Análisis de la mortalidad y factores pronósticos en una cohorte de pacientes con Lupus Eritematoso Sistémico seguidos en una unidad especializada de Medicina Interna

Introducción: El lupus eritematoso sistémico (LES) es una enfermedad autoinmune sistémica que desde las primeras descripciones de la enfermedad se ha asociado a una elevada mortalidad. Con los avances diagnóstico-terapéuticos su pronóstico ha mejorado, pero, no obstante, existe una elevada variabilidad en los datos publicados, posiblemente en relación con el país de origen, etnia o características basales de los pacientes estudiados. Objetivo: Describir las características clínicas y demográficas de los pacientes en una extensa cohorte de pacientes con LES, y analizar la supervivencia, exceso de mortalidad y causas de muerte en nuestro medio. Métodos: Estudio observacional retrospectivo de pacientes diagnosticados con LES y seguidos en la una unidad específica de Medicina Interna desde 1981 a 2015. Se recabó la información de registro hospitalario y de la historia clínica de los pacientes, y se confirmó el estado vital de los pacientes perdidos de seguimiento por medio de registros autonómicos y nacionales de defunción. Para valorar el impacto de la enfermedad en la supervivencia se usaron la razón estandarizada de mortalidad (RME) y los años de vida potenciales perdidos (AVPP), usando como referencia los datos de la población general nacional y regional. Resultados: Se han analizado a 807 pacientes, lo que supuso 14.618 personas-año, siendo el 11,8% hombres y habiendo presentado un inicio tardío el 12,4% de los pacientes. Las manifestaciones clínicas más frecuentes fueron las cutáneas, articulares y hematológicas; y se encontraron diferencias significativas en la expresión clínica de los pacientes según el sexo y la edad de inicio de la enfermedad. Se observó una incidencia mayor de eventos coronarios y neoplasias hematológicas comparado con la población general. La supervivencia global de la cohorte fue de 96,2% a los 5 años, 93% a los 10 años y 88,5% a los 15 años. En los pacientes con lupus de inicio tardío, pediátrico y hombres la supervivencia a los 10 años fue de 73%, 95,8% y 88,7% respectivamente. Los pacientes con afectación renal presentaron una supervivencia del 90,2% a los 10 años, habiendo mejorado de forma significativa en los últimos años. Durante el seguimiento se produjeron 168 defunciones, pudiéndose establecer la causa en el 89,3% de los casos, siendo las principales las de causa vascular (28%), enfermedades infecciosas (18,5%) y LES (16,1%). La mortalidad de la cohorte fue 3,2 (IC95 2,8-3,8) veces superior al de la población general, siendo mayor en las mujeres, pacientes jóvenes, al inicio de la enfermedad y en aquellos con nefritis lúpica. Se observó un exceso de mortalidad por causas infecciosas de 12,7 veces el de la población general, y una RME algo menor de 3 para las muertes por causa digestivas o vasculares. De estas últimas muestra una RME particularmente elevadas (por encima de 10 veces la población general) la patología arterial diferente a coronaria y cerebrovascular (aneurismas de aorta, trombosis arteriales, hipertensión arterial pulmonar o isquemia mesentérica). Las causas de muerte que más impacto tuvieron en el AVPP fueron la hipertensión arterial pulmonar, las infecciones y el LES con más de 30 AVPP de media. En el estudio multivariante se comportaron como factores de mal pronóstico la nefritis, la miocardiopatía, la anemia hemolítica, la hipertensión arterial pulmonar, la edad de inicio y el sexo masculino, y como factor protector el lupus discoide. Conclusiones: El sexo y la edad de inicio determinaron diferentes patrones de enfermedad que tuvieron implicaciones en el pronóstico. No obstante, la supervivencia global se mostró por encima del 90% a los 10 años. Comparando estos datos con la población general la mortalidad en los pacientes con LES fue 3,2 veces superior, siendo este exceso particularmente elevado en aquellos de edades tempranas de la vida o con afectación renal. Aunque la primera causa de muerte fue la vascular, la actividad lúpica y las enfermedades infecciosas fueron las que mostraron un mayor impacto al provocar muertes más prematuras en un elevado número

Prevalence of Pneumocystosis in Sub-Saharan Africa and Helminth Immune Modulation

Sub-Saharan Africa is the region of the world with the highest prevalence of helminth infections. To protect themselves from the defensive mechanisms of their respective hosts, helminths modulate their immune responses. This modulation has relevant clinical and epidemiological consequences, including the inhibition of inflammatory processes that characterize infection by other microorganisms. Severe Pneumocystis pneumonia is characterized by an intense inflammatory reaction that can lead to death. Acquired immunodeficiency syndrome is the main predisposing factor to the development of pneumocystosis. Although the introduction of highly active antiretroviral therapy has led to a notable decline in the incidence of acquired immunodeficiency syndrome-associated complications, pneumocystosis continues to be an important global health problem. Despite the high incidence of human immunodeficiency virus infection in the sub-Saharan region, the prevalence of Pneumocystis pneumonia there has been lower than expected. Several factors, or combinations thereof, may contribute to this evolution. Here, we hypothesize the possible role of helminth immune modulation as an important issue at play. On the other hand, and looking ahead, we believe that the immune modulation achieved by helminths may be an important factor to consider during the design and evaluation processes of vaccines against Pneumocystis jirovecii to be used in Sub-Saharan Africa. The requirements of a balanced triggering of different types of immune responses for controlling the infection produced by this microorganism, as observed during experiments in animal models, support this final consideration.Institute of Health Carlos III, Spanish Ministry of Science, Innovation and University FIS-PI19/0184

Multilocus Genotyping of Pneumocystis jirovecii from Deceased Cuban AIDS Patients Using Formalin-Fixed and Paraffin-Embedded Tissues

The results of the genotypic characterization of Pneumocystis jirovecii are described in lung tissue samples from 41 Cubans who died of AIDS with pneumocystosis between 1995 and 2008. Histological sections of the lung preserved as formalin-fixed and paraffin-embedded tissue were examined. PCR amplification and nucleotide sequencing of the two mitochondrial genes (large and small) of the pathogen allowed verification of a predominance of genotype 3 (85T/248C) of the large mitochondrial gene and genotype 3 (160A/196T) of the small mitochondrial gene over a period of 14 years (1995–2008). These results suggest that the 85T/248C//160A/196T genotype circulates with the highest frequency (81.3%) among AIDS patients in Cuba. Multilocus analysis indicates a limited circulation of pathogen genotypes on the island with the existence of a clonal genotype with an epidemic structure. Furthermore, it appears that circulating strains of P. jirovecii have not developed mutations related to sulfonamide resistance. Taken together, the data in this study revealed important elements about pneumocystosis in Cuban patients dying of AIDS and the usefulness of formalin-fixed and paraffin-embedded samples to carry out molecular epidemiology studies of P. jirovecii

GBA Variants Influence Motor and Non-Motor Features of Parkinson’s Disease.

The presence of mutations in glucocerebrosidase (GBA) gene is a known factor increasing the risk of developing Parkinson’s disease (PD). Mutations carriers have earlier disease onset and are more likely to develop neuropsychiatric symptoms than other sporadic PD cases. These symptoms have primarily been observed in Parkinson’s patients carrying the most common pathogenic mutations L444P and N370S. However, recent findings suggest that other variants across the gene may have a different impact on the phenotype as well as on the disease progression. We aimed to explore the influence of variants across GBA gene on the clinical features and treatment related complications in PD. In this study, we screened the GBA gene in a cohort of 532 well-characterised PD patients and 542 controls from southern Spain. The potential pathogeniticy of the identified variants was assessed using in-silico analysis and subsequently classified as benign or deleterious. As a result, we observed a higher frequency of GBA variants in PD patients (12.2% vs. 7.9% in controls, p = 0.021), earlier mean age at disease onset in GBA variant carriers (50.6 vs. 56.6 years; p = 0.013), as well as more prevalent motor and non-motor symptoms in patients carrying dele- terious variants. In addition, we found that dopaminergic motor complications are influenced by both benign and deleterious variants. Our results highlight the fact that the impact on the phenotype highly depends on the potential pathogenicity of the carried variants. Therefore, the course of motor and non-motor symptoms as well as treatment-related motor complica- tions could be influenced by GBA variants.Ministerio de Economı́a y Competitividad SAF2007-60700.Instituto de Salud Carlos III PI10/01674, PI13/01461, PI14/01823.Consejerı́a de Economı́a, Innovación, Ciencia y Empleo CVI-02526, CTS- 7685Consejería de Igualdad, Salud y Políticas Sociales PI-0377/2007, PI-0741/2010, PI-0437-2012, PI-0471-201

Pneumocystis jirovecii Transmission from Immunocompetent Carriers to Infant

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 findings support P. jirovecii transmission from immunocompetent carrier adults to a susceptible child

Role of biological and non biological factors in congestive heart failure mortality: PREDICE-SCORE: A clinical prediction rule

Background: Congestive 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 project was to develop a clinical prediction model of biological and non biological factors in patients with first diagnosis of HF that facilitates the risk-stratification and decision-making process at the point of care. Methods and Results: Historical cohort analysis of 600 patients attended at three tertiary hospitals and diagnosed of a first episode of HF according Framingham criteria. There were followed 1 year. We analyzed sociodemographic, clinical and laboratory data with potential prognostic value. The modelling process concluded into a logistic regression multivariable analysis and a predictive rule: PREDICE SCORE. Age, dependency for daily basic activities, creatinine clearance, sodium levels at admission and systolic dysfunction diagnosis (HF with left ventricular ejection fraction < 40%) were the selected variables. The model showed a c-statistic of 0.763. PREDICE Score, has range of 22 points to stratifications of 1-year mortality. Conclusions: The follow-up of 600 patients hospitalized by a first episode of congestive HF, allowed us to obtain a predictive 1 year mortality model from the combination of demographic data, routine biochemistry and easy handling social and functional variables at the point of care. The variables included were non-invasive, undemanding to collect, and widely available. It allows for risk stratification and therapeutical targeting and may help in the clinical decisions process in a sustainable way

Pneumocystis jirovecii in General Population

P. jirovecii colonization can be frequently detected in immunocompetent adults, which suggests that the general population could be a source of this infection

Parasites and malignancies, a review, with emphasis on digestive cancer induced by Cryptosporidium parvum (Alveolata: Apicomplexa)

The International Agency for Research on Cancer (IARC) identifies ten infectious agents (viruses, bacteria, parasites) able to induce cancer disease in humans. Among parasites, a carcinogenic role is currently recognized to the digenetic trematodes Schistosoma haematobium, leading to bladder cancer, and to Clonorchis sinensis or Opisthorchis viverrini, which cause cholangiocarcinoma. Furthermore, several reports suspected the potential association of other parasitic infections (due to Protozoan or Metazoan parasites) with the development of neoplastic changes in the host tissues. The present work shortly reviewed available data on the involvement of parasites in neoplastic processes in humans or animals, and especially focused on the carcinogenic power of Cryptosporidium parvum infection. On the whole, infection seems to play a crucial role in the etiology of cancer.Le Centre International de Recherche sur le Cancer (CIRC) recense dix agents infectieux (virus, bactéries, parasites) responsables de pathologies cancéreuses chez l’homme. Parmi les parasites actuellement reconnus comme cancérogènes figurent les trématodes digénétiques Schistosoma haematobium, agent de cancer vésical, Clonorchis sinensis et Opisthorchis viverrini, agents de cholangiocarcinome. Par ailleurs, plusieurs rapports suspectent l’association potentielle entre d’autres infections parasitaires (à protistes ou à métazoaires) et le développement de changements néoplasiques dans les tissues de l’hôte. Cette revue propose une vue d’ensemble des données disponibles sur les relations entre parasites et processus néoplasiques chez l’homme et autres animaux. À la lumière de découvertes récentes, le cas de Cryptosporidium parvum fait l’objet d’une analyse plus approfondie. Globalement, les infections semblent jouer un rôle crucial dans l’étiologie du cance

Hepatitis crónicas virales B y C en población inmigrante en España

Background: the prevalence of chronic viral hepatitis in Spain could vary because of the immigrants coming from countries having an elevated with a higher endemicity of hepatitis B and C virus. Hepatitis B and hepatitis C virus infections are an important health problem worldwide taking into account their chronic consequences. The aim of this study was to know the impact of immigration in the prevalence of chronic viral hepatitis in Spain. Methods: qualitative of scientific papers searching in Medline and MEDES-MEDicina, with date limit January 1998- December 2012 and only papers in English and Spanish. Results: data from 19 original articles were analyzed. The prevalences of hepatitis B and C virus infections in the immigrant population, on the whole, are higher than Spanish population. Immigrants from Africa and East European countries presented the higher prevalence of Hepatitis B and Hepatitis C virus infection, whereas the Latin American-origin population displayed the lowest one. Conclusion: the prevalences of hepatitis B and C virus infections in the immigrant population suggest they could have a substantial public health impact in Spain.Fundamentos: En España la prevalencia de la hepatitis crónicas de origen viral puede variar a causa de los inmigrantes procedentes de áreas de elevada prevalencia de infección por virus B y C de la hepatitis. La infección por estos virus es un problema importante de salud pública global por los procesos crónicos que originan. El objetivo del estudio fue conocer el impacto de la inmigración en la prevalencia de las hepatitis crónicas virales en España. Métodos: Revisión bibliográfica cualitativa de la literatura científica sobre el tema publicada entre enero de 1998 y diciembre de 2012 utilizando las bases Medline y MEDES-MEDicina. Resultados: Se analizaron los datos procedentes de 19 artículos originales. En conjunto la prevalencia de infección por los virus B y C de la hepatitis fue mayor en la población emigrante que la descrita para la población general española. Los emigrantes de África y Europa del Este presentaron las mayores prevalencias y los inmigrantes iberoamericanos las menores. Conclusiones: La prevalencia de las infecciones por virus B y C de la hepatitis en inmigrantes sugiere que podrían tener un importante impacto en la salud pública en España