Efectos sobre las células pleurales malignas de la hipertermia y cisplatino: síntesis de proteínas pro-inflamatorias y apoptosis celular

En razón de su elevada incidencia y mal pronóstico, la infiltración neoplásica maligna de la pleura supone un importante reto terapéutico en la actualidad, dado que los resultados de los tratamientos disponibles son pobres y en la mayor parte de los casos únicamente implican el control de síntomas. El empleo de la quimioterapia hipertérmica intrapleural podría aportar un mejor control de la enfermedad mejorando la supervivencia y calidad de vida de los pacientes. A pesar de que en los últimos años se han realizado numerosos ensayos de este tipo de tratamiento, sus mecanismos de acción aún no se han aclarado y no es posible establecer, con suficiente evidencia científica, un esquema terapéutico concreto. Teniendo en cuenta la escasa información existente acerca del mecanismo de acción de la quimioterapia hipertérmica a nivel celular se planteó el presente estudio, con el fin de determinar in vitro en células pleurales neoplásicas humanas, el efecto de la hipertermia y el cisplatino en términos de apoptosis celular. Las células empleadas en el estudio fueron tomadas del líquido pleural de pacientes con infiltración pleural neoplásica confirmada histológicamente, a los que se realizó una videotoracoscopia diagnóstica. Como control, se utilizaron células obtenidas del líquido pleural de pacientes afectos de procesos pleurales de naturaleza inflamatoria. Tras la diferenciación en el laboratorio de las células neoplásicas y no neoplásicas presentes en las muestras, se procedió a determinar el porcentaje de apoptosis celular en ambos grupos tras 2 horas de exposición a cisplatino bajo diversas condiciones de temperatura: 37ºC, 40ºC y 42ºC. Así mismo se analizaron las variaciones en la expresión de las principales proteínas implicadas en el proceso apoptótico, producidas por la hipertermia y el citostático en las células pleurales neoplásicas. El efecto aislado de la hipertermia, evidenció inducción de apoptosis en las células inflamatorias pero no así en las células neoplásicas. Se apreció un incremento significativo de la apoptosis en ambos grupos celulares tras el efecto combinado de la hipertermia y el citostático. El porcentaje más elevado de apoptosis en las células neoplásicas, se obtuvo tras la administración de cisplatino a una temperatura de 40ºC. En lo que respecta a las variaciones en la expresión de proteínas implicadas en el proceso apoptótico, el análisis evidenció cambios ostensibles en la expresión de proteínas pro y antiapoptóticas, registrándose los cambios más importantes en la expresión de las mismas tras el efecto combinado de la hipertermia y el cisplatino. También pudieron apreciarse diferentes respuestas en la expresión proteica en función del tipo histológico tumoral de las células estudiadas. Los resultados de nuestro estudio permiten afirmar que el efecto combinado del cisplatino y la elevación de la temperatura del medio a 40ºC durante un tiempo de aplicación de 2 horas, produce in vitro apoptosis efectiva en células pleurales neoplásicas humanas.Departamento de Cirugía, Oftalmología, Otorrinolaringología y Fisioterapi

Hernias diafragmáticas traumáticas

The diafragm is a thin and flat musculo-fascial structure that separates the chest from the abdominal cavity.Traumatic diaphragmatic hernia is an infrequent and life-threatening injury that may happen in patients with severe blunt or penetrating thoracoabdominal trauma. Diaphragmatic rupture is an important indicator of the severity of the trauma.These ruptures may be recognized at the time of the initial trauma, but are diagnosed months or even years later during the follow-up for related symptoms. If it is not detected early, the mortality rate could increase due to severe complications.The diagnosis of traumatic diaphragmatic hernia is difficult and often missed, because it could be accompanied by injuries to other organs. Supine chest radiography, despite its known limitations, is the initial most commonly performed imaging test to evaluate a traumatic injury in the thorax. However, computed tomography (CT) is the imaging tool of choice, as it is the key element for the detection of diaphragmatic injury after trauma.In hemodynamically stable patients, either videolaparoscopy or videothoracoscopy are recommended for the diagnosis and repair of a missed diaphragmatic injury. The surgical repair with nonabsorbable simple sutures is adequate in most cases, and the use of mesh should be reserved for chronic and large defects.El diafragma es una estructura músculo-aponeurótica delgada y aplanada que separa la cavidad torácica de la abdominal. La hernia diafragmática traumática es una lesión poco frecuente y potencialmente mortal que puede presentarse en pacientes que han sufrido un traumatismo tóraco-abdominal tanto cerrado como penetrante. La ruptura diafragmática es un importante indicador de la gravedad del traumatismo. Suelen identificarse en el momento del traumatismo, pero en ocasiones pueden pasar desapercibidas y diagnosticarse meses, e incluso años, más tarde debido a la presencia de síntomas relacionados con las estructuras y órganos afectados. Si no se detecta a tiempo, la tasa de mortalidad puede aumentar debido a la aparición de graves complicaciones. El diagnóstico de la hernia diafragmática traumática es difícil y, a menudo, puede pasar desapercibido debido a la gravedad de las lesiones acompañantes. La radiografía de tórax en decúbito supino, a pesar de sus limitaciones, es el método de imagen más habitual y el más frecuentemente utilizado para evaluar los traumatismos torácicos. Sin embargo, la tomografía computarizada (TAC) es actualmente la exploración idónea y el principal método diagnóstico de las hernias diafragmáticas traumáticas. En pacientes hemodinámicamente estables la videolaparoscopia y la videotoracoscopia permiten el diagnóstico y en muchos casos el tratamiento de la lesión diafragmática. En la mayoría de los casos la sutura de los bordes de la herida diafragmática es suficiente para corregir la lesión. En los grandes defectos diafragmáticos puede ser necesario el uso de prótesis

Zoonotic "Enterocytozoon bieneusi" genotypes in free-ranging and farmed wild ungulates in Spain

Microsporidia comprises a diverse group of obligate, intracellular, and spore-forming parasites that infect a wide range of animals. Among them, Enterocytozoon bieneusi is the most frequently reported species in humans and other mammals and birds. Data on the epidemiology of E. bieneusi in wildlife are limited. Hence, E. bieneusi was investigated in eight wild ungulate species present in Spain (genera Ammotragus, Capra, Capreolus, Cervus, Dama, Ovis, Rupicapra, and Sus) by molecular methods. Faecal samples were collected from free-ranging (n = 1058) and farmed (n = 324) wild ungulates from five Spanish bioregions. The parasite was detected only in red deer (10.4%, 68/653) and wild boar (0.8%, 3/359). Enterocytozoon bieneusi infections were more common in farmed (19.4%, 63/324) than in wild (1.5%, 5/329) red deer. A total of 11 genotypes were identified in red deer, eight known (BEB6, BEB17, EbCar2, HLJD-V, MWC_d1, S5, Type IV, and Wildboar3) and three novel (DeerSpEb1, DeerSpEb2, and DeerSpEb3) genotypes. Mixed genotype infections were detected in 15.9% of farmed red deer. Two genotypes were identified in wild boar, a known (Wildboar3) and a novel (WildboarSpEb1) genotypes. All genotypes identified belonged to E. bieneusi zoonotic Groups 1 and 2. This study provides the most comprehensive epidemiological study of E. bieneusi in Spanish ungulates to date, representing the first evidence of the parasite in wild red deer populations worldwide. Spanish wild boars and red deer are reservoir of zoonotic genotypes of E. bieneusi and might play an underestimated role in the transmission of this microsporidian species to humans and other animal

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Hernias diafragmáticas traumáticas

The diafragm is a thin and flat musculo-fascial structure that separates the chest from the abdominal cavity. Traumatic diaphragmatic hernia is an infrequent and life-threatening injury that may happen in patients with severe blunt or penetrating thoracoabdominal trauma. Diaphragmatic rupture is an important indicator of the severity of the trauma. These ruptures may be recognized at the time of the initial trauma, but are diagnosed months or even years later during the follow-up for related symptoms. If it is not detected early, the mortality rate could increase due to severe complications. The diagnosis of traumatic diaphragmatic hernia is difficult and often missed, because it could be accompanied by injuries to other organs. Supine chest radiography, despite its known limitations, is the initial most commonly performed imaging test to evaluate a traumatic injury in the thorax. However, computed tomography (CT) is the imaging tool of choice, as it is the key element for the detection of diaphragmatic injury after trauma. In hemodynamically stable patients, either videolaparoscopy or videothoracoscopy are recommended for the diagnosis and repair of a missed diaphragmatic injury. The surgical repair with nonabsorbable simple sutures is adequate in most cases, and the use of mesh should be reserved for chronic and large defects.El diafragma es una estructura músculo-aponeurótica delgada y aplanada que separa la cavidad torácica de la abdominal. La hernia diafragmática traumática es una lesión poco frecuente y potencialmente mortal que puede presentarse en pacientes que han sufrido un traumatismo tóraco-abdominal tanto cerrado como penetrante. La ruptura diafragmática es un importante indicador de la gravedad del traumatismo. Suelen identificarse en el momento del traumatismo, pero en ocasiones pueden pasar desapercibidas y diagnosticarse meses, e incluso años, más tarde debido a la presencia de síntomas relacionados con las estructuras y órganos afectados. Si no se detecta a tiempo, la tasa de mortalidad puede aumentar debido a la aparición de graves complicaciones. El diagnóstico de la hernia diafragmática traumática es difícil y, a menudo, puede pasar desapercibido debido a la gravedad de las lesiones acompañantes. La radiografía de tórax en decúbito supino, a pesar de sus limitaciones, es el método de imagen más habitual y el más frecuentemente utilizado para evaluar los traumatismos torácicos. Sin embargo, la tomografía computarizada (TAC) es actualmente la exploración idónea y el principal método diagnóstico de las hernias diafragmáticas traumáticas. En pacientes hemodinámicamente estables la videolaparoscopia y la videotoracoscopia permiten el diagnóstico y en muchos casos el tratamiento de la lesión diafragmática. En la mayoría de los casos la sutura de los bordes de la herida diafragmática es suficiente para corregir la lesión. En los grandes defectos diafragmáticos puede ser necesario el uso de prótesis

Role of age and comorbidities in mortality of patients with infective endocarditis.

The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups: A total of 3120 patients with IE (1327  There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in th

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective