Genetic characterization of the mechanisms of resistance to amoxicillin/clavulanate and third-generation cephalosporins in Salmonella enterica from three Spanish hospitals

The mechanisms of antimicrobial resistance were characterized in 90 Salmonella enterica isolates either resistant or with intermediate resistance to amoxicillin/clavulanate (AMCR/I) or resistant to third-generation cephalosporins (C3GR). These isolates were recovered in three Spanish hospitals during 2007-2009. The C3GR phenotype was expressed by three isolates that carried the following extended-spectrum β-lactamase genes: phage-associated blaCTX M-10 in S. Virchow, blaCTX-M-14a surrounded by ISEcp1 and IS903 in S. Enteritidis, and blaCTX-M-15 linked to ISEcp1 and orf477 in S. Gnesta (first description in this serotype). The AMCR/I phenotype was found in 87 isolates (79 S. Typhimurim, 7 S. Enteritidis, and one S. Thompson). The blaPSE-1 gene, followed by blaOXA-1 was mostly found among S. Typhimurim, and the blaTEM-1 gene among S. Enteritidis. Three different gene combinations [blaPSE-1+floR+aadA2+sul+tet(G); blaOXA-1+catA+aadA1/strA-strB+sul+tet(B) and blaTEM-1+cmlA1+aadA/strA-strB+sul+tet(A)/tet(B) genes] were associated with the ampicillin-chloramphenicol-streptomycin-sulfonamides-tetracycline phenotype in 68 AMCR/I S. enterica isolates. Class 1 integrons were observed in 79% of the isolates and in most of them (45 isolates) two integrons including the aadA2 and blaPSE-1 gene cassettes, respectively, were detected. The blaOXA-1+aadA1 arrangement was detected in 23 isolates, and the aac(6′)-Ib-cr+blaOXA-1+catB3+arr3 in another one. Non-classicclass 1 integrons were found in three isolates: dfrA12+orfF+aadA2+cmlA1+aadA1 (1 isolate), dfrA12+orfF+aadA2+cmlA1+aadA1+qacH+IS440+sul3 (1 isolate) and dfrA12+orfF+aadA2+cmlA1+aadA1+qacH+IS440+ sul3+orf1+mef(B)Δ-IS26 (1 isolate). Taken together, these results underline the need for clinical concern regarding β-lactam resistance in Salmonella and thus for vigilant monitoring

Whole-exome sequencing reveals ZNF408 as a new gene associated with autosomal recessive retinitis pigmentosa with vitreal alterations

Retinitis pigmentosa (RP) is a group of progressive inherited retinal dystrophies that cause visual impairment as a result of photoreceptor cell death. RP is heterogeneous, both clinically and genetically making difficult to establish precise genotype–phenotype correlations. In a Spanish family with autosomal recessive RP (arRP), homozygosity mapping and whole-exome sequencing led to the identification of a homozygous mutation (c.358_359delGT; p.Ala122Leufs*2) in the ZNF408 gene. A screening performed in 217 additional unrelated families revealed another homozygous mutation (c.1621C>T; p.Arg541Cys) in an isolated RP case. ZNF408 encodes a transcription factor that harbors 10 predicted C2H2-type fingers thought to be implicated in DNA binding. To elucidate the ZNF408 role in the retina and the pathogenesis of these mutations we have performed different functional studies. By immunohistochemical analysis in healthy human retina, we identified that ZNF408 is expressed in both cone and rod photoreceptors, in a specific type of amacrine and ganglion cells, and in retinal blood vessels. ZNF408 revealed a cytoplasmic localization and a nuclear distribution in areas corresponding with the euchromatin fraction. Immunolocalization studies showed a partial mislocalization of the p.Arg541Cys mutant protein retaining part of the WT protein in the cytoplasm. Our study demonstrates that ZNF408, previously associated with Familial Exudative Vitreoretinopathy (FEVR), is a new gene causing arRP with vitreous condensations supporting the evidence that this protein plays additional functions into the human retina.This work is supported by CIBERER (06/07/0036), FIS (PI013/00226), Ministry of Economy and Competitiveness-FEDER (BFU2012-36845), RETICS (RD12/0034/0010), Fundación ONCE, Fundaluce and grants BIO2011-27069 from the Spanish Ministry of Economy and Competitiveness, and PROMETEOII/2014/025 from the Conselleria de Educacio of the Valencia Community. PC is supported by Fundación Conchita Rábago (FCR), MC by Miguel Servet ISCIII (CP/03256) and dS by CAPES Foundation, Ministry of Education of Brazil

Epidemiología y características del ictus isquémico en el adulto joven en Aragón

Introducción Alrededor de 15 millones de personas sufren un ictus cada año, de los que un 10-15% ocurre en menores de 50 años (ictus en el adulto joven). La prevalencia de los distintos factores de riesgo vascular y las estrategias sanitarias para el manejo del ictus varían a nivel mundial, siendo interesante conocer la epidemiología y las características específicas de cada región. El objetivo de este estudio fue determinar la prevalencia de los diferentes factores de riesgo vascular, la etiología y las características de los ictus isquémicos en el adulto joven en la comunidad autónoma de Aragón. Métodos Estudio multicéntrico, de corte transversal, realizado por los Servicios de Neurología de todos los hospitales del Servicio Aragonés de Salud (SALUD). Se identificó a todos los pacientes entre 18 y 50 años que ingresaron en cualquiera de estos hospitales con el diagnóstico de ictus isquémico o AIT entre enero del 2005 y diciembre del 2015. Se recogieron variables demográficas, factores de riesgo vascular y tipo de ictus isquémico entre otras. Resultados En el periodo de estudio, 786 pacientes entre 18 y 50 años ingresaron con el diagnóstico de ictus isquémico o AIT en algún hospital del SALUD, con una tasa anual promedio de 12, 3 por 100.000 habitantes. La mediana de su edad fue de 45 años (RIQ: 40-48 años). El factor de riesgo vascular más prevalente fue el tabaquismo, 404 (51, 4%). La mayoría fue de causa indeterminada (36, 2%), seguida por «otras causas» (26, 5%). La mediana de puntuación en la escala NIHSS fue de 3, 5 (RIQ: 2, 07, 0). En total, 211 (26, 8%) de los ingresos fueron por AIT. De los pacientes que ingresaron con el diagnóstico de ictus isquémico, 59 (10, 3%) se fibrinolizaron. Conclusiones El ictus isquémico en el adulto joven no es infrecuente en Aragón y en un importante número de casos es de etiología indeterminada, por lo que es necesario implementar medidas que nos permitan mejorar su estudio, disminuir su incidencia y prevenir su recurrencia. Introduction: Stroke affects around 15 million people per year, with 10%-15% occurring in individuals under 50 years old (stroke in young adults). The prevalence of different vascular risk factors and healthcare strategies for stroke management vary worldwide, making the epidemiology and specific characteristics of stroke in each region an important area of research. This study aimed to determine the prevalence of different vascular risk factors and the aetiology and characteristics of ischaemic stroke in young adults in the autonomous community of Aragon, Spain. Methods: A cross-sectional, multi-centre study was conducted by the neurology departments of all hospitals in the Aragonese Health Service. We identified all patients aged between 18 and 50 years who were admitted to any of these hospitals with a diagnosis of ischaemic stroke or TIA between January 2005 and December 2015. Data were collected on demographic variables, vascular risk factors, and type of stroke, among other variables. Results: During the study period, 786 patients between 18 and 50 years old were admitted with a diagnosis of ischaemic stroke or TIA to any hospital of Aragon, at a mean annual rate of 12.3 per 100 000 population. The median age was 45 years (IQR: 40-48 years). The most prevalent vascular risk factor was tobacco use, in 404 patients (51.4%). The majority of strokes were of undetermined cause (36.2%), followed by other causes (26.5%). The median NIHSS score was 3.5 (IQR: 2.0-7.0). In total, 211 patients (26.8%) presented TIA. Fifty-nine per cent of the patients admitted with a diagnosis of ischaemic stroke (10.3%) were treated with fibrinolysis. Conclusions: Ischaemic stroke in young adults is not uncommon in Aragon, and is of undetermined aetiology in a considerable number of cases; it is therefore necessary to implement measures to improve study of the condition, to reduce its incidence, and to prevent its recurrence

Programa de Atención al Ictus en Aragón (PAIA). Estrategia del cambio y resultados en el periodo 2009-2014

Introducción En 2008, Aragón tenía tasas de morbimortalidad y discapacidad por ictus superiores a las del conjunto de España. Se estableció la necesidad de desarrollar un Programa de Atención al Ictus (PAIA). Material y métodos Damos a conocer la dinámica de planificación, implantación, evaluación y mejora que se ha desarrollado entre los años 2009-2014 y sus resultados a 5 años. Resultados Se ha mejorado en la estructura, en los procesos y en los resultados, con mejoría en los indicadores clave de la asistencia (audit 2008-2010-2012) y otros: tasa ictus 2013: 2, 07 (2008: 2, 36); 78% ictus atendidos en áreas/unidades en 2014 (30%, 2008); tasa fibrinólisis 8, 3% en 2014 (4, 4%, 2010); fibrinólisis hospitales secundarios (30% total); fibrinólisis con teleictus 9%; descenso de la mortalidad por ictus, 38%; años de vida prematura perdidos 67, 7 (2013)/144 (2008); capacitación de enfermería, desarrollo de la neurosonología, trabajo en red, con protocolos y buenas prácticas compartidos entre sectores sanitarios, etc. Conclusiones La gestión por procesos y equipos multidisciplinares desplegados en una distribución territorial integral, con protocolos y referencias establecidas y una dinámica de evaluación y mejora continua, ha demostrado ser una herramienta potente para garantizar la calidad y la equidad. El PAIA, por su dinámica de mejora sostenida y la implicación de los clínicos, es un buen ejemplo de gestión clínica y trabajo en red. Introduction: In 2008, stroke mortality, morbidity, and disability rates in Aragon were higher than the average in Spain. These data underscored the need to develop a stroke care programme (PAIA). Material and methods: We present the dynamics of planning, implementation, evaluation, and improvement developed between 2009 and 2014 as well as the results of the PAIA after that 5-year period. Results: Structure, processes, and outcomes have improved with reference to the key indicators of healthcare (audit: 2008, 2010, 2012) among others: stroke rate in 2013 was 2.07 (2.36 in 2008); 78% of strokes were managed in stroke units in 2014 (30% in 2008); rate of fibrinolysis was 8.3% in 2014 (4.4% in 2010); fibrinolysis was administered in secondary hospitals (30% of the total); fibrinolysis was administered by Telestroke in 9%; stroke mortality decreased (38%); 67.7 years of potential life lost (YPLL) in 2013 (144 in 2008); nurse training; development of neurosonology; networking; sharing protocols and best practices between health sectors, etc. Conclusions: Integrated process management and multidisciplinary teams distributed and deployed over an entire territory with established protocols, references, evaluations, and continuous development, have been proven powerful tools to ensure both quality and equality. The PAIA is a good example of clinical governance and networking due to its dynamic and sustained improvement and cooperation between clinicians