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Introducción y objetivos: La evaluación actual de la insuficiencia cardiaca (IC) aguda no permite predecir adecuadamente su evolución. La bioimpedancia eléctrica (BI) permite conocer el estado de volemia, hasta ahora solo con equipos fijos. Hemos desarrollado y validado un dispositivo portátil e inalámbrico para medir la BI en el tobillo (IVOL). El objetivo del estudio es conocer el valor pronóstico a largo plazo de la medición puntual de la BI con IVOL en pacientes con IC aguda. Métodos: Estudio de cohorte prospectivo de pacientes no seleccionados ingresados por IC aguda en un hospital de tercer nivel. Se analizó la asociación entre la BI y diferentes variables (clínicas, analíticas y ecocardiográficos) al ingreso y evolución clínica. Resultados: Se incluyeron 76 pacientes (edad media 66,1 anos, ˜ 71,1% varones, 68,4% hipertensos, 34,2% diabéticos, NT-ProBNP medio: 7.103 pg/ml). De ellos, el 52,6% con fracción de eyección del ventrículo izquierdo (FEVI) no preservada (< 50%) y el 56,6% con disfunción del ventrículo derecho (VD). El 26,3% fallecieron durante un seguimiento medio de 35,8 meses. La supervivencia en pacientes con BI ≤ 21,8 fue menor, globalmente, y en los subgrupos de pacientes sin FEVI preservada y con disfunción del VD; p < 0,008). En el análisis multivariante una BI ≥ 21,8 fue un factor independiente de supervivencia (HR: 0,242; IC 95%: 0,86-0,681; p = 0,007). Conclusiones: Los valores de la BI medidos con IVOL pueden ser un predictor independiente de mortalidad a largo plazo en pacientes hospitalizados por IC aguda. Este valor pronóstico se mantiene en pacientes con FEVI no preservada y con disfunción ventricular derecha.

Background Pneumocytis jirovecii infection in preterm newborns has recently been associated with neonatal respiratory distress syndrome and bronchopulmonary dysplasia. Changes in the bacterial microbiota of the airways have also been described in infants with bronchopulmonary dysplasia. However, until now there has been no information on the airway mycobiota in newborns. The purpose of this study was to describe the airway mycobiota in term and preterm newborns and its possible association with respiratory distress syndrome. Methods Twenty-six matched preterm newborns with and without respiratory distress syndrome were studied, as well as 13 term babies. The identification of the fungal microbiota was carried out using molecular procedures in aspirated nasal samples at birth. Results The ascomycota phylum was identified in 89.7% of newborns, while the basidiomycota phylum was found in 33.3%. Cladosporium was the predominant genus in both term and preterm infants 38.4% vs. 73% without statistical differences. Candida sake and Pneumocystis jirovecii were only found in preterm infants, suggesting a potential relationship with the risk of prematurity. Conclusions This is the first report to describe the fungal microbiota of the airways in term and preterm infants with and without respiratory distress syndrome. Although no differences have been observed, the number of cases analyzed could be small to obtain conclusive results, and more studies are needed to understand the role of the fungal microbiota of the airways in neonatal respiratory pathology.

Introducción: es muy relevante conocer el pronóstico de la insuficiencia cardiaca (IC), tanto a corto como a medio plazo. En la actualidad no existen modelos pronósticos ni escalas predictivas que resulten fiables en todos los casos de IC y la mayoría se ha desarrollado para IC crónica. Por otra parte, la información sobre la evolución del perfil y manejo clínico de los pacientes hospitalizados por IC de novo en España es limitada. Objetivos generales: (i) describir la evolución en las dos últimas décadas de las características clínicas y comorbilidad de los pacientes hospitalizados por un primer episodio de IC, identificar los cambios en la adecuación de indicaciones sobre diagnóstico y tratamiento y el impacto de los cambios en el espectro clínico y el manejo de la IC sobre el pronóstico de la enfermedad a un año de; (ii)realizar la validación externa del modelo PREDICE-SCORE desarrollado para predecir la mortalidad a un año en pacientes hospitalizados por un primer episodio de IC. Método: el estudio PREDICE (PREdicción Desenlaces Insuficiencia Cardiaca en España, FIS 06-90243; FIS07/0945; SAS 357-06) se diseñó como un estudio observacional multicéntrico (Hospitales Virgen del Rocío y de Valme de Sevilla; 12 de octubre de Madrid). Se incluyeron un total de 780 pacientes hospitalizados por un primer episodio de IC según los criterios de Framingham en dos periodos de tiempo, denominados: (i) cohorte retrospectiva 2005 (600 pacientes reclutados entre 2004 y 2008); (ii) cohorte prospectiva 2015 (180 pacientes reclutados entre 2013-2015). En ambos casos seguimiento durante un año. Resultados principales: la comorbilidad medida por un índice de Charlson >2 fue del 12,8% en la cohorte y del 90% en la cohorte de 2015 (p<0,001) El diagnóstico de IC con fracción de eyección reducida se obtuvo en un 2,9% de los pacientes de la cohorte 2005 y un 37% de la cohorte 2015 (p< 0,001). La indicación de betabloqueante al alta fue del 31,3% en la cohorte 2005 y el 50,6% en la cohorte

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Investigating the role of host genetic factors in COVID-19 severity and susceptibility can inform our understanding of the underlying biological mechanisms that influence adverse outcomes and drug development1,2. Here we present a second updated genome-wide association study (GWAS) on COVID-19 severity and infection susceptibility to SARS-CoV-2 from the COVID-19 Host Genetic Initiative (data release 7). We performed a meta-analysis of up to 219,692 cases and over 3 million controls, identifying 51 distinct genome-wide significant loci—adding 28 loci from the previous data release2. The increased number of candidate genes at the identified loci helped to map three major biological pathways that are involved in susceptibility and severity: viral entry, airway defence in mucus and type I interferon. (extract)

We assessed the impact of the first wave of COVID-19 pandemic on non-COVID hospital admissions, non-COVID mortality, factors associated with non-COVID mortality, and changes in the profile of non- COVID patients admitted to hospital. We used the Spanish Minimum Basic Data Set with diagnosis grouped according to the Diagnostic Related Groups. A total of 10,594 patients (3% COVID-19; 97% non-COVID) hospitalised during the first wave in 2020 (27-February/07-June) were compared with those hospitalised within the same dates of 2017–2019 (average annual admissions: 14,037). We found a decrease in non-COVID medical (22%) and surgical (33%) hospitalisations and a 25.7% increase in hospital mortality among non-COVID patients during the first pandemic wave compared to prepandemic years. During the officially declared sub-period of excess mortality in the area (17-March/20- April, in-hospital non-COVID mortality was even higher (58.7% higher than the pre-pandemic years). Non-COVID patients hospitalised during the first pandemic wave (compared to pre-pandemic years) were older, more frequently men, with longer hospital stay and increased disease severity. Hospitalisation during the first pandemic wave in 2020, compared to hospitalisation during the prepandemic years, was an independent risk factor for non-COVID mortality (HR 1.30, 95% CI 1.07–1.57, p = 0.008), reflecting the negative impact of the pandemic on hospitalised patients.

Heart failure (HF) is a severe disease and one of the most important causes of death in our society nowadays. A significant percentage of patients hospitalized for decompensation of heart failure are readmitted after some weeks or months due to an expected bad and uncontrolled HF evolution due to the lack of the patient supervision in real time. Herein is presented a straightforward electric model useful for volume leg section calculus based on the bioimpedance test as a way to assist with the acute HF patient’s supervision. The method has been developed for time-evolution edema evaluation in patients’ corresponding legs. The data are picked up with a wearable device specifically developed for acute heart failure patients. As an initial step, a calibration method is proposed to extract the extracellular volume component from bioimpedance measurements done in healthy subjects, and then applied to unhealthy ones. The intra- and extracellular resistance components are calculated from fitted Cole–Cole model parameters derived from BI spectroscopy measurements. Results obtained in a pilot assay, with healthy subjects and heart failure subjects, show sensitivities in leg volume [mL/Ω], with much lower values for healthy than in unhealthy people, being an excellent biomarker to discriminate between both. Finally, circadian cycle evolution for leg volume has been measured from the bioimpedance test as an extension of the work, enabling an alternative parameter for the characterization of one day of human activity for any person.

Objetivos. El presente proyecto parte de la hipótesis de que un programa docente basado en la enseñanza integrada y en el aprendizaje basado en problemas constituye una forma innovadora de docencia que alcanza una mayor satisfacción en el alumnado sin disminuir el rendimiento académico. Método. Durante el curso académico 2018-19, los alumnos de cuarto curso de medicina del Campus Virgen del Rocío participaron en una implementación de una docencia integrada basada en resolución de problemas integrando tres asignaturas complementarias: patología médica de sistemas, patología quirúrgica de sistemas y diagnóstico por la imagen. Los alumnos se dividieron en dos grupos, uno sin intervención como grupo control. Tras la finalización de la asignatura, la satisfacción del alumnado fue evaluada mediante una encuesta, junto con el análisis de las calificaciones finales entre ambos grupos. Resultados. El plan docente se implementó sin grandes incidencias. La encuesta de satisfacción mostró que esta satisfacción fue elevada con un 76% de los alumnos que estaban bastante o muy satisfechos. Sin embargo, no había una aceptación uniforme para impartir la docencia exclusivamente en este formato. No hubo diferencias en las calificaciones finales entre los grupos de intervención y control Conclusiones. Los resultados avalan el uso de la enseñanza basada en resolución de problemas como método complementario la docencia tradicional sin detrimento de las calificaciones finales, Objectives. The present project is based on the hypothesis that a teaching program based on integrated teaching and problem-based learning constitutes an innovative form of teaching that achieves greater student satisfaction without reducing academic performance. Method. During the 2018-19 academic year, fourth-year medical students at the Virgen del Rocío Campus participated in an implementation of integrated teaching based on problem-solving integrating three complementary subjects: systems medical pathology, systems surgical pathology, and diagnostic imaging. The students were divided into two groups, one without intervention as a control group. After completion of the course, student satisfaction was evaluated by means of a survey, together with the analysis of final grades between the two groups. Results. The teaching plan was implemented without major incidents. The satisfaction survey showed that satisfaction was high with 76% of the students being fairly or very satisfied. However, there was no uniform acceptance for teaching exclusively in this format. There were no differences in the final ratings between the intervention and control groups. Conclusions. The results support the use of problem-based teaching as a complementary method to traditional teaching without detriment to final grades.

Objetivos: Aunque en la fibrilación auricular (FA) de larga duración el control del ritmo no ha demostrado beneficios a largo plazo sobre el control de la frecuencia, en la FA de inicio reciente las evidencias disponibles son escasas. El objetivo de esta Tesis es evaluar en pacientes con FA de reciente comienzo atendidos en los servicios de urgencias hospitalarios (SUH) de España las estrategias de control del ritmo utilizadas, su adecuación y beneficios clínicos asociados. Metodología: estudio multicéntrico, observacional, transversal con recogida de datos prospectiva y estandarizada en el que se incluyeron pacientes consecutivos con FA atendidos en 2011 en 124 SUH representativos del sistema sanitario español del registro HERMES-AF (estrategias de manejo en el servicio de urgencias hospitalario de la FA). Resultados: En un primer estudio (beneficio clínico) se incluyeron 421 pacientes. Se eligió estrategia de control del ritmo en el 83,6% y de frecuencia en el 16,4%, con una efectividad global del 84% y el 97%, respectivamente. El control de los síntomas se logró en el 94,1% de los pacientes y se asoció con frecuencia cardiaca ≤110 tras el tratamiento (razón de riesgo, OR: 14, 35) y estrategia de control del ritmo (OR: 2,78). El alta hospitalaria se asoció de forma independiente con la estrategia de control del ritmo (OR = 2,22). En un segundo estudio (estrategias de control del ritmo) se incluyeron 337 pacientes. Se optó por cardioversión farmacológica en el 92,3%, y eléctrica en el 15%. Se obtuvo ritmo sinusal (RS) en el 82,5% y alivio de síntomas en el 94%, con una tasa de efectos adversos del 0,9%, ninguno grave. Amiodarona se asoció a menor tasa de RS al alta (OR: 0,44), al contrario que cardioversión eléctrica (OR: 4,0). Los fármacos I-C se asociaron con mayor proporción de altas en <6 h (OR: 2,6) y amiodarona con más estancias prolongadas (OR: 2,7). Finalmente, en el tercer estudio (estrategias para mantener al alta el ritmo sinusal) se incluyeron 449 pacie

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

We conducted a pilot study of patients with cystic fibrosis (CF) to assess intra-family transmission of P. jirovecii and compare it with data on other prevalent pathogens such as P. aeruginosa and S. pneumoniae, in which respiratory transmission has already been documented. Oral swab samples from 10 patients with CF and 15 household members were collected at baseline and 2 weeks later. P. aeruginosa and S. pneumoniae were assessed using standardized culture methods and PCR, and P. jirovecii was assessed using real and nested PCR, genotyping the positive samples by direct sequencing. P. aeruginosa cultures were positive for 7/10 (70%) of patients with CF at baseline and was identified by PCR in 8/10 (80%) of cases at baseline and 2 weeks later. S. pneumoniae cultures were negative for all patients, but the microorganism was identified by PCR in two cases. P. jirovecii was detected by real time and nested PCR in 5/10 (50%) of the patients at the two time points. In the household members, P. aeruginosa and P. jirovecii were identified in 7/15 (46.7%), and S. pneumoniae was identified in 8/15 (53,3%). The concordance of positive or negative pairs of patients with CF and their household members was 33.3% (5/15) for P. aeruginosa, 46.7% (7/15) for S. pneumonia and 93.3% (14/15) for P. jirovecii. The concordance for P. jirovecii genotypes among five pairs with available genotype was 100%. This study suggests for the first time the possible transmission of Pneumocystis in the home of patients with CF, indicating that patients and their household members are reservoirs and possible sources of infection.

En el contexto de la biomedicina del siglo XXI, el internista continúa siendo uno de los principales vertebradores de la asistencia sanitaria, con una gran capacidad de adaptación a los escenarios clínicos cambiantes. La amplia formación clínica y polivalencia, y la visión integral e integradora del hombre enfermo que les caracteriza, los sitúan siempre en la vanguardia de los avances en Medicina. Con una vocación claramente holística, la contribución de la medicina interna a la epidemiología clínica puede considerarse, al menos tan relevante como la de otras áreas de la medicina, y la interrelación entre ambas disciplinas una asociación de carácter claramente simbiótico.

Objective: Pneumocystis pneumonia remains a major opportunistic infection in immunocompromised patients worldwide. Colonization with Pneumocystis jirovecii has recently gained attention as an important issue for understanding the complete cycle of human Pneumocystis infection. P. jirovecii Superoxide Dismutase (SOD) gene could be a molecular target with high clinical relevance, but the epidemiological information about SOD genotypes distribution is scarce. The aim of this work was to provide information about the prevalence of genotypes of Pneumocystis SOD among Spanish patients and to describe possible differences between colonized and Pneumocystis pneumonia patients. Methods: we developed a cross-sectional study analyzing broncho-alveolar lavage fluid samples from 30 Pneumocystis pneumonia patients, 30 colonized patients, and 20 controls using a nested PCR protocol designed to amplify the sodA gene of P. jirovecii. The diagnostic yield of SOD Nested PCR was evaluated against the routine practice of mtLSUrRNA Nested PCR, which is considered the gold standard. Results: SOD locus was amplified in 90% of Pneumocystis pneumonia patients, 10% of colonized patients, and none of controls. Genotype SOD1 was observed in 11 cases (52.4%) and genotype SOD2 in 10 cases (47.6%). Genotype SOD2 was observed only in Pneumocystis pneumonia patients while the genotype SOD1 was observed in both colonized and Pneumocystis pneumonia patients. Conclusions: This study provides epidemiological information about SOD genotypes distribution in Spain, showing a low genetic diversity and a predominant presence of genotype SOD1 in colonized patients. SOP Nested PCR was more sensitive and accurate assay in Pneumocystis pneumonia patients than in colonized individuals.

Purpose: Heart failure (HF) is a chronic, frequent and disabling condition but with a modifiable course and a large potential for improving. The aim of this study was to validate the two available clinical prediction rules for mortality at one year in patients with primo- hospitalization for decompensated HF: PREDICE and AHEAD. The secondary aim was to evaluate in our setting the changes in the clinical pattern of HF in the last decade in patients hospitalized for a first episode of the disease. Patients and methods: A prospective multicenter cohort study, which included 180 patients hospitalized with “de novo” HF was conducted to validate the PREDICE score. Calibration and discrimination measurements were calculated for the PREDICE model and the PREDICE score (using the validation cohort of the PREDICE) and the AHEAD score (using both the development and the validation cohort of the PREDICE). Results: For the PREDICE models, the area under the curve (AUC) was 0.68 (95% confidence interval [CI]: 0.57–0.79) and the calibration slope 0.65 (95% CI: 0.21–1.20). For the PREDICE score AUC was 0.59 (95% CI: 0.47–0.71) and slope 0.42 (95% CI: −0.20–1.17). For the AHEAD score the AUC was 0.68 (95% CI: 0.62–0.73) and slope 1.38 (95% CI: 0.62–0.73) when used the development cohort of PREDICE and the AUC was 0.58 (95% CI: 0.49–0.67), and slope 0.68 (95% CI: −0.06 to 1.47) when used its validation cohort. Conclusion: The present study shows that the two risk scores available for patients with primo-hospitalization for decompensated HF (PREDICE and AHEAD) are not currently valid for predicting mortality at one-year. In our setting the clinical spectrum of hospitalized patients with new-onset HF has been modified over time. The study underscores the need to validate the prognostic models before clinical implementation.

Objective: The information about the epidemiology of Pneumocystis pneumonia (PcP) in Europe is scarce, and in Spain there are only data nationwide on patients with HIV infection. This study has been carried out with the aim of knowing in our country the current epidemiological spectrum and the risk factors of PcP. Methods: Observational, descriptive transversal study that included all patients admitted in Spain with diagnosis upon discharge of PcP registered in the National Health System’s Hospital Discharge Records Database of Spain, between 2008 and 2012. Results: Four thousand five hundred and fifty four cases of PcP were reported, 1,204 (26.4%) in HIV-negative patients. During the study period, mean annual incidence (cases per million) was 19.4, remaining globally stable, increasing from 4.4 to 6.3 in HIV-negative patients and decreasing from 15.5 to 13.4 among HIV-infected patients. Risk factors were identified in 85.5% of HIV-negative cases, the most frequent being hematological neoplams (29%), chronic lung diseases (15.9%), and non-hematological cancers (14.9%). Mean mortality and hospitalization cost were high (25.5% and 12,000 euros, respectively). Conclusions: The results of this first nationwide study in Spain allow a change in the misconception that, after the AIDS epidemic, PcP is an infrequent disease, showing that today it is an emerging problem in patients without HIV infection. These findings underlines the need for increased efforts toward a better characterization of risk groups to improve prophylactic strategies and reduce the burden of disease.

BRIEF SUMMARY OF DOCTORAL THESIS Tittle: Pneumocystis jirovecii colonization in patients in treatment with anti-TNF drugs Authors: Conferring a doctor's degree: Isabel Martín Garrido Directors: Enrique Calderón Sandubete MD, PhD. José Manuel Varela Aguilar MD, PhD. Francisco Javier Medrano Ortega MD, PhD. Tutor: Proffesor José Ricardo Villar Ortiz Introduction: Pneumocystis pneumonia (PcP) is an important opportunistic infection, with high mortality rate, not only in patients with acquired immunodeficiency syndrome (AIDS), but also in patients with autoimmune systemic disease, hematological or solid malignancies, transplant recipients or tumors, among others. There exists data that support the idea of which the colonization by P. jirovecii constitutes a risk for development of PCP in subjects submitted to some type of immunosuppression. Tumor necrosis factor alpha (TNF¿) is a pro-inflammatory cytokine that plays a fundamentally role in the control of the Pneumocystis jirovecii infection, for it, It is possible that the effect of the anti-TNF drugs, on having disabled the action of this cytokine, could favor the colonization by P. jirovecii or as PcP's later development in the patients who receive this type of treatments. It could be interesting to know P. jirovecii colonization state in order to know whose patients could receive effective chemoprophylaxis as in tuberculosis infection. Nowadays there is not sufficient information about the frequency of P. jirovecii colonization in patient in treatment with anti-TNF drugs. Objectives: The aims of our study were to obtain information about the colonization by P. jirovecii among patients with systemic diseases treated with different anti TNF drugs and if there were differences rates of colonization by drug or underlying disease. Likewise to know the epidemiological characteristics and the potential risk factors for colonization by P. jirovecii in these patients. Design: we examined oropharingeal washes collected from 19

Introducción. La información sobre la variabilidad de la atención a los pacientes con insuficiencia cardiaca (IC) y su impacto sobre la evolución de la enfermedad en España es escasa. Además, la mayoría de los datos disponibles provienen de ensayos clínicos y estudios realizados en poblaciones muy seleccionadas (varones jóvenes con mayor disfunción ventricular) y menor comorbilidad que la población general. Se pretende conocer si en nuestro entorno existen diferencias en el manejo diagnóstico y terapéutico de los pacientes hospitalizados por IC y analizar su posible impacto en los desenlaces de la asistencia. Objetivo general Conocer la variabilidad clínica y en el manejo diagnósticoterapéutico de los pacientes hospitalizados por un primer episodio de IC y su impacto en la tasa de reingresos y mortalidad durante el primer año de seguimiento, analizando su posible relación con variables del paciente (sexo y edad) y con el área de ingreso (Medicina Interna, Cardiología, Unidad de Estancias Cortas [UEC]).

Objetivos. El objetivo general del presente estudio fue evaluar el posible efecto de Pneumocystis jirovecii sobre la fisiopatología de la EPOC, a través de la respuesta inmune que induce a nivel local y sistémico en estos pacientes con EPOC. Sus objetivos específicos fueron: determinar en nuestro medio la prevalencia de colonización por P. jirovecii y la tasa de exposición al patógeno en pacientes con EPOC; conocer la prevalencia de colonización en los diferentes estadios de la EPOC y evaluar la posible relación entre la colonización y la gravedad de la obstrucción espirométrica; conocer la distribución de genotipos del patógeno en los pacientes con EPOC y la prevalencia de pacientes infectados con mutaciones asociadas a la resistencia al cotrimoxazol; identificar los cambios específicos que la colonización por P. jirovecii pudiera condicionar en la respuesta inmunitaria local y sistémica en los pacientes con EPOC. Métodos: Se ha realizado un estudio transversal en el que se incluyeron 58 pacientes con EPOC en situación clínica estable atendidos en el Servicio de Medicina Interna del Hospital Universitario Vírgen del Rocío. En una segunda fase se diseñó un estudio de casos y controles que incluía como casos a 42 pacientes con EPOC estable colonizados por P jirovecii y como controles a 84 pacientes con EPOC no colonizados; estos sujetos fueron pareados por edad, sexo, hábito tabáquico y estadiaje de la EPOC. De todos los participantes se obtuvo el consentimiento informado por escrito. Se realizó una valoración clínico-epidemiológica estandarizada, que incluyó analítica básica, radiografía de tórax y pruebas funcionales respiratorias; se obtuvieron muestras de esputo para cultivo microbiológico y para la detección Pneumocystis y muestras de suero. Determinaciones moleculares: a) identificación de la colonización por P. jirovecii en muestras de ADN aislado de esputo de los pacientes con EPOC mediante PCR nested en el gen mtLSUrRNA (utilizando los cebadores pAZ102-E/–H

EPIDEMIOLOGÍA DE LA COLONIZACIÓN POR PNEUMOCYSTIS EN POBLACIÓN GENERAL Directores: Francisco Javier Medrano Ortega, Enrique Calderón Sandubete Tutor: Eduardo Lissen Otero Doctorando: Rosa María Yang Lai Antecedentes: El conocimiento sobre la epidemiología de la infección humana por Pneumocystis jirovecii es aún muy limitado, y no están bien establecidos cuales son sus reservorios y fuentes de transmisión. En estudios preliminares se ha demostrado la presencia del patógeno en el árbol respiratorio de sujetos adultos sanos inmunocompetentes. Sin embargo, en el momento actual la magnitud y relevancia de este fenómeno es desconocida. Objetivo: El objetivo general del presente estudio fue conocer las características epidemiológicas de la colonización por Pneumocystis en la población general. Sus objetivos específicos fueron: determinar la prevalencia de colonización por Pneumocystis en la población general de un área del sur de España; investigar posibles factores asociados a una mayor tasa de colonización por el patógeno; estudiar la distribución de genotipos del patógeno en la población general y la prevalencia de sujetos colonizados con mutaciones asociadas a la resistencia al cotrimoxazol. Métodos: Se realizó un estudio transversal de prevalencia de base poblacional. La población estudiada fue el municipio de El Coronil. El tamaño muestral se realizó mediante un muestreo sistemático con arranque aleatorio. Tras consentimiento informado por escrito de los participantes se realizó una valoración clínico-epidemiológica estandarizada, que incluyó analítica básica y perfil inmunológico, y se obtuvieron muestras de lavado orofaríngeo para la detección de dos loci independientes del genoma de P. jirovecii: el gen de la subunidad mayor del ribosoma mitocondrial (mtLSU rRNA), mediante PCR anidada y el gen que codifica la síntesis de la enzima dihidropteroato sintetasa (DHPS), mediante PCR ¿touchdown¿. La colonización se definió como detección de ADN de P. jirovecii en el árbo

We report a case of Pneumocystis jirovecii transmission from colonized grandparents to their infant granddaughter. Genotyping of P. jirovecii showed the same genotypes in samples from the infant and her grandparents. These fi ndings support P. jirovecii transmission from immunocompetent carrier adults to a susceptible child.