Repercusión de vortioxetina sobre la función sexual frente a otros antidepresivos / Impact of vortioxetine on sexual function compared to other antidepressants

Objetivo Analizar la repercusión del antidepresivo vortioxetina sobre la función sexual, frente a inhibidores selectivos de la recaptación de serotonina (ISRS) e inhibidores selectivos mixtos de la recaptación de serotonina y noradrenalina (IRSN o Duales) en pacientes con depresión. Material y métodos Estudio analítico, observacional, longitudinal y prospectivo en el que se incluyeron hombres y mujeres mayores de 18años con trastorno depresivo y actividad sexual en pareja, separándolos en dos grupos: 1)de estudio: inician tratamiento con vortioxetina; 2)control: mantienen tratamiento con ISRS o Duales. Se realizaron tres visitas: inclusión, seguimiento a las 4semanas y final 3meses desde la inclusión. El periodo total de seguimiento fue de 3meses. Resultados Se incluyeron 87 pacientes (edad media, 46,85años). Al final del estudio se hallaron diferencias significativas (DS) en el valor medio de la suma de las puntuaciones de los dominios evaluadores de la respuesta sexual del cuestionario de Función Sexual de la Mujer (FSM-2) entre el grupo de estudio y el de control (22,42±4,39 y 16,13±7,76, respectivamente), con menor riesgo de disfunción sexual en las mujeres tratadas con vortioxetina. También menor riesgo de disfunción sexual en estas mismas mujeres en los dominios de deseo, lubricación, orgasmo, frecuencia sexual y satisfacción sexual. Estas diferencias no se hallaron al evaluar la función sexual masculina. Conclusiones Las mujeres tratadas con vortioxetina presentaron mejor función sexual que las tratadas con ISRS o Duales y menor riesgo de disfunción sexual (AU)

Objective To analyze the impact of the antidepressant vortioxetine on sexual function, compared to selective serotonin reuptake inhibitors (SSRIs) and mixed selective serotonin and norepinephrine reuptake inhibitors (IRSN or Dual) in patients with depression. Material and methods Analytical, observational, longitudinal and prospective study, which included men and women over 18years of age, with depressive disorder and sexual activity with a partner, separating them into two groups: (i)study, starting treatment with vortioxetine; (2)control, maintaining treatment with SSRIs or Duals. Three visits were made: inclusion, follow-up at 4weeks and final 3months from inclusion. The total follow-up period was 3months. Results A total of 87 patients were included (mean age 46.85years). At the end of the study, significant differences (SD) were found in the mean value of the sum of the scores of the evaluative domains of the sexual response of the Women's Sexual Function Questionnaire (FSM-2) between the study group and the control (22.42±4.39 and 16.13±7.76, respectively), with a lower risk of sexual dysfunction in women treated with vortioxetine. Also, lower risk of sexual dysfunction in these same women in the domains of desire, lubrication, orgasm, sexual frequency and sexual satisfaction. These differences were not found when assessing male sexual function. Conclusions Women treated with vortioxetine presented better sexual function than those treated with SSRIs or Duals and a lower risk of sexual dysfunction (AU)

[Impact of vortioxetine on sexual function compared to other antidepressants]. / Repercusión de vortioxetina sobre la función sexual frente a otros antidepresivos.

OBJECTIVE: To analyze the impact of the antidepressant vortioxetine on sexual function, compared to selective serotonin reuptake inhibitors (SSRIs) and mixed selective serotonin and norepinephrine reuptake inhibitors (IRSN or Dual) in patients with depression. MATERIAL AND METHODS: Analytical, observational, longitudinal and prospective study, which included men and women over 18years of age, with depressive disorder and sexual activity with a partner, separating them into two groups: (i)study, starting treatment with vortioxetine; (2)control, maintaining treatment with SSRIs or Duals. Three visits were made: inclusion, follow-up at 4weeks and final 3months from inclusion. The total follow-up period was 3months. RESULTS: A total of 87 patients were included (mean age 46.85years). At the end of the study, significant differences (SD) were found in the mean value of the sum of the scores of the evaluative domains of the sexual response of the Women's Sexual Function Questionnaire (FSM-2) between the study group and the control (22.42±4.39 and 16.13±7.76, respectively), with a lower risk of sexual dysfunction in women treated with vortioxetine. Also, lower risk of sexual dysfunction in these same women in the domains of desire, lubrication, orgasm, sexual frequency and sexual satisfaction. These differences were not found when assessing male sexual function. CONCLUSIONS: Women treated with vortioxetine presented better sexual function than those treated with SSRIs or Duals and a lower risk of sexual dysfunction.

A Unifying Framework for Understanding Biological Structures and Functions Across Levels of Biological Organization.

The relationship between structure and function is a major constituent of the rules of life. Structures and functions occur across all levels of biological organization. Current efforts to integrate conceptual frameworks and approaches to address new and old questions promise to allow a more holistic and robust understanding of how different biological functions are achieved across levels of biological organization. Here, we provide unifying and generalizable definitions of both structure and function that can be applied across all levels of biological organization. However, we find differences in the nature of structures at the organismal level and below as compared to above the level of the organism. We term these intrinsic and emergent structures, respectively. Intrinsic structures are directly under selection, contributing to the overall performance (fitness) of the individual organism. Emergent structures involve interactions among aggregations of organisms and are not directly under selection. Given this distinction, we argue that while the functions of many intrinsic structures remain unknown, functions of emergent structures are the result of the aggregate of processes of individual organisms. We then provide a detailed and unified framework of the structure-function relationship for intrinsic structures to explore how their unknown functions can be defined. We provide examples of how these scalable definitions applied to intrinsic structures provide a framework to address questions on structure-function relationships that can be approached simultaneously from all subdisciplines of biology. We propose that this will produce a more holistic and robust understanding of how different biological functions are achieved across levels of biological organization.

A multicenter randomized open-label clinical trial for convalescent plasma in patients hospitalized with COVID-19 pneumonia.

BACKGROUNDPassive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19. Evidence from controlled clinical trials is inconclusive.METHODSWe conducted a randomized, open-label, controlled clinical trial at 27 hospitals in Spain. Patients had to be admitted for COVID-19 pneumonia within 7 days from symptom onset and not on mechanical ventilation or high-flow oxygen devices. Patients were randomized 1:1 to treatment with CP in addition to standard of care (SOC) or to the control arm receiving only SOC. The primary endpoint was the proportion of patients in categories 5 (noninvasive ventilation or high-flow oxygen), 6 (invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), or 7 (death) at 14 days. Primary analysis was performed in the intention-to-treat population.RESULTSBetween April 4, 2020, and February 5, 2021, 350 patients were randomly assigned to either CP (n = 179) or SOC (n = 171). At 14 days, proportion of patients in categories 5, 6, or 7 was 11.7% in the CP group versus 16.4% in the control group (P = 0.205). The difference was greater at 28 days, with 8.4% of patients in categories 5-7 in the CP group versus 17.0% in the control group (P = 0.021). The difference in overall survival did not reach statistical significance (HR 0.46, 95% CI 0.19-1.14, log-rank P = 0.087).CONCLUSIONCP showed a significant benefit in preventing progression to noninvasive ventilation or high-flow oxygen, invasive mechanical ventilation or ECMO, or death at 28 days. The effect on the predefined primary endpoint at 14 days and the effect on overall survival were not statistically significant.TRIAL REGISTRATIONClinicaltrials.gov, NCT04345523.FUNDINGGovernment of Spain, Instituto de Salud Carlos III.

Venovenous extracorporeal membrane oxygenation as a bridge to traumatic bronchial fistula closure. / Membrana de oxigenación extracorpórea venovenosa como puente a la reparación de una fístula bronquial traumática.

Traumatic tracheobronchial injuries occur in 1% of patients with thoracic trauma, most of them dying at the site of the trauma. In this case report, we present a 26-year-old female patient admitted to the ICU due to a blunt chest trauma causing life threatening hypoxaemia and acidosis; deciding to implant percutaneous venovenous extracorporeal membrane oxygenation. The use of percutaneous venovenous extracorporeal membrane oxygenation, implemented with a lower anticoagulation target, allowed the diagnosis and treatment of a bronchopleural fistula under conditions of respiratory and hemodynamic stability without haemorrhagic complications, obtaining a fast and adequate assistance achieving the survival of the patient.

Analysis of the relationship between cognitive skills and unilateral sensory hearing loss. / Análisis de la relación entre habilidades cognitivas e hipoacusia sensorial severa unilateral.

OBJECTIVE: To analyse cognitive skills in patients with severe unilateral hearing loss versus those in subjects with normal hearing. METHODS: 40 adults participated: 20 patients (10 women and 10 men) with severe unilateral hearing loss and 20 healthy subjects matched to the study group. Cognitive abilities were measured with the Spanish version of the Woodcock Johnson Battery-Revised; central auditory processing was assessed with monaural psychoacoustic tests. Box plots were drawn and t tests were performed for samples with a significance of P≤.05. RESULTS: A comparison of performances on the filtered word testing and time-compressed disyllabic word tests between patients and controls revealed a statistically significant difference (P≤.05) with greater variability among responses by hearing impaired subjects. This same group also showed a better cognitive performance on the numbers reversed, visual auditory learning, analysis synthesis, concept formation, and incomplete words tests. CONCLUSIONS: Patients with hearing loss performed more poorly than controls on the filtered word and time-compressed disyllabic word tests, but more competently on memory, reasoning, and auditory processing tasks. Complementary tests, such as those assessing central auditory processes and cognitive ability tests, are important and helpful for designing habilitation/rehabilitation and therapeutic strategies intended to optimise and stimulate cognitive skills in subjects with unilateral hearing impairment.

Correction: A study of the depth and size of concave cube Au nanoparticles as highly sensitive SERS probes.

Correction for 'A study of the depth and size of concave cube Au nanoparticles as highly sensitive SERS probes' by J. M. Romo-Herrera et al., Nanoscale, 2016, 8, 7326-7333.

A study of the depth and size of concave cube Au nanoparticles as highly sensitive SERS probes.

High and uniform near fields are localized at the eight similar sharp corners of cubic gold nanoparticles. Moreover, by introducing concavity in the particle lateral planes, such field intensities can be further increased and tuned in the near infrared region without altering the overall size of the nanoparticles. Herein, we perform a thorough investigation of the morphological, crystallographic and plasmonic properties of concave gold nanocubes (GNCs) in the sub-70 nm size range, for their potential application as highly efficient SERS substrates in size-limiting cases. Theoretical calculations indicate that the highest increment of the near-field is located at the eight sharp tips and, interestingly, a medium near-field increment is also activated over the volume next to the concave surface. Remarkably, the plasmonic response of the concave cubic morphology showed great sensitivity to the concavity degree. Experimental SERS analysis nicely matches the outcome of the theoretical model, confirming that medium-sized concave GNCs (35 nm side length) possess the highest SERS activity upon excitation with a 633 nm laser, whereas larger 61 nm side concave GNCs dominate the optical response at 785 nm. Due to their size-intensity trade off, we envision that such small concave gold nanocubes can provide a highly active and efficient SERS platform for size-limiting applications, especially when near infrared excitations are required.

The effect of WIN 55,212-2 suggests a cannabinoid-sensitive component in the early toxicity induced by organic acids accumulating in glutaric acidemia type I and in related disorders of propionate metabolism in rat brain synaptosomes.

Several physiological processes in the CNS are regulated by the endocannabinoid system (ECS). Cannabinoid receptors (CBr) and CBr agonists have been involved in the modulation of the N-methyl-D-aspartate receptor (NMDAr) activation. Glutaric (GA), 3-hydroxyglutaric (3-OHGA), methylmalonic (MMA) and propionic (PA) acids are endogenous metabolites produced and accumulated in the brain of children affected by severe organic acidemias (OAs) with neurodegeneration. Oxidative stress and excitotoxicity have been involved in the toxic pattern exerted by these organic acids. Studying the early pattern of toxicity exerted by these metabolites is crucial to explain the extent of damage that they can produce in the brain. Herein, we investigated the effects of the synthetic CBr agonist WIN 55,212-2 (WIN) on early markers of GA-, 3-OHGA-, MMA- and PA-induced toxicity in brain synaptosomes from adult (90-day-old) and adolescent (30-day-old) rats. As pre-treatment, WIN exerted protective effects on the GA- and MMA-induced mitochondrial dysfunction, and prevented the reactive oxygen species (ROS) formation and lipid peroxidation induced by all metabolites. Our findings support a protective and modulatory role of cannabinoids in the early toxic events elicited by toxic metabolites involved in OAs.

Toxic synergism between quinolinic acid and organic acids accumulating in glutaric acidemia type I and in disorders of propionate metabolism in rat brain synaptosomes: Relevance for metabolic acidemias.

The brain of children affected by organic acidemias develop acute neurodegeneration linked to accumulation of endogenous toxic metabolites like glutaric (GA), 3-hydroxyglutaric (3-OHGA), methylmalonic (MMA) and propionic (PA) acids. Excitotoxic and oxidative events are involved in the toxic patterns elicited by these organic acids, although their single actions cannot explain the extent of brain damage observed in organic acidemias. The characterization of co-adjuvant factors involved in the magnification of early toxic processes evoked by these metabolites is essential to infer their actions in the human brain. Alterations in the kynurenine pathway (KP) - a metabolic route devoted to degrade tryptophan to form NAD(+) - produce increased levels of the excitotoxic metabolite quinolinic acid (QUIN), which has been involved in neurodegenerative disorders. Herein we investigated the effects of subtoxic concentrations of GA, 3-OHGA, MMA and PA, either alone or in combination with QUIN, on early toxic endpoints in rat brain synaptosomes. To establish specific mechanisms, we pre-incubated synaptosomes with different protective agents, including the endogenous N-methyl-d-aspartate (NMDA) receptor antagonist kynurenic acid (KA), the antioxidant S-allylcysteine (SAC) and the nitric oxide synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME). While the incubation of synaptosomes with toxic metabolites at subtoxic concentrations produced no effects, their co-incubation (QUIN+GA, +3-OHGA, +MMA or +PA) decreased the mitochondrial function and increased reactive oxygen species (ROS) formation and lipid peroxidation. For all cases, this effect was partially prevented by KA and l-NAME, and completely avoided by SAC. These findings suggest that early damaging events elicited by organic acids involved in metabolic acidemias can be magnified by toxic synergism with QUIN, and this process is mostly mediated by oxidative stress, and in a lesser extent by excitotoxicity and nitrosative stress. Therefore, QUIN can be hypothesized to contribute to the pathophysiology of brain degeneration in children with metabolic acidemias.

Cannabinoid receptor agonists reduce the short-term mitochondrial dysfunction and oxidative stress linked to excitotoxicity in the rat brain.

The endocannabinoid system (ECS) is involved in a considerable number of physiological processes in the Central Nervous System. Recently, a modulatory role of cannabinoid receptors (CBr) and CBr agonists on the reduction of the N-methyl-d-aspartate receptor (NMDAr) activation has been demonstrated. Quinolinic acid (QUIN), an endogenous analog of glutamate and excitotoxic metabolite produced in the kynurenine pathway (KP), selectively activates NMDAr and has been shown to participate in different neurodegenerative disorders. Since the early pattern of toxicity exerted by this metabolite is relevant to explain the extent of damage that it can produce in the brain, in this work we investigated the effects of the synthetic CBr agonist WIN 55,212-2 (WIN) and other agonists (anandamide or AEA, and CP 55,940 or CP) on early markers of QUIN-induced toxicity in rat striatal cultured cells and rat brain synaptosomes. WIN, AEA and CP exerted protective effects on the QUIN-induced loss of cell viability. WIN also preserved the immunofluorescent signals for neurons and CBr labeling that were decreased by QUIN. The QUIN-induced early mitochondrial dysfunction, lipid peroxidation and reactive oxygen species (ROS) formation were also partially or completely prevented by WIN pretreatment, but not when this CBr agonist was added simultaneously with QUIN to brain synaptosomes. These findings support a neuroprotective and modulatory role of cannabinoids in the early toxic events elicited by agents inducing excitotoxic processes.

Integrin-driven monocyte to dendritic cell conversion in modified extracorporeal photochemotherapy.

Due to clinical efficacy and safety profile, extracorporeal photochemotherapy (ECP) is a commonly used cell treatment for patients with cutaneous T cell lymphoma (CTCL) and graft-versus-host disease (GVHD). The capacity of ECP to induce dendritic antigen-presenting cell (DC)-mediated selective immunization or immunosuppression suggests a novel mechanism involving pivotal cell signalling processes that have yet to be clearly identified as related to this procedure. In this study we employ two model systems of ECP to dissect the role of integrin signalling and adsorbed plasma proteins in monocyte-to-DC differentiation. We demonstrate that monocytes that were passed through protein-modified ECP plates adhered transiently to plasma proteins, including fibronectin, adsorbed to the plastic ECP plate and activated signalling pathways that initiate monocyte-to-DC conversion. Plasma protein adsorption facilitated 54·2 ± 4·7% differentiation, while fibronectin supported 29·8 ± 7·2% differentiation, as detected by DC phenotypic expression of membrane CD80 and CD86, as well as CD36, human leucocyte antigen D-related (HLA-DR) and cytoplasmic CD83. Further, we demonstrate the ability of fibronectin and other plasma proteins to act through cell adhesion via the ubiquitous arginine-glycine-aspartic (RGD) motif to drive monocyte-to-DC differentiation, with high-density RGD substrates supporting 54·1 ± 5·8% differentiation via αVß3 and α5ß1integrin signalling. Our results demonstrate that plasma protein binding integrins and plasma proteins operate through specific binding domains to induce monocyte-to-DC differentiation in ECP, providing a mechanism that can be harnessed to enhance ECP efficacy.

Early modulation of the transcription factor Nrf2 in rodent striatal slices by quinolinic acid, a toxic metabolite of the kynurenine pathway.

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor involved in the orchestration of antioxidant responses. Although its pharmacological activation has been largely hypothesized as a promising tool to ameliorate the progression of neurodegenerative events, the actual knowledge about its modulation in neurotoxic paradigms remains scarce. In this study, we investigated the early profile of Nrf2 modulation in striatal slices of rodents incubated in the presence of the toxic kynurenine pathway metabolite, quinolinic acid (QUIN). Tissue slices from rats and mice were obtained and used throughout the experiments in order to compare inter-species responses. Nuclear Nrf2 protein levels and oxidative damage to lipids were compared. Time- and concentration-response curves of all markers were explored. Nrf2 nuclear activation was corroborated through phase 2 antioxidant protein expression. The effects of QUIN on Nrf2 modulation and oxidative stress were also compared between slices of wild-type (Nrf2(+/+)) and Nrf2 knock-out (Nrf2(-/-)) mice. The possible involvement of the N-methyl-d-aspartate receptor (NMDAr) in the Nrf2 modulation and lipid peroxidation was further explored in mice striatal slices. In rat striatal slices, QUIN stimulated the Nrf2 nuclear translocation. This effect was accompanied by augmented lipid peroxidation. In the mouse striatum, QUIN per se exerted an induction of Nrf2 factor only at 1h of incubation, and a concentration-response effect on lipid peroxidation after 3h of incubation. QUIN stimulated the striatal content of phase 2 enzymes. Nrf2(-/-) mice were slightly more responsive than Nrf2(+/+) mice to the QUIN-induced oxidative damage, and completely unresponsive to the NMDAr antagonist MK-801 when tested against QUIN. Findings of this study indicate that: (1) Nrf2 is modulated in rodent striatal tissue in response to QUIN; (2) Nrf2(-/-) striatal tissue was moderately more vulnerable to oxidative damage than the Wt condition; and (3) early Nrf2 up-regulation reflects a compensatory response to the QUIN-induced oxidative stress in course as part of a general defense system, whereas Nrf2 down-regulation might contribute to more intense oxidative cell damage.

Heme oxygenase-1 (HO-1) upregulation delays morphological and oxidative damage induced in an excitotoxic/pro-oxidant model in the rat striatum.

Quinolinic acid (QA)-induced overactivation of N-methyl-d-aspartate receptors yields excitotoxicity, oxidative stress and mitochondrial dysfunction, which altogether contribute to trigger a wide variety of toxic pathways with biochemical, behavioral and neuropathological alterations similar to those observed in Huntington's disease. Noteworthy, in the brains of these patients, increased expression of heme oxygenase-1 (HO-1) levels can be found. It has been proposed that this enzyme can exert a dual role, as it can be either protective or deleterious to the CNS. While some evidence indicates that its overexpression affords cellular anti-oxidant protection due to decreased concentrations of its pro-oxidative substrate heme group, and increased bilirubin levels, other reports established that high HO-1 expression and activity may result in a pro-oxidizing atmosphere due to a release of Fe(2+). In this work, we examined the temporal evolution of oxidative damage to proteins, HO-1 expression, immunoreactivity, total activity, and cell death after 1, 3, 5 and 7 days of an intrastriatal QA infusion (240 nmol/µl). QA was found to induce cellular degeneration, increasing carbonylated proteins and generating a transitory response in HO-1 mRNA, protein content, and immunoreactivity and activity in nerve cells. In order to study the role of HO-1 in the QA-induced cellular death, the tin protoporphyrin IX (SnPP), a well-known HO inhibitor, was administered to rats (30 µmol/kg, i.p.). The administration of SnPP to animals treated with QA inhibited the HO activation, and exacerbated the striatal cell damage induced by QA. Our findings reveal a potential modulatory role of HO-1 in the toxic paradigm evoked by QA in rats. This evidence provides a valuable tool for further approaches on HO-1 regulation in neurotoxic paradigms.

Infección del sitio de salida de los catéteres venosos centrales y su asociación con bacteriemia relacionada con catéter / Infection of the exit site central venous catheters and its association with bacteremia related to catheter

Introducción: Los catéteres venosos centrales (CVC) plantean un alto riesgo de infección. La infección del sitio de salida (ISS-CVC) es la menos estudiada, y se desconoce su asociación con la bacteriemia asociada a catéter (BAC) y su impacto en la evolución del paciente. Objetivo: Evaluar la asociación entre ISS-CVC, BAC y mortalidad. Materiales y métodos: Estudio prospectivo, de observación. Pacientes internados en una Unidad de Terapia Intensiva médico/quirúrgica que requirieron la colocación de CVC desde el 01/06/2010 hasta el 01/04/2012. Se evaluaron datos epidemiológicos, BAC (según criterios de los CDC) y gérmenes. Se utilizaron media ± DE, mediana y rango intercuartílico, y porcentajes. Resultados: Durante este período, ingresaron 575 pacientes, el 98% requirió CVC. Datos de los pacientes: edad 41 ± 26 años, APACHE II 15 ± 7, 96% con ventilación mecánica, días de ventilación mecánica 41 (33-63), días de internación 43 (25-67). Todos los CVC con ISS fueron retirados y cultivados. Se observaron 51 ISS: 5,5/1000-días-catéter: 33% subclavia, 38% yugular, 29% femoral. Seis pacientes con ISS (12%) tuvieron BAC (0,65/1000-días-catéter): 3 subclavias, 2 yugulares, 1 femoral; 2 con halo y 8 con secreción purulenta. Tiempo de permanencia del CVC: 7,5 días (5-10). Clínica al momento de la ISS: shock 50%, fiebre 83%, SOFA 6 ± 3. El 83% de las infecciones fueron monomicrobianas: 83% por bacilos gramnegativos (2 Klebsiella, 2 Pseudomonas, 1 Serratia y 1 Acinetobacter), 17% por enterococos resistentes a vancomicina. La mortalidad fue del 50%. Conclusión: Aunque la ISS provocó una baja incidencia de BAC, la mortalidad fue alta. Al parecer, la ISS no es un factor predictivo de BAC.(AU)

Introduction: Central venous catheters (CVC) are widely used and pose a high risk of infection. There are few studies on insertion site infection (ISI-CVC), and both its association with catheter-associated bloodstream infection (CABSI) and the outcome of patients are unknown. Objective: To determine the association between ISI-CVC, the presence of CABSI and mortality. Materials and methods: Prospective observational study. All patients admitted to a medical/surgical Intensive Care Unit requiring CVC insertion from 06/01/2010 to 04/01/2012 were included. Epidemiological data, CABSI (according to CDC criteria) and microorganisms involved were evaluated. Mean ± SD, median and interquartile range, and percentages were used. Results: During the period study, 575 patients were admitted, 98% required CVC. Patient´s data: age 41 ± 26 years, APACHE II 15 ± 7, 96% on mechanical ventilation, days on mechanical ventilation: 41 (33-63), length of stay 43 (25-67) days. All CVCs with ISI were removed and cultured. Fifty one ISI were observed (5.5/1000-catheter-day). Six patients with ISI (12%) presented CABSI (0.65/1000-catheter-day): 3 in subclavian, 2 in jugular, 1 femoral; 2 with erythema and 8 with purulent secretion. CVC permanence: 7.5 day (5-10). Signs and/or symptoms at the moment of ISI: shock 50%, fever 83%, SOFA 6 ± 3. The 83% of infections were caused by one microorganism: 83% due to gram-negative bacilli (2 Klebsiella, 2 Pseudomonas, 1 Serratia, and 1 Acinetobacter), 17% due to vancomycin-resistant enterococci. The mortality rate was 50%. Conclusion: Although ISI-CVC presented a low incidence of CABSI, mortality rate was high. The ISI-CVC might have a little predictable value for CABSI.(AU)

Consenso de la SEPG sobre la depresión en el anciano / Consensus of the SEPG on depression in the elderly

Antecedentes. La limitación del conocimiento clínico epidemiológico y de la evidencia sobre efectividad terapéutica en la depresión en los pacientes ancianos y muy ancianos genera una excesiva variabilidad de prácticas en la atención clínica a estos pacientes en nuestro sistema sanitario. La Sociedad Española de Psicogeriatría (SEPG) se plantea la necesidad de unificar criterios mediante un método estructurado de consenso profesional. Objetivos. Desarrollar un consenso experto de recomendaciones clínicas para optimizar el abordaje clínico de la depresión en el paciente anciano en España, bajo auspicio de la Sociedad Española de Psicogeriatría (SEPG).Métodos. Consenso Delphi modificado en dos rondas. El estudio se efectuó en cuatro fases: 1) constitución de un comité científico, impulsor del proyecto y responsable de la revisión bibliográfica y de la formulación de las recomendaciones a debate; 2) constitución de un panel experto multicéntrico con representantes de la especialidad; 3) encuesta postal en dos rondas con procesamiento intermedio de opinión ese informe a los panelistas; y 4) discusión de resultados en sesión presencial del comité científico. Resultados. 61 expertos consultados completaron las dos rondas de evaluación del cuestionario. En la primera rondase logran consensuar 39 de las 54 cuestiones analizadas. Tras la interacción del panel se aumenta el consenso hasta un total de 46 ítems de la encuesta (85% de los contenidos propuestos). En las 8 cuestiones restantes no se consigue un consenso suficientemente unánime, bien por disparidad de opiniones entre los profesionales, bien por falta de criterio establecido en la mayoría de los expertos. Conclusiones. Se presenta un amplio listado de criterios profesionales y recomendaciones clínicas que pretenden racionalizar el manejo de la depresión en el paciente anciano y reducir el exceso de variabilidad en la práctica clínica. Las recomendaciones se cualifican según el grado de acuerdo profesional en que se sustentan y pueden considerarse vigentes hasta la aparición de nueva información científica que justifique su revisión (AU)

Background. The limitation of clinical-epidemiological know-how and evidence regarding therapeutic efficiency in depression among the elderly and extremely elderly patients has given rise to an excessive variety of practices in clinical care of these patients in the Spanish health system. The Spanish Society of Psychogeriatrics (SEPG) has raised the question of the need to unify criteria through a structured approach based on professional consensus. Objectives. To develop an expert consensus of clinical recommendations to improve the clinical treatment of depression in elderly patients in Spain, sponsored by the Spanish Society of Psychogeriatrics (SEPG). Methods. Modified Delphi Consensus, in two rounds. The study was conducted in four phases: 1) constitution of a Scientific Committee, project promoter and responsible for bibliographic review and formulation of recommendations for discussion 2) constitution of a multicenter Panel of Experts with representatives from this specialist field 3) postal survey comprised of two rounds, with interim processing of opinions and a report for the experts and 4) discussion of results during an onsite meeting of the Scientific Committee. Results. The survey evaluation was completed by 61experts consulted, in two rounds. In the first round, consensus was reached in 39 of the 54 questions analyzed. Following interaction by the panel, this consensus was increased to a total of 46 survey items (85% of the proposed contents). It was impossible to obtain a sufficiently unanimous consensus on the remaining 8questions, either due to differences of opinion among the professionals or a lack of established criterion in most of the experts. Conclusions. A full list of criteria and clinical recommendations for the purpose of rationalizing the treatment of depression in elderly patients and reducing excessive variability in clinical practice is presented. The recommendations are qualified in accordance with the degree of consensus of the professionals endorsing the mand can be considered valid until new scientific information becomes available that justifies their review (AU)

Consensus of the SEPG on depression in the elderly.

BACKGROUND: The limitation of clinical-epidemiological know-how and evidence regarding therapeutic efficiency in depression among the elderly and extremely elderly patients has given rise to an excessive variety of practices in clinical care of these patients in the Spanish health system. The Spanish Society of Psychogeriatrics (SEPG) has raised the question of the need to unify criteria through a structured approach based on professional consensus. OBJECTIVES: To develop an expert consensus of clinical recommendations to improve the clinical treatment of depression in elderly patients in Spain, sponsored by the Spanish Society of Psychogeriatrics (SEPG). METHODS: Modified Delphi Consensus, in two rounds. The study was conducted in four phases: 1) constitution of a Scientific Committee, project promoter and responsible for bibliographic review and formulation of recommendations for discussion 2) constitution of a multicenter Panel of Experts with representatives from this specialist field 3) postal survey comprised of two rounds, with interim processing of opinions and a report for the experts and 4) discussion of results during an on-site meeting of the Scientific Committee. RESULTS: The survey evaluation was completed by 61 experts consulted, in two rounds. In the first round, consensus was reached in 39 of the 54 questions analyzed. Following interaction by the panel, this consensus was increased to a total of 46 survey items (85% of the proposed contents). It was impossible to obtain a sufficiently unanimous consensus on the remaining 8 questions, either due to differences of opinion among the professionals or a lack of established criterion in most of the experts. CONCLUSIONS: A full list of criteria and clinical recommendations for the purpose of rationalizing the treatment of depression in elderly patients and reducing excessive variability in clinical practice is presented. The recommendations are qualified in accordance with the degree of consensus of the professionals endorsing them and can be considered valid until new scientific information becomes available that justifies their review.

DNA copy number aberrations in small-cell lung cancer reveal activation of the focal adhesion pathway.

Small-cell lung cancer (SCLC) is the most aggressive subtype of lung cancer in its clinical behavior, with a 5-year overall survival as low as 5%. Despite years of research in the field, molecular determinants of SCLC behavior are still poorly understood, and this deficiency has translated into an absence of specific diagnostics and targeted therapeutics. We hypothesized that tumor DNA copy number alterations would allow the identification of molecular pathways involved in SCLC progression. Array comparative genomic hybridization was performed on DNA extracted from 46 formalin-fixed paraffin-embedded SCLC tissue specimens. Genomic profiling of tumor and sex-matched control DNA allowed the identification of 70 regions of copy number gain and 55 regions of copy number loss. Using molecular pathway analysis, we found a strong enrichment in these regions of copy number alterations for 11 genes associated with the focal adhesion pathway. We verified these findings at the genomic, gene expression and protein level. Focal Adhesion Kinase (FAK), one of the central genes represented in this pathway, was commonly expressed in SCLC tumors and constitutively phosphorylated in SCLC cell lines. Those were poorly adherent to most substrates but not to laminin-322. Inhibition of FAK phosphorylation at Tyr(397) by a small-molecule inhibitor, PF-573,228, induced a dose-dependent decrease of adhesion and an increase of spreading in SCLC cell lines on laminin-322. Cells that tended to spread also showed a decrease in focal adhesions, as demonstrated by a decreased vinculin expression. These results support the concept that pathway analysis of genes in regions of copy number alterations may uncover molecular mechanisms of disease progression and demonstrate a new role of FAK and associated adhesion pathways in SCLC. Further investigations of FAK at the functional level may lead to a better understanding of SCLC progression and may have therapeutic implications.