In vivo Neutralization of Pro-inflammatory Cytokines During Secondary Streptococcus pneumoniae Infection Post Influenza A Virus Infection

An overt pro-inflammatory immune response is a key factor contributing to lethal pneumococcal infection in an influenza pre-infected host and represents a potential target for therapeutic intervention. However, there is a paucity of knowledge about the level of contribution of individual cytokines. Based on the predictions of our previous mathematical modeling approach, the potential benefit of IFN-γ- and/or IL-6-specific antibody-mediated cytokine neutralization was explored in C57BL/6 mice infected with the influenza A/PR/8/34 strain, which were subsequently infected with the Streptococcus pneumoniae strain TIGR4 on day 7 post influenza. While single IL-6 neutralization had no effect on respiratory bacterial clearance, single IFN-γ neutralization enhanced local bacterial clearance in the lungs. Concomitant neutralization of IFN-γ and IL-6 significantly reduced the degree of pneumonia as well as bacteremia compared to the control group, indicating a positive effect for the host during secondary bacterial infection. The results of our model-driven experimental study reveal that the predicted therapeutic value of IFN-γ and IL-6 neutralization in secondary pneumococcal infection following influenza infection is tightly dependent on the experimental protocol while at the same time paving the way toward the development of effective immune therapies

Cambios Anatómicos y Funcionales en Pacientes con Enfermedades Paquicoroideas tras Tratamiento con Terapia Fotodinámica.

Objetivo: Analizar la respuesta anatómica y funcional tras uno y tres meses después de la terapia fotodinámica (TFD) en pacientes con enfermedades paquicoroideas mediante mejor agudeza visual corregida, microperimetría de evaluación de integridad macular (MAIA) y tomografía de coherencia óptica de fuente de barrido (SS-OCT).Métodos: Estudio prospectivo durante tres meses de 11 pacientes con enfermedades paquicoroideas tratados con TFD de media fluencia (25 J/cm2) y dosis completa (6 mg/m2) de duración estándar (83 segundos) tras el diagnóstico mediante angiografía con fluoresceína (AF) y angiografía con verde de indocianina (AVI). Se evaluaron 22 ojos (11 casos y 11 controles) antes, un mes y tres meses después de la TFD con SS-OCT, midiendo el grosor de la retina (membrana Limitante Interna-EPR) y el grosor de la coroides (EPR-capa externa coroidea) además de la sensibilidad retiniana, medida por MAIA y mejor agudeza visual corregida (MAVC).Resultados: El espectro paquicoroideo fue diagnosticado por AF y AVI en ocho pacientes con coriorretinopatía serosa central, uno con neovasculopatía paquicoroidea y dos con vasculopatía coroidea polipoidea. Antes de la TFD los casos mostraron una menor sensibilidad retiniana en las 14 regiones analizadas por MAIA en comparación con el grupo control (p 0.05), manteniéndose la mejoría a los 3 meses (p > 0.05). A nivel anatómico, tras un mes de tratamiento, se encontró una disminución en el grosor de la retina y coroides por SS-OCT (p> 0.05), siendo significativamente estadístico a los 3 meses con una disminución del grosor coroideo en los cuadrantes internos incluyendo el grosor coroideo subfoveal (SFCT, supero- interno, temporal-interno, nasal-interno p 0,05) en los cuadrantes coroideos tras TFD al mes y a los tres meses.Conclusión: La TFD indujo una mejoría funcional precoz de los parámetros de AV y sensibilidad retiniana foveal tras un mes de tratamiento, así como una reducción en el grosor interno de la coroides medido mediante SS-OCT de forma mas tardía, a los 3 meses de la TFD.<br /

Arte paleolítico en Salamanca. Nuevos hallazgos en el yacimiento de El Paraje de La Salud

This paper presents a study of the newly discovered panel with Palaeolithic engravings at El Paraje de La Salud (Salamanca). We use three-dimensional restitution techniques in order to document both the support and the recorded motifs. It is one more example of open-air Premagdalenian art. Their technical and formal characteristics are similar to those of representations at the Portuguese sites of Fariseu and Penascosa in the Côa, as well as those at the recently discovered Foz do Río Tua.En este trabajo se presentan los resultados de la intervención realizada en el yacimiento de El Paraje de La Salud (Salamanca), con motivo del descubrimiento de un nuevo panel con grabados de cronología paleolítica. El conjunto ha sido estudiado empleando técnicas de restitución tridimensional con el fin de documentar tanto el soporte como los motivos grabados. Se trata de una muestra más de arte con cronología premagdaleniense realizado al aire libre, cuyas características técnicas y formales permiten ponerlo en relación con representaciones aparecidas en los conjuntos portugueses de Fariseu y Penascosa en el Côa, así como con el recientemente descubierto en Foz do Río Tua

New Landmarks, Signs, and Findings in Optical Coherence Tomography

Spectral domain optical coherence tomography (SD-OCT) is a common useful noninvasive imaging instrument which is used for the diagnosis and follow-up of macular disorders. The clinical findings by OCT in these pathologies are well known. Currently, due to the development of this technology and its wide use, new OCT findings have been reported in the literature. The aim of this chapter is to describe new pathological or abnormal signs and findings in SD-OCT, including hyperreflective spots or dots, flyer saucer sign, outer retinal tubulations, dipping sign, focal choroidal excavation, outer retina-choroid complex splitting, foveal pseudocyst, brush border pattern, dome-shaped macula, pearl necklace sign, choroidal macrovessel, cystoid foveal degeneration, and disorganization of the retinal inner layers (DRIL)

Efficacy of the tissue regenerating agent (RGTA) in the treatment of neurotrophic corneal ulcers and persistent epithelial defects

Purpose : To report the results obtained in a series of 58 eyes with chronic corneal ulcers and persistent epithelial defects resistant to conventional therapy and treated with 0.01% poly-carboxymethylglucose sulfate (RGTA, Cacicol®). Methods : A prospective study was made of 58 eyes of patients with corneal ulcers and persistent epithelial lesions secondary to neurotrophic disorders, caustic damage, ulcerated metaherpetic lesions, Stevens-Johnson syndrome, peripheral ulcerative keratitis and severe dry eye, among other conditions. The ulcers were essentially chronic and slow-evolving, with mean vertical and horizontal diameters of 2.4 and 2.7 mm, respectively (range 1-5.5 mm). All patients had been previously treated with classical tear substitutes, and some had also received blood products, topical cyclosporine, corticosteroids, amniotic membrane coverings, therapeutic contact lenses and/or a vitamin-based eye ointment. The patients received an initial dose of one drop in the morning every 48 hours during 10 days. After evaluation of the effects of treatment, new dosing schemes were prescribed for those patients who had improved their clinical condition though without complete resolution of the disease. Results : Important variation was observed in the time to recovery of corneal integrity, ranging from a few days to some weeks, depending on the severity and etiology of the case. Full healing was recorded in 50 patients. The patients with large neurotrophic ulcers showed improvement of the lesions, with a decrease in lesion size after 15 days of treatment. Eight eyes did not achieve complete healing. In the case of severe ulceration and when a positive effect was observed after one month, treatment was continued with spacing of the applications until complete healing was achieved. All patients reported subjective improvement. The drug showed immediate efficacy in 11 eyes with epithelialisation disorders following PRK or trauma, with recovery of tissue integrity after the first treatment period. Conclusions : The tissue regenerating agent (RGTA, Cacicol®) is an interesting and effective topical adjuvant product for the treatment of severe and chronic corneal ulcers resistant to conventional treatment. Its efficacy remains to be confirmed in the context of double-blind, randomised clinical trials

New correlations between ocular parameters and disease severity in Spanish patients with Gaucher’s disease Type I

Background: Gaucher’s disease is associated with a high variety of structural and functional abnormalities in the eye, which do not always affect visual acuity. The purpose of this study was to analyse ocular features in Spanish patients with Gaucher’s disease type I, and to investigate their possible correlation with phenotypic and burden parameters of this entity. Methods: This cross-sectional observational study compared parameters belonging to 18 eyes from 9 Spanish patients with Gaucher’s disease Type I with 80 eyes from 40 healthy controls. Complete ophthalmological examination included choroidal and retinal thickness maps with swept source optical coherence tomography. Systemic analysis included genotype, plasmatic biomarkers, [ferritin, chemokine ligand 18 (CCL18) and chitotriosidase (ChT)] and severity scoring systems results [“Gaucher Disease Severity Score Index Type I" (GauSSI-I) and “Gaucher disease severity scoring system” (GD-DS3)]. Results: Nine subjects (18 eyes) were cases (female: 55.5%, mean age 45 years; male: 44.5%, mean age 36 years) and 40 subjects (80 eyes) were controls (female: 49%, mean age 50 years; male: 51%, mean age 55 years). There were no statistically significant differences when comparing ocular parameters (visual acuity; axial length, refractive errors, corneal parameters, lens, retinal and choroidal thickness) between case and control subjects (p&gt;0.05). A statistically significant moderate correlation was observed between lower retinal thickness and choroidal quadrants thickness and greater disease severity scores. A lower central retinal thickness also correlates with higher biological plasmatic levels, and has a statistically significant association with the most affected patient with genotype N370S/Del 55pb. Conversely, higher pachymetry involves a more severe plasmatic concentration of biomarkers. Conclusions: Our results suggest that pachymetry, and retinal and choroidal thickness, are associated with burden biomarkers and disease severity index scores in Spanish patients with Gaucher’s disease Type I

Cost-effectiveness of dexamethasone compared with aflibercept in naïve diabetic macular edema

Abstract Background To assess the cost-effectiveness of the delayed-release device of dexamethasone compared with aflibercept in the treatment of patients with naïve diabetic macular edema (DME) from a societal perspective in the healthcare sector Zaragoza III in Spain. Methods A Markov model with five states defined by visual acuity (VA) in the better-seeing eye (Snellen scale) and an additional death state were constructed. Two cohorts of patients were distributed along the VA states and treated during a year with either dexamethasone or aflibercept. One-year follow-up on each group was performed. Medical costs related to the DME treatment and follow-up, medical costs related to the DME comorbidities, and non-medical-related costs were taken into account. Costs (2020 €), health outcomes (Quality-Adjusted Life Years-QALYs), both discounted at a 3.5% annual rate, and incremental cost-effectiveness ratios (ICER: €/QALY) were determined for a lifetime horizon in the base case analysis. Results Patients treated with dexamethasone were €77,349 more costly and provided 2.667 additional QALYs (€29,002/QALY) than those treated with aflibercept. The variable efficiency per patient was calculated dividing the improvement in quality of life (on the VFQ-25 scale) by the cost of the treatment. With the obtained results it can be concluded that the efficiency of treating the patients with dexamethasone is significantly superior than the efficiency of treating them with aflibercept. Conclusions The cost per QALY gained with the delayed-release device of dexamethasone compared with the one obtained by aflibercept in the naïve DME population is just below the €30,000 threshold, below which, new drugs are sometimes regarded as cost-effective strategies in Spain. In this model, the key variables with greater impact on the cost-effectiveness results were the selected time horizon, the chosen extrapolation method and the number of aflibercept and dexamethasone injections

WIKIPREHISTORIA: Creación de contenidos web para procesos de enseñanza y de aprendizaje de la Prehistoria basados en la herramienta Wikcionario (Wikimedia)

Memoria ID-042 Ayudas de la Universidad de Salamanca para la innovación docente, curso 2020-2021

Resultados visuales en pacientes sometidos a cirugía de desprendimiento de retina regmatógeno

Introducción: El desprendimiento de retina es un causante de pérdida visual frecuente entre la población. En la actualidad, el tratamiento para esta patología es quirúrgico, siendo la vitrectomía pars plana (VPP), la hebilla escleral (HE) o cerclaje y la combinación de ambos (VPP+HE) los más utilizados por los cirujanos. Sin embargo, los resultados visuales y anatómicos, el desarrollo de catarata y las tasas de éxito tras cirugía de retina están en continuo estudio. Objetivos: Evaluar los resultados visuales de pacientes sometidos a cirugía de desprendimiento de retina. Estudiar como influye en los resultados visuales la implicación de la afectación macular en el desprendimiento y el tipo de cirugía realizada (VPP/VPP+HE). Como objetivos secundarios se evaluará el éxito anatómico de la vitrectomía pars plana (VPP) y de esta misma combinada con el cerclaje o hebilla escleral (HE). Métodos: Estudio retrospectivo a 12 meses de seguimiento de 47 pacientes afectos de desprendimiento de retina intervenidos con VPP ( con o sin cerclaje) en el servicio de oftalmología del Hospital Clínico Universitario Lozano Blesa . Como parámetros a estudiar se recogieron las agudezas visuales previas y posteriores a la cirugía, el estado del cristalino antes y después, la tasa de redesprendimiento y el desarrollo de catarata durante el postoperatorio.Resultados: Se obtuvo una mejoría de la agudeza visual (AV) media prequirúrgica y a 12 meses postquirúrgica de 0,46 a 0, 58 respectivamente en escala decimal, lo cuál no resultó estadísticamente significativo (p>0,05). En la comparación de la evolución de la AV media diferenciando según el estado macular, el grupo macula-on obtuvo una AV media pre-cirugía, al mes, a los 3-6 meses y a los 6-12 meses de 0.66, 0.62, 0.67 y 0.64 respectivamente. En el grupo mácula off se obtuvo una AV media de 0.16, 0.27, 0.37 y 0.64 respectivamente. Siendo estas diferencias entre grupos estadísticamente significativas en el preoperatorio, al mes y a los 3-6 meses. En el análisis de la evolución de la AV diferenciando según la técnica utilizada, el grupo de VPP partió de una AV inicial de 0,6 y el grupo VPP+HE de una AV inicial de 0.36 (p0.05). Se encontró un mayor éxito anatómico con una sola cirugía en el grupo de VPP + HE (84,62 %) que en el grupo de VPP sola (71,43 %), (p>0.05). 7 pacientes (14,89%) desarrollaron catarata en el periodo de seguimiento posterior a la cirugía de DR.Conclusiones: La afectación macular en el desprendimiento de retina supone una disminución visual estadísticamente significativa preoperatoria (pSe evidenció una mejoría clínica de la AV media en pacientes con DRR tras someterse a cirugía para tratar el DRR, ya sea con VPP sola o VPP + HE, aunque este cambio experimentado en la AV no se puede calificar como estadisticamente significativo después de hacer el análisis estadístico. En la comparación de los resultados visuales de media del grupo mácula-on y mácula-off, en la AV inicial, al mes y a los 3-6 meses, la AV media fue mayor en el grupo mácula on (pSe encontró mayor éxito anatómico con una sola cirugía utilizando la cirugía de VPP + HE en lugar de realizar solo VPP (p<br /