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Resumen Introduccion La implementacion del diagnostico en un solo paso (DUSP) de la infeccion activa por virus de la hepatitis C (VHC) conjuntamente con la incorporacion de alertas informativas ha demostrado que reduce de forma significativa, respecto al diagnostico tradicional, la cifra de pacientes que no eran remitidos para valoracion terapeutica. Metodos A partir de la implementacion en 2018 del DUSP en los servicios de microbiologia de los hospitales del Servicio Gallego de Salud (SERGAS), se identifican y caracterizan de manera retrospectiva los nuevos diagnosticos de infeccion activa por VHC. Resultados En 2018 se identificaron mediante DUSP un total de 258 pacientes con infeccion activa por VHC desconocida (70,2% hombres, mediana de edad de 52 anos) procedentes de consultas de unidades de atencion primaria y especializada en un 54,8% y 39,8%, respectivamente, asi como de otras localizaciones en un 5,4%. De los 258 pacientes, el 81,0% fueron derivados para valoracion terapeutica, con una mediana de 54 dias desde su diagnostico. En el 58,3% de los casos se determino el DUSP mediante carga viral, el genotipo predominante fue el 1a (30,7%), un 52,1% fue tratado y se observo una respuesta viral sostenida en el 93,7% de estos. Conclusion La implementacion en toda Galicia del DUSP de la hepatitis C conjuntamente con alertas informativas ha permitido obtener, en conjunto, tasas de derivacion para tratamiento similares a las obtenidas en otros estudios. Sin embargo, existe una amplia variabilidad entre los distintos centros, que exigen la incorporacion de mejoras, como la formacion o la utilizacion de medidas de rescate para su optimizacion.

Introduction Psoriatic arthritis (PsA) is considered a multifaceted disease, with patients reporting low health-related quality of life (HRQoL). Data on disease burden are substantial and there exists a need for properly designed studies to learn more about the evolution of HRQoL in this condition. This study aims to identify factors associated to HRQoL evolution in PsA patients followed-up in a real-world setting in Spain. Methods We conducted a retrospective longitudinal observational study including incident patients from the rheumatology outpatient clinic of Hospital Clínico San Carlos (Madrid, Spain), diagnosed for the first time of PsA, defined as having received any ICD9/ICD10 diagnosis code of PsA, from 2007 to 2016, and followed-up until loss of follow-up, death, or November 2017. The influence of demographic and clinical variables in baseline HRQoL [assessed with the Rosser Classification Index (RCI)] was analyzed using bivariable and multivariable generalized linear models. The influence of those variables and of treatment-related factors in repeated measures of HRQoL was analyzed using bivariable and multivariable generalized estimating equations (GEE) models nested by patient. Results Two hundred and thirty patients were included in the analysis, with 3384 registered visits. At baseline, older age, a previous diagnosis of obesity, and the presence of enthesitis were significantly associated with worse HRQoL. During follow-up, using an exchangeable working correlation structure, the presence of enthesitis was also associated with worse HRQoL, coefficient (95% CI) − 0.006 (− 0.01 to − 0.002), p = 1.00E−03; conversely, treatment with methotrexate or antimalarials was associated with better HRQoL with 0.007 (0.001–0.014), p = 0.020 and 0.003 (0.001–0.005), p = 3.00E−03, respectively. Conclusions Musculoskeletal manifestations and comorbidities exert a deleterious effect in HRQoL of PsA patients. Therefore, the optimal management of this condition needs to also address these manifestations in order to try to restore the QoL of these patients. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00349-1.

Background: BRCA mutations are responsible for a significant proportion of hereditary breast and ovarian cancers. However, other cancer susceptibility genes are also associated with an increased risk of developing breast cancer (BC). In Mexico, approximately 15% of patients with BC have been identified with BRCA mutations. Despite our growing understanding of BRCA mutations, the contribution and characterization of non-BRCA mutations in Mexican patients with a BC diagnosis remains unknown. We aimed to investigate the spectrum of BC-associated mutations among Mexican patients with BC referred for genetic cancer risk assessment (GCRA) in the multinational Clinical Cancer Genomics Community Research Network (CCGCRN). Methods: Mexican patients with a primary BC who were enrolled in the IRB-approved CCGCRN registry protocol and underwent genetic counseling and multigene panel testing (MGPT) were included. Pathogenic and likely pathogenic variants (PV) in genes associated with increased BC risk were used for analyses. Clinical and demographic characteristics of BRCA and non-BRCA carriers were compared. Results: From December 2012 to February 2020, 725 Mexican patients with BC who had MGPT results with a median age (years) of 41 (range 25-76) were included. 142 (19.6%) patients carried a BC-associated PV. Of these, 98 (69.0%) carried BRCA PVs: 58 in BRCA1 (41.5%) and 40 in BRCA2 (26.7%). PVs in other BC-associated genes (n = 42) accounted for 29.5% of all observed PVs and were distributed as follows: PALB2 (n = 13), CHEK2 (n = 11), RAD51C (n = 6), ATM (n = 3), PTEN (n = 3), TP53 (n = 3), BRIP1 (n = 2), and CDH1(n = 1). Other actionable genes represented 3.5% of all PVs (PMS2 [n = 3]; MSH6 [n = 1]; MSH2 [n = 1]). Suspected founder mutations in Latinas, PALB2 c.2167_2168delAT (n = 5) and CHEK2 c.707T>C (n = 9), represented 33.3% (n = 14/42) of the detected non-BRCA PVs. Mean age at first cancer diagnosis (years) for BRCA and non-BRCA carriers was: 37 (range 26-58) and 42 (range 25-76) (p Citation Format: Yanin Chavarri-Guerra, Cynthia Villarreal-Garza, Gubidxa Gutierrez Seymour, Dione Aguilar y Mendez, Jazmin Arteaga-Vazquez, Servando Cardona-Huerta, Adrian Daneri-Navarro, Azucena del Toro Valero, Alejandro Mohar-Betancourt, Andrés Rodríguez-Faure, Jose Luis Rodriguez-Olivares, Gregorio Quintero Beulo, Danielle Castillo, Kai Yang, Joseph Herzog, Rosa Mejia, Sharon Sand, Jeffrey N Weitzel. The spectrum of germline susceptibility gene variants in Mexican patients with breast cancer (BC): A Prospective Multicenter study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-15.

In this work, a novel optical fiber sensor capable of measuring both the liquid level and its refractive index is designed, manufactured and demonstrated through simulations and experimentally. For this, a silica capillary hollow-core fiber is used. The fiber, with a sensing length of 1.55 mm, has been processed with a femtosecond laser, so that it incorporates four holes in its structure. In this way, the liquid enters the air core, and it is possible to perform the sensing through the Fabry-Perot cavities that the liquid generates. The detection mode is in reflection. With a resolution of 4 μm (liquid level), it is in the state of the art of this type of sensor. The system is designed so that in the future it will be capable of measuring the level of immiscible liquids, that is, liquids that form stratified layers. It can be useful to determine the presence of impurities in tanks. This work was supported by the Ministerio de Economía y Competitividad of Spain (TEC2016-76021-C2-1-R and TEC2016-76021-C2-2-R), the FEDER/Ministerio de Ciencia, Innovación y Universidades and Agencia Estatal de Investigación (PID2019-107270RB-C21 and PID2019-107270RB-C22), the Ministerio de Educación, Cultura y Deporte of Spain (PhD grant FPU2018/02797), and Projects for young researches UPNA 2019. The authors also thank the INESC-Porto colleagues for the fiber sample used in the experiments.

Both systemic inflammation and exacerbations have been associated with greater severity of bronchiectasis. Our objective was to analyze the prognostic value of the peripheral concentration of C-reactive protein (CRP) for the number and severity of exacerbations in patients with bronchiectasis.Patients from the Spanish Bronchiectasis Registry (RIBRON) with valid data on their CRP value (in a clinically stable phase) and valid data on exacerbations during the first year of follow-up were included. A logistic regression analysis was used to evaluate the prognostic value of the CRP concentration (divided into tertiles) with the presence of at least one severe exacerbation or at least two mild-moderate exacerbations during the first year of follow-up.802 patients (mean age: 68.1 [11.1 years], 65% female) were included. Of these, 33.8% and 13%, respectively, presented ≥2 mild-moderate exacerbations or at least one severe exacerbation during the first year of follow-up. The mean value of the CRP was 6.5 (17.6mg/L). Patients with a CRP value between 0.4 and 2.7mg/L (second tertile) and ≥2.7mg/L (third tertile) presented a 2.9 (95%CI: 1.4-5.9) and 4.2 (95%CI: 2.2-8.2) times greater probability, respectively, of experiencing a severe exacerbation than those with0.4mg/L (control group), regardless of bronchiectasis severity or a history of previous exacerbations. However, the CRP value did not present any prognostic value for the number of mild-moderate exacerbations.The CRP value was associated with a greater risk of future severe exacerbations but not with mild or moderate exacerbations in patients with steady-state bronchiectasis.

Resumen Introduccion El Registro Espanol de Bronquiectasias de la SEPAR (RIBRON) comenzo como una plataforma longitudinal de recogida de datos de pacientes con esta enfermedad. El objetivo del presente estudio es describir tanto su funcionamiento, como analizar las caracteristicas de los pacientes con bronquiectasias segun el sexo. Metodos Entre febrero de 2015 y 2019, fueron incluidos 1.912 pacientes adultos diagnosticados de bronquiectasias procedentes de 43 centros. Todos los pacientes presentaron al menos datos completos de 79 variables basicas necesarias y controladas mediante una auditoria externa. Resultados Edad media fue de 67,6 anos (15,2), el 63,9% mujeres. El sintoma mas comun fue la tos productiva en el 78,3%, que fue mucopurulenta-purulenta en el 45,9%. La etiologia mas frecuente fue la postinfecciosa en el 40,4%, siendo idiopaticas en el 18,5%. Pseudomonas aeruginosa fue el microorganismo mas frecuentemente aislado con el 40,4%, el 25,6% en forma de infeccion cronica. El numero anual de agudizaciones leve-moderadas/graves fue de 1,62 (1,9)/0,59 (1,3). El 50% de los pacientes presentaron obstruccion al flujo aereo (el 17% grave). La localizacion mas frecuente fueron los lobulos inferiores. El valor medio del FACED /E-FACED/BSI fue de 2,06 (1,7)/2,67 (2,2)/7,8 (4,5), respectivamente. El 66,7% de los pacientes tomaban corticoides inhalados, el 19,2% macrolidos y el 19,5% antibioticos inhalados. Las mujeres presentaron un perfil de menor gravedad que los varones en terminos clinico-funcionales y etiologicos, pero semejante perfil infeccioso, radiologico y terapeutico. Conclusiones RIBRON representa un excelente mapa de las caracteristicas de las bronquiectasias en nuestro pais. Dos tercios de los pacientes son mujeres que presentaron unas caracteristicas propias, de menor gravedad de la enfermedad.

Background: Non-infectious non-anterior uveitis (NINA) is a sight-threatening condition that often requires immunomodulatory drugs (IMDs) for its management. Objectives: To evaluate the published evidence regarding the use of IMDs in adult patients with NINA uveitis including intermediate (IU) and posterior uveitis (PU), panuveitis (PanU) and macular edema (ME). Methods: We performed a systematic literature review. Search strategies were designed for Medline, Embase, and Cochrane Libraries for articles up to 2019 to evaluate the efficacy and safety of the IMDs. A quality assessment was performed using the Jadad Scale. Results: Nineteen randomized clinical trials were selected from the 1,103 articles retrieved. Characteristics of patients, treatment dosages and outcome measures were heterogeneous. The outcomes most frequently analyzed were visual acuity (VA), macular thickness and vitreous haze (VH). Different IMDs were used at their usual dosages. Methotrexate (MTX), micophenolate mofetil, cyclosporine A (CsA), tacrolimus, adalimumab and sarilumab were effective in NINA uveitis. Rituximab combined with MTX was effective in PU. Interferon-β was superior to MTX, albeit with more adverse events in IU with ME. CsA was similar to cyclophosphamide (Cyc) in Behçet uveitis. Tacrolimus was safer and similar to CsA. Cyc was effective in serpiginoid choroiditis, but when combined with azathioprine in PU, but did not improve VA. Secukinumab did not prevent NINA uveitis recurrences, although intravenously it showed a higher response rate than when used subcutaneously. Daclizumab did not show any benefits in Behçet NINA uveitis. Conclusion: Several IMDs and their combinations can be useful in treating NINA uveitis. The available studies were heterogeneous regarding patient characteristics and outcomes. Sin financiación 5.532 JCR (2020) Q2, 7/34 Rheumatology 1.955 SJR (2020) Q1, 6/122 Anesthesiology and Pain Medicine No data IDR 2020 UEM

Intraductal papillary neoplasm of the bile duct (IPNB) is an uncommon disease which was first included in the World Health Organization classification of neoplasms in 2010. A 64-year-old female was admitted to the hospital because of a hepatic lesion incidentally diagnosed during acute cholangitis. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) showed a well delimited 70 mm mass, with a predominant cystic component and hyperenhancement of papillary internal branching, consistent with a hydatid cyst. However, malignancy could not be excluded. The patient rapidly developed an acute abdomen syndrome, thus precluding a liver biopsy. A new urgent CT was performed to rule out a complication of the cystic lesion. A left hepatectomy was performed and the anatomopathological study confirmed the diagnosis of IPNB with a focus of cholangiocarcinoma therein. During follow up, the patient developed peritoneal carcinomatosis, received palliative chemotherapy and finally died.

ObjectivesTo describe patients with autoimmune inflammatory rheumatic diseases (AIRD) who had COVID-19 disease; to compare patients who required hospital admission with those who did not and assess risk factors for hospital admission related to COVID-19.MethodsAn observational longitudinal study was conducted during the pandemic peak of severe acute respiratory syndrome coronavirus 2 (1 March 2020 to 24 April). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid, Spain with a medical diagnosis of AIRD and with symptomatic COVID-19 were included. The main outcome was hospital admission related to COVID-19. The covariates were sociodemographic, clinical and treatments. We ran a multivariable logistic regression model to assess risk factors for the hospital admission.ResultsThe study population included 123 patients with AIRD and COVID-19. Of these, 54 patients required hospital admission related to COVID-19. The mean age on admission was 69.7 (15.7) years, and the median time from onset of symptoms to hospital admission was 5 (3–10) days. The median length of stay was 9 (6–14) days. A total of 12 patients died (22%) during admission. Compared with outpatients, the factors independently associated with hospital admission were older age (OR: 1.08; p=0.00) and autoimmune systemic condition (vs chronic inflammatory arthritis) (OR: 3.55; p=0.01). No statistically significant findings for exposure to disease-modifying antirheumatic drugs were found in the final model.ConclusionOur results suggest that age and having a systemic autoimmune condition increased the risk of hospital admission, whereas disease-modifying antirheumatic drugs were not associated with hospital admission.

Mean sensitivity (MS) derived from a standard test grid using microperimetry is a sensitive outcome measure in clinical trials investigating new treatments for degenerative retinal diseases. This study hypothesizes that the functional decline is faster at the edge of the dense scotoma (eMS) than by using the overall MS.Multicenter, international, prospective cohort study: ProgStar Study.Stargardt disease type 1 patients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12 months using microperimetry with a Humphrey 10-2 test grid. Customized software was developed to automatically define and selectively follow the test points directly adjacent to the dense scotoma points and to calculate their mean sensitivity (eMS).Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1 years old. At baseline, MS was 10.4 ± 5.2 dB (n = 361), and the eMS was 9.3 ± 3.3 dB (n = 335). The yearly progression rate of MS (1.5 ± 2.1 dB/year) was significantly lower (β = -1.33; P.001) than that for eMS (2.9 ± 2.9 dB/year). There were no differences between progression rates using automated grading and those using manual grading (β = .09; P = .461).In Stargardt disease type 1, macular sensitivity declines significantly faster at the edge of the dense scotoma than in the overall test grid. An automated, time-efficient approach for extracting and grading eMS is possible and appears valid. Thus, eMS offers a valuable tool and sensitive outcome parameter with which to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts.

Deep penetrating nevus (DPN) is an intradermal, sometimes compound benign melanocytic lesion, which involves the reticular dermis, occasionally reaching the subcutis, which can raise concern for melanoma both clinically and histologically. Recently, it has been genetically defined by the combination of MAPK activating and β-catenin activating mutations. We sought to investigate genetic alterations in 2 cases of combined nevi of congenital melanocytic and DPN. Case 1 was a 16-year-old woman with a pigmented lesion on the trunk since birth, which was completely excised. Histopathological examination revealed a combined congenital nevus with a DPN. Comparative genomic hybridization showed no major genetic alterations, except for gain of 6q11.1 and point mutation of B-RAF V600E. Case 2 was a 62-year-old woman with a congenital pigmented lesion on the back. The lesion was diagnosed as a combined nevus of congenital and DPN. Comparative genomic hybridization showed no genetic alterations, and the NRAS Q61K was detected in both components. DPN is in most cases part of a combined nevus. Our cases showed strong and uniform nuclear expression of β-catenin and cyclin D1 in the DPN component suggesting the evolution of the congenital nevus to the DPN clone by acquiring β-catenin activating mutation.

Background: Breast cancer incidence is increasing globally, and a significant proportion of the disease has been linked to genetic susceptibility. Genetic knowledge and skills are essential for achieving optimal cancer care and prevention. However, in low- and middle-income countries the availability of physicians and other providers specializing in cancer genetics is very limited, and cancer genetics is not included in most undergraduate or graduate medical programs. Providing physicians-in-training with education on hereditary breast and ovarian cancer (HBOC) syndromes has the potential to improve the early identification of patients at a higher risk of breast cancer. This study aimed to assess the effect of a short HBOC course given to fellows from a single teaching hospital in Mexico City. Methods: We evaluated the basal practice patterns and knowledge on HBOC among fellows enrolled in internal medicine, general surgery, medical oncology and clinical genetics fellowship programs using a validated cancer genetics questionnaire composed of 13 questions and graded on a 0-100% scale. Fellows received a cancer genetics course (three lectures) from oncologists and geneticists with training in cancer genetics, and changes in knowledge post-course were evaluated using the same questionnaires. Descriptive statistics were utilized to describe the included subjects, and T-tests were used to compare pre and post questionnaire scores. Results: 110 fellows with a median age of 26.9 years (range 24-31) completed the basal questionnaire. 48.9% were enrolled in internal medicine, 21.8% in general surgery, 13.6% in medical oncology and 7.2% in clinical genetics. All respondents reported to routinely interrogate patients about their family history of cancer, and 70% said they had referred patients to the genetics clinic at their institution. The average score on the basal survey was 62% (SD 17). After the cancer genetics course was completed, 85 fellows answered the questionnaire. We found a relative increase in knowledge from pre to post-intervention of 12% (post-intervention average score 70% [SD 14]), which was statistically significant (p Citation Format: Yanin Chavarri Guerra, Hector De la Mora Molina, Rosa Elena Caballero Landinez, Arantxa Lagunas Salazar, Andrea De la O Murillo, Rafael Reyes Arciniega, Enrique Soto Perez de Celis, Jose Luis Rodriguez Olivares, Osvaldo M Mutchinick, Jazmin Arteaga Vazquez. An educational cancer genetics course to increase knowledge on hereditary breast cancer syndromes among physicians-in-training at a teaching hospital in Mexico City [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-15-02.

Cognitive training can improve mental abilities, and a novel method to apply it is trough video games. There is controversy about the effectiveness of commercial video games for brain training, therefore it is necessary to assess the utility of these kinds of games. One quantitative method to assess it is electroencephalography (EEG), a non-invasive technique to study brain activity. This paper explores the use of EEG and video games together to find what are the most used techniques when analyzing the signals by means of a systematic review. From the results of that review two partial contributions were obtained: a taxonomy of techniques to analyze EEG signals, and a ranking of these techniques based on their popularity. The partial contributions were the departure point for working in the main contribution of this paper: eeglib, a Python library for analyzing EEG. The library was tested technically and functionally. The technical test was oriented to assess the correct output of certain algorithms, while the functional one consisted in analyzing data from two different experiments to check the effectiveness of the library.

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder, more frequent in children, characterized by an abnormal accumulation of Langerhans cells admixed with eosinophils, lymphocytes, neutrophils, and macrophages. The clinical presentation is variable and depends on whether a single or multiple organs are affected. Skin lesions are common in LCH (40% of cases) and represent a frequent form of presentation (in up to 80% of cases). Cutaneous manifestations of LCH are highly variable, frequently presenting as crusted papules or scaly seborrheic-like lesions localized in the scalp. We report the first case of a localized acral sclerosing LCH, a new form of LCH. This case highlights the broad and surprising form of presentation of LCH which may be overlooked and can significantly delay its diagnosis. The development of systemic disease may occur months to years after the initial skin presentation. Prompt diagnosis and treatment may prevent progression to systemic disease, as documented in some cases.

Simple Summary In recent years, numerous general and specific reviews about photodynamic therapy and related subtopics have been published. The diversity of reviews is broad, including many different complex topics and disciplines. In this work, we aim to summarize and compile the latest reviews covering the whole photodynamic therapy field. Specifically, the most important reviews of the last two decades are described. Additionally, some of the key issues and main conclusions detected in these reviews are included. We hope this work will serve as a guide and starting point for researchers to delve further into specific topics and formulate research questions. Abstract Photodynamic therapy (PDT) is a promising therapy against cancer. Even though it has been investigated for more than 100 years, scientific publications have grown exponentially in the last two decades. For this reason, we present a brief compendium of reviews of the last two decades classified under different topics, namely, overviews, reviews about specific cancers, and meta-analyses of photosensitisers, PDT mechanisms, dosimetry, and light sources. The key issues and main conclusions are summarized, including ways and means to improve therapy and outcomes. Due to the broad scope of this work and it being the first time that a compendium of the latest reviews has been performed for PDT, it may be of interest to a wide audience.

Simple Summary Photodynamic therapy (PDT) is a promising treatment for cancerous tumours in which light technologies play a crucial role. An attempt to answer a long-standing question about which light source and light parameters are superior is carried out by reviewing the works reporting their effects on PDT outcome. We have identified the light characteristics that primarily affect the PDT process, based on the current evidence found in the literature. This review also examines cutting-edge technologies aiming to surpass the main challenge of PDT: low light penetration through the tissue. Whereas these technologies overcome several initial technical issues, they generate new challenges and pose limitations. We hope this review may be of interest to a broad audience, from bioengineers to clinical oncologists. The overall contribution we hope to make is to identify key roadblocks and provide a broad overview of light-based technologies, to foster improved developments and new perspectives towards enhanced PDT. Abstract Photodynamic therapy (PDT) is a cancer treatment with strong potential over well-established standard therapies in certain cases. Non-ionising radiation, localisation, possible repeated treatments, and stimulation of immunological response are some of the main beneficial features of PDT. Despite the great potential, its application remains challenging. Limited light penetration depth, non-ideal photosensitisers, complex dosimetry, and complicated implementations in the clinic are some limiting factors hindering the extended use of PDT. To surpass actual technological paradigms, radically new sources, light-based devices, advanced photosensitisers, measurement devices, and innovative application strategies are under extensive investigation. The main aim of this review is to highlight the advantages/pitfalls, technical challenges and opportunities of PDT, with a focus on technologies for light activation of photosensitisers, such as light sources, delivery devices, and systems. In this vein, a broad overview of the current status of superficial, interstitial, and deep PDT modalities—and a critical review of light sources and their effects on the PDT process—are presented. Insight into the technical advancements and remaining challenges of optical sources and light devices is provided from a physical and bioengineering perspective.

Introduction: Rheumatic and musculoskeletal diseases (RMDs) have a significant impact on patients’ health-related quality of life (HRQoL) exacerbating disability, reducing independence and work capacity, among others. Predictors’ identification affecting HRQoL could help to place efforts that minimize the deleterious impact of these conditions on patients’ wellbeing. This study evaluates the influence of demographic and clinical predictors on the HRQoL of a cohort of RMD patients, measured using the Rosser classification index (RCI). Methods: We included patients attending the Hospital Clínico San Carlos (HCSC) rheumatology outpatient clinic from 1 April 2007 to 30 November 2017. The primary outcome was the HRQoL assessed in each of the patient’s visits using the RCI. Demographic and clinical variables extracted from a departmental electronic health record (EHR) were used as predictors: RMD diagnoses, treatments, comorbidities, and averaged HRQoL values from previous periods (for this last variable, values were imputed if no information was available). Association between predictors and HRQoL was analyzed using penalized generalized estimating equations (PGEEs). To account for imputation bias, the PGEE model was repeated excluding averaged HRQoL predictors, and common predictors were considered. Discussion: A total of 18,187 outpatients with 95,960 visits were included. From 410 initial predictors, 19 were independently associated with patients’ HRQoL in both PGEE models. Chronic kidney disease (CKD), an episode of prescription of third level analgesics, monoarthritis, and fibromyalgia diagnoses were associated with worse HRQoL. Conversely, the prescription in the previous visit of acid-lowering medication, colchicine, and third level analgesics was associated with better HRQoL. Conclusion: We have identified several diagnoses, treatments, and comorbidities independently associated with HRQoL in a cohort of outpatients attending a rheumatology clinic.

Summary Large-scale mapping of antigens and epitopes is pivotal for developing immunotherapies but challenging, especially for eukaryotic pathogens, owing to their large genomes. Here, we developed an integrated platform for genome phage display (gPhage) to show that unbiased libraries of the eukaryotic parasite Trypanosoma cruzi enable the identification of thousands of antigens recognized by serum samples from patients with Chagas disease. Because most of these antigens are hypothetical proteins, gPhage provides evidence of their expression during infection. We built and validated a comprehensive map of Chagas disease antibody response to show how linear and putative conformation epitopes, many rich in repetitive elements, allow the parasite to evade a buildup of neutralizing antibodies directed against protein domains that mediate infection pathogenesis. Thus, the gPhage platform is a reproducible and effective tool for rapid simultaneous identification of epitopes and antigens, not only in Chagas disease but perhaps also in globally emerging/reemerging acute pathogens., Graphical abstract, Highlights • Genomic shotgun phage display (gPhage) of eukaryotes is feasible and promising. • gPhage allows rapid antigen ID and epitope mapping, including 3D structures. • Conformation epitopes can be identified and validated by using the gPhage platform. • Most Chagas disease antigens are hypothetical proteins rich in repetitive elements., Parasitology; Sequence analysis; Systems biology

Objective: To compare the capacity of various disease activity indices to evaluate changes in function, IL-6 levels, and radiographic progression in early and established rheumatoid arthritis (RA).Methods: Secondary data analysis of a clinical trial assessing the efficacy of tocilizumab in patients with established RA (ACT-RAY) and a longitudinal prospective register of early arthritis (PEARL). Targeted outcomes were changes in physical function, measured with the health assessment questionnaire (HAQ), IL-6 serum levels, and radiographic progression. The “Hospital Universitario La Princesa Index” (HUPI), DAS28 using erythrocyte sedimentation rate and SDAI were the disease activity indices compared. Models adjusted for age and sex were fitted for each outcome and index and ranked based on the R2 parameter and the quasi-likelihood under the independence model criterion.Results: Data from 8,090 visits (550 patients) from ACT-RAY and 775 visits (534 patients) from PEARL were analyzed. The best performing models for HAQ were the HUPI (R2 = 0.351) and SDAI ones (R2 = 0.329). For serum IL-6 levels, the SDAI (R2 = 0.208) followed by the HUPI model (R2 = 0.205). For radiographic progression in ACT-RAY, the HUPI (R2 = 0.034) and the DAS28 models (R2 = 0.026) performed best whereas the DAS28 (R2 = 0.030) and HUPI models (R2 = 0.023) did so in PEARL.Conclusions: HUPI outperformed other indices identifying changes in HAQ and radiographic progression and performed similarly to SDAI for IL-6 serum levels.

Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.

Background Sindbis virus (Alphaviridae) is a plus-strand RNA virus that is dependent on the host cell for replication. Cannabinoid (CB) receptors are found on most human cells, including virally infected cells. Activation of cannabinoid receptors has been shown to alter normal cellular physiology. This study aimed to assess how agonist (ACEA) or antagonists/inverse agonist (AM251) of the cannabinoid receptors would alter the cellular environment and impact Sindbis virus replication. Methods Human hepatoma (Huh7) cells were used as our model for viral replication. Cells were infected with Sindbis virus (SINV) and then treated with CB agonist (ACEA) (10 μM) or antagonist/inverse agonist (AM-251) (10 μM) and virus replication was monitored. A double subgenomic Sindbis virus containing a green fluorescent protein (GFP) reporter gene inserted into a 3′ subgenomic promoter was utilized for these assays to quickly measure viral replication. GFP fluorescent cells were analyzed using flow cytometry to measure the percentage of cells expressing the viral reporter and also quantify the levels of GFP fluorescence. Result Treatment of SINV-infected Huh7 cells with CB1 receptor antagonist/inverse agonist (AM251, 10 μM) resulted in a significant decrease in viral replication, while infected cells treated with a CB1 receptor agonist (ACEA, 10 μM) resulted in a significant increase of viral infection. The data indicates that activation of CB1 receptor by cannabinoids significantly influences the ability of Sindbis virus to replicate in the host cell. Conclusion Blocking CB1 receptor activity with 10 μM AM251 reduced viral replication, but activating the CB1 receptor with 10 μM ACEA resulted in an increase in viral infection. These results indicate cannabinoids may significantly impact a virus replicating in human liver cells. Future confirmation with other viruses and cell lines will be performed to better understand the impact of cannabinoids on viral infections.

Background: Mesenchymal stem cells (MSCs) are a promising treatment of different musculoskeletal diseases including osteoarthritis and rheumatoid arthritis (RA). Results from different approaches in this treatment have been not conclusive. Aim: To analyze factors related to interactions between peripheral blood mononuclear cells (PBMCs) and MSCs and the influence of cellular activation. Materials & methods: PBMCs from RA patients and healthy controls (HC) were obtained. MSCs from bone marrow (BM-MSCs) were obtained from six donors. CD4, CD25, CD69 and CD127 expression was measured by flow cytometry. Repeated measures analysis of variance (ANOVA) models were performed using activation, co-culture with BM-MSCs and time of culture (24 h, 72 h, 6 days) as within-subject variables. Results: PBMCs activated and co-cultured with BM-MSCs showed a lower proportion of CD25-positive and CD25high/CD127low-negative cells in both RA and HC. Additionally, a maintained expression of CD69 was also observed in RA and HC when PBMCs were activated and co-cultured with BM-MSCs. Conclusion: Both PBMC activation grade and RA disease activity influence the immunomodulatory effect of BM-MSCs on T-cell activation.

OBJECTIVE: To perform a cost-effectiveness and budget impact analysis from the perspective of the Spanish public healthcare system (SHS) to compare the number of overnight hospital stays avoided under a community and a hospital pharmacy model due to the administration of intravenous anti-infective therapy (IVAT) at a nursing home with 145 beds. METHODS: Analytical, observational, retrospective cohort study of a nursing home in Galicia (north-west Spain) that switched from a community to a hospital pharmaceutical management model. We compared the number of IVAT administrations, the number of hospital transfers and stays avoided, and mean annual costs avoided by the SHS before and after the switch. Costs were calculated using official SHS rates. RESULTS: The switch from the community to the hospital pharmacy model resulted in 2.8 more IVAT administrations (95% CI, 2.71 to 2.88) and 20.79 fewer overnight hospital stays (95% CI, 20.07 to 21.51) per 100 nursing home beds a month (p

Isolated arthroscopic subacromial decompression (IASD) is a widely used surgical procedure with high success rates. However, up to 25% of patients experience residual pain. It is unclear whether aberrant central nervous system processing of pain as described in fibromyalgia (FM) could have a detrimental effect on outcomes. To test this hypothesis, the authors conducted a retrospective case–control study of patients undergoing IASD. Material and methods Between 2008 and 2015, 26 patients with preoperative diagnosis of fibromyalgia and an IASD procedure were identified. Six patients were lost to follow-up. Each fibromyalgia patient was matched with one control patient (n = 20) recruited from the remainder with IASD. Outcomes were assessed by DASH score (Disability Arm Shoulder and Hand), Constant (CS), relative Constant score (rCS) and Visual Analogue Scale (VAS). Patient satisfaction was determined with a single 2-level question. Failure of the IASD was defined as persistent pain (VAS > 3) at last follow-up. Results The average age of the sample was FM/Control group 51/48, with a mean follow-up of 36/42 months respectively. Both groups exhibited significant clinical improvement in the pain VAS, DASH and rCS at final follow-up (p Mean postoperative scores FM/Control group were: Constant 63.5/74 (p = .07), rCS 82/88 (p = 18), DASH 38.9/20.7 (p = 009), VAS 3.8/2.8 (p = 2). Eighty-five percent of patients in the control group were satisfied with the surgery compared with 55% in the FM group (p = 03). Failure of the procedure was 60% in the FM group, and 30% in the control group (p = .056). Conclusions Fibromyalgia can be considered a prognostic factor of a poor postoperative outcome after an IASD. However the clinical improvement experienced by these patients over their preoperative situation leads us to recommend their surgical treatment when indicated.

Research question Hox genes are involved in limb formation during normal embryological development. Their modulation by circulating maternal oestrogens and androgens determines the length of the second and fourth fingers of the adult hand. Do these same intrauterine hormone levels also determine fertility outcomes in the adult? Design To study the association between the length of the second and fourth fingers of both partners undergoing IVF (as a surrogate of their previous intrauterine exposure to oestrogens and androgens) with treatment outcome after IVF, data corresponding to 256 IVF cycles were analysed. Finger length was normalized to the individual height. Results In the female partner, a longer normalized second finger length of the left (2DLN) hand, reflecting a high intrauterine exposure to oestrogens, was independently and significantly (P = 0.011) associated with obtaining at least one top-quality embryo in a multivariate model. Conversely, in the male partner a longer normalized fourth finger length of the left hand (4DLN), reflecting a high intrauterine exposure to androgens, was independently and significantly (P = 0.032) associated with obtaining at least one top-quality embryo in the same multivariate model. In the female partner, 2DLN was inversely and significantly (P = 0.01) associated with achievement of pregnancy. Conclusions Intrauterine exposure to high levels of oestrogens and androgens in females and males, respectively, predisposes to the production of higher-quality embryos under in-vitro conditions during adulthood. Paradoxically, this also seems to result in a lower pregnancy rate.

OBJECTIVESTo describe persistent symptoms and consequences in Rheumatic and Musculoskeletal diseases (RMD) discharged from the hospital after Covid-19; to assess the roll of autoimmune rheumatic diseases (ARD) compared to and non-autoimmune rheumatic and musculoskeletal diseases (NARD) on persistent symptoms and consequences.METHODSWe performed a cross-sectional observational study. RMD attended at a rheumatology outpatient clinic in Madrid with Covid-19 that required hospital admission were included. The main outcomes were persistence of symptoms and health consequences related to Covid19 after discharge. Independent variable was RMD group (ARD and NARD) and covariates were sociodemographic, clinical, and treatments. We ran a multivariable logistic regression model to assess the risk by RMD group on main outcomes.RESULTSWe included 105 patients and 51.5% had ARD. 68.57% reported at least one persistent symptom. The most frequent were dyspnea, fatigue, and chest pain. 31 patients had consequences. Lung damage was found in 11.4% of the patients, 18% had blood test abnormalities (10% lymphopenia), two died, one developed central retinal vein occlusion and one patient developed optic neuritis. 11 patients required readmission due to Covid-19 problems (16.7% ARD vs 3.9% NARD; p=0.053). No statistically significant differences by RMD groups were found in the final models.CONCLUSIONMany RMD patients have persistent symptoms, similar to other populations. This study also highlights that lung damage is the most frequent consequence. ARD compared to NARD does not seem to differ in terms of persistent symptoms or consequences, although ARD might have a greater number of readmissions due to Covid-19.

Aims: To analyze the association between colchicine prescription and COVID-19-related hospital admissions in patients with rheumatic and musculoskeletal diseases (RMDs). Methods: Patients attending a rheumatology outpatient clinic from a tertiary care center in Madrid, Spain, from 1 September 2019 to 29 February 2020 were included. Patients were assigned as exposed or unexposed based on whether they were prescribed with colchicine in their last visit to the clinic during the 6 months before the start of the observation period. Treatment changes during the observation period were also considered. The primary outcome was COVID-19-related hospital admissions between 1 March and 20 May 2020. Secondary outcome included COVID-19-related mortality. Several weighting techniques for data balancing, based and non-based on the propensity score, followed by Cox regressions were performed to estimate the association of colchicine prescription on both outcomes. Discussion: The number of patients entered in the study was 9379, with 406 and 9002 exposed and unexposed follow-up periods, respectively. Generalized Boosted Models (GBMs) and Empirical Balancing Calibration Weighting (EBCW) methods showed the best balance for COVID-19-related hospital admissions. Colchicine prescription did not show a statistically significant association after covariable balancing ( p-value = 0.195 and 0.059 for GBM and EBCW, respectively). Regarding mortality, the low number of events prevented a success variable balancing and analysis. Conclusion: Colchicine prescription does not play a significant protective or risk role in RMD patients regarding COVID-19-related hospital admissions. Our observations could support the maintenance of colchicine prescription in those patients already being treated, as it is not associated with a worse prognosis. Plain language title: Colchicine influence in COVID-19-related hospital admissions

Aims: In this pandemic, it is essential for rheumatologists and patients to know the relationship between COVID-19 and inflammatory rheumatic diseases (IRDs). We wanted to assess the role of targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARDs) and other variables in the development of moderate-severe COVID-19 disease in IRD. Methods: An observational longitudinal study was conducted during the epidemic peak in Madrid (1 March to 15 April 2020). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid with a medical diagnosis of IRD were included. Main outcome: hospital admission related to COVID-19. Independent variable: ts/bDMARDs. Covariates: sociodemographic, comorbidities, type of IRD diagnosis, glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Incidence rate (IR) of hospital admission related to COVID-19 was expressed per 1000 patient-months. Cox multiple regression analysis was run to examine the influence of ts/bDMARDs and other covariates on IR of hospital admission related to COVID-19. Results: A total of 3951 IRD patients were included (5896 patient-months). Methotrexate was the csDMARD most used. Eight hundred and two patients were on ts/bDMARDs, mainly anti-TNF agents, and Rtx. Hospital admissions related to COVID-19 occurred in 54 patients (1.36%) with an IR of 9.15 (95% confidence interval: 7–11.9). In the multivariate analysis, older, male, comorbidities, and specific systemic autoimmune conditions (Sjögren, polychondritis, Raynaud, and mixed connective tissue disease) had more risk of hospital admissions. Exposition to ts/bDMARDs did not achieve statistical significance. Use of glucocorticoids, NSAIDs, and csDMARDs dropped from the final model. Conclusion: This study provides additional evidence in IRD patients regarding susceptibility to moderate–severe infection related to COVID-19.

Current gold-standard strategies for bone regeneration do not achieve the optimal recovery of bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells—such as mesenchymal stem cells (MSCs)—and bioactive ceramic scaffolds—such as calcium phosphate-based (CaPs) bioceramics—seem promising. The biological properties of MSCs are influenced by the tissue source. This study aims to define the optimal MSC source and construct (i.e., the MSC–CaP combination) for clinical application in bone regeneration. A previous iTRAQ analysis generated the hypothesis that anatomical proximity to bone has a direct effect on MSC phenotype. MSCs were isolated from adipose tissue, bone marrow, and dental pulp, then cultured both on a plastic surface and on CaPs (hydroxyapatite and β-tricalcium phosphate), to compare their biological features. On plastic, MSCs isolated from dental pulp (DPSCs) presented the highest proliferation capacity and the greatest osteogenic potential. On both CaPs, DPSCs demonstrated the greatest capacity to colonise the bioceramics. Furthermore, the results demonstrated a trend that DPSCs had the most robust increase in ALP activity. Regarding CaPs, β-tricalcium phosphate obtained the best viability results, while hydroxyapatite had the highest ALP activity values. Therefore, we propose DPSCs as suitable MSCs for cell-based bone regeneration strategies.

The novel coronavirus disease (COVID-19) is a rapidly spreading pandemic, secondary to severe acute respiratory syndrome coronavirus 2. The severity and the little knowledge that we have of the disease have made us focus mostly on the respiratory symptoms. As we bend the curve, other findings reported in association with COVID-19 become of importance for specialists to recognize. We describe the spectrum of clinicopathologic lesions in the skin that can be the only symptom or the first manifestation of COVID-19 and demonstrate the origin of the virus. We collected 25 patients with skin lesions in this context. We recognized 5 types of cutaneous manifestations including acute acroischemic or chilblain-like lesions (11), purpura palpable (2), exanthemas (9), urticarial eruptions (1), and other lesions (2) that might appear with more unspecific pictures. Chilblain-like lesions were the most common form of presentation, which tend to appear as self-healing, erythematous-necrotic plaques mostly on the feet, in young patients with no systemic symptoms associated. Importantly, we visualized viral particles with electron microscopy in 5 of 13 cases analyzed. In this study, we seek to draw a picture of the spectrum of clinicopathologic lesions that may appear in the skin in the context of COVID-19. Although apparently skin lesions are not correlated with disease severity, it may help in some cases to recognize and control the spread of the infection sooner.

In this work, an experimental analysis of the performance of different types of quasi-randomly distributed reflectors inscribed into a single-mode fiber as a sensing mirror is presented. These artificially-controlled backscattering fiber reflectors are used in short linear cavity fiber lasers. In particular, laser emission and sensor application features are analyzed when employing optical tapered fibers, micro-drilled optical fibers and 50 μm-waist or 100 μm-waist micro-drilled tapered fibers (MDTF). Single-wavelength laser with an output power level of about 8.2 dBm and an optical signal-to-noise ratio of 45 dB were measured when employing a 50 μm-waist micro-drilled tapered optical fiber. The achieved temperature sensitivities were similar to those of FBGs; however, the strain sensitivity improved more than one order of magnitude in comparison with FBG sensors, attaining slope sensitivities as good as 18.1 pm/με when using a 50 μm-waist MDTF as distributed reflector. This work is part of the project PID2019-107270RB, funded by MCIN/ AEI/10.13039/501100011033 and FEDER 'A way to make Europe', the Ministerio de Educación, Cultura y Deporte of Spain (PhD grant FPU2018/02797), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 838143, the Beatriz Galindo BEAGAL18/00116 fellowship, the 'Fundación Caja Navarra' and 'Fundación la Caixa' with the proyect LCF/PR/PR13/51080004 and Projects for young researchers UPNA 2019.

Correction to: Scientific Reports https://doi.org/10.1038/s41598-020-70783-8, published online 14 August 2020 This Article contains a typographical error in the Acknowledgements section. “the Ministerio de Economía y Competitividad of Spain (TEC2013-47342-C2-2-R)” should read: "the Ministerio de Economía y Competitividad of Spain (TEC2016-77242-C3-1-R)" This work was supported by the Comunidad de Madrid and FEDER Program (S2018/NMT-4326), the Ministerio de Economía y Competitividad of Spain (TEC2013-47342-C2-2-R and TEC2016-76021-C2-2-R), the FEDER/Ministerio de Ciencia, Innovación y Universidades and Agencia Estatal de Investigación (RTC2017-6321-1, PID2019-109072RB-C31 and PID2019-107270RB-C21). The authors also acknowledge the support by the Ministry of National Defense of Poland (GBMON/13-995/2018/WAT), Military University of Technology (Grant no. 23-895).

In this work, a novel technique to create positive-negative tunable liquid crystal lenses is proposed and experimentally demonstrated. This structure is based on two main elements, a transmission line acting as a voltage divider and concentric electrodes that distribute the voltage homogeneously across the active area. This proposal avoids all disadvantages of previous techniques, involving much simpler fabrication process (a single lithographic step) and voltage control (one or two sources). In addition, low voltage signals are required. Lenses with switchable positive and negative focal lengths and a simple, low voltage control are demonstrated. Moreover, by using this technique other optical devices could be engineered, e.g. axicons, Powell lenses, cylindrical lenses, Fresnel lenses, beam steerers, optical vortex generators, etc. For this reason, the proposed technique could open new venues of research in optical phase modulation based on liquid crystal materials.