [95% CI 0.8–0.9]). In responders, MELD significantly improved from days 3 to 14 but remained unchanged in non-responders. MELD on day 7 with a cut-off of 25 (sensitivity 62.5%[95% CI: 47.0–75.8]; specificity 95.2% [95% CI: 89.9–97.8]) was the best univariate predictor of the response. Prolonging corticosteroids did not increase the overall infection risk (adjusted HR 0.75; 95% CI 0.3–2.1). Conclusion: Older patients with high MELD, encephalopathy or ascites at steroid therapy initiation and during treatment are unlikely to show a favourable response and so prolonged therapy in these patients, especially if they are transplantation candidates, should be avoided, This study was supported in part by grants from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, number PI20/01302, awarded to Agustín Albillos and number PI 21/01310, awarded to Luis Téllez. CIBEREHD is funded by the Instituto de Salud Carlos III using grants cofinanced by the European Development Regional Fund “A way to achieve Europe” (EDRF). María Carlota Londoño received support from the Plan Nacional de I+D+I co- funded by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER-"Una manera de Hacer Europa") (PI17/00955)

MPOC; Asma; Pronòstic EPOC; Asma; Pronóstico COPD; Asthma; Prognosis Although chronic obstructive pulmonary disease (COPD) and asthma are well-characterized diseases, they can coexist in a given patient. The term asthma–COPD overlap (ACO) was introduced to describe patients that have clinical features of both diseases and may represent around 25% of COPD patients and around 20% of asthma patients. Despite the increasing interest in ACO, there are still substantial controversies regarding its definition and its position within clinical guidelines for patients with obstructive lung disease. In general, most definitions indicate that ACO patients must present with non-reversible airflow limitation, significant exposure to smoking or other noxious particles or gases, together with features of asthma. In patients with a primary diagnosis of COPD, the identification of ACO has therapeutic implication because the asthmatic component should be treated with inhaled corticosteroids and some studies suggest that the most severe patients may respond to biological agents indicated for severe asthma. This manuscript aims to summarize the current state-of-the-art of ACO. The definitions, prevalence, and clinical manifestations will be reviewed and some innovative aspects, such as genetics, epigenetics, and biomarkers will be addressed. Lastly, the management and prognosis will be outlined as well as the position of ACO in the COPD and asthma guidelines.

Malalties inflamatòries; Ulls; Pacients adults Enfermedades inflamatorias; Ojos; Pacientes adultos Inflammatory diseases; Eyes; Adult patients La uveïtis és una malaltia inflamatòria que afecta a capa intermèdia de l’ull o úvea (iris, cosciliat i coroide), i que molts cops també pot afectar a estructures adjacents. La malaltia cursa amb símptomes d’inflamació intraocular greu, dolor i afectació de la visió, i els pacients tenen risc de desenvolupar dany ocular permanent i ceguesa. S’estima que la incidència de la uveïtis és de 45 casos per 100.000 habitants, i la prevalença oscil·la segons els diferents estudis entre 70-140 casos per 100.000 habitants. La uveïtis no infecciosa (UNI) és el resultat d’una resposta inflamatòria anormal i suposa un 70% de tots els casos d’uveïtis en els països occidentals. La uveïtis intermèdia, posterior i la panuveïtis, a partir d’ara uveïtis no infecciosa no anterior (UNINA); són menys comunes que la uveïtis anterior (1 de cada 4 diagnòstics d’UNI), però són més greus i tenen més risc de presentar una pèrdua de visió. Uveitis is an inflammatory disease that affects the intermediate layer of the eye or uvea (iris, cosmylate and choroid), and that many times it can also affect adjacent structures. The illness attends symptoms of severe intraocular inflammation, pain and vision impairment, and patients are at risk of developing permanent and blind eye damage. It is estimated that the incidence of uveitis is 45 cases per 100,000 inhabitants, and the prevalence oscillates according to the different studies between 70-140 cases per 100,000 inhabitants. Uveits not Infectious (UNI) is the result of an abnormal inflammatory response and accounts for 70% of all cases of uveitis in western countries. Intermediate uveitis, posterior and peanveitis, from now infectious uveitis no previous (UNINA); They are less common than the previous uveitis (1 out of 4 UNI diagnostics), but they are more serious and are more likely to experience loss of vision La uveítis es una enfermedad inflamatoria que afecta a capa intermedia del ojo o úvea (iris, cosciliat y coroides), y que muchas veces también puede afectar a estructuras adyacentes. La enfermedad cursa con síntomas de inflamación intraocular grave, dolor y afectación de la visión, y los pacientes tienen riesgo de desarrollar daño ocular permanente y ceguera. Se estima que la incidencia de la uveítis es de 45 casos por 100.000 habitantes, y la prevalencia oscila según los diferentes estudios entre 70-140 casos por 100.000 habitantes. La uveítis no infecciosa (UNI) es el resultado de una respuesta inflamatoria anormal y supone un 70% de todos los casos de uveítis en los países occidentales. La uveítis intermedia, posterior y la panuveïtis, a partir de ahora uveítis no infecciosa no anterior (uniendo); son menos comunes que la uveítis anterior (1 de cada 4 diagnósticos de UNI), pero son más graves y tienen más riesgo de presentar una pérdida de visión