Medical empathy in medical students in Madrid: A proposal for empathy level cut-off points for Spain.

This study evaluates the degree of empathy among medical students and its influencing factors at three critical moments of their degree studies (beginning of first year and end of third and sixth years) as well as establishes low-, medium-, and high-empathy cut-off points to obtain valid and reliable results that can be extrapolated to the general population. This cross-sectional study of the eight (public and private) medical schools in the province of Madrid, used an electronic questionnaire with the Jefferson Scale of Empathy (JSE), Medical Student Well-Being Index, and other independent characteristics as measuring instruments. Of the 2,264 student participants, 1,679 (74.0%) were women, with a 50.7% participation rate. No significant differences were found in empathy levels by academic year. Regarding range, percentile and cut-off point tables were established to identify students with high, medium, and low empathy levels. Women (p<0.001), volunteer workers (p<0.001), and those preferring general specialties (internal medicine, psychiatry, pediatrics, or family medicine) scored higher on the JSE (p<0.02). Moreover, 41.6% presented high level of psychological distress. Women reported a lower well-being level and a higher risk of psychological distress (p = 0.004). In sum, the empathy of medical students in Madrid did not differ among the three critical moments of their university studies. The established cut-off points could be taken into account when accessing the medical degree and identifying students with low levels of empathy to implement curricular interventions to rectify this perceived deficiency. There was a high percentage of medical students with high levels of psychological distress.

Role of surgical manipulation in lung inflammatory response in a model of lung resection surgery.

OBJECTIVES: Lung resection surgery with one-lung ventilation leads to an inflammatory response. Surgical manipulation can play a key role in this response. Sevoflurane, a commonly used volatile anaesthetic, has a proven anti-inflammatory effect. Our main goal was to evaluate the segregated effect of surgical manipulation during lung resection surgery and the protective role of sevoflurane with regard to this response. METHODS: Fifteen pigs underwent left thoracotomy for caudal lobectomy under general anaesthesia. The animals were divided into 3 groups: control, sevoflurane and sham. The animals in the sham group underwent left thoracotomy and one-lung ventilation over 120 min, without lobectomy. The animals in the sevoflurane group received anaesthetic maintenance with sevoflurane. The animals in the sham group and the control group received propofol during the procedure. Lung biopsies were collected before the procedure (left caudal lobe) and 24 h later (right mediastinal lobe and left upper lobe). The samples were stored to measure levels of inflammatory markers (IL-1, TNF-α and ICAM-1), apoptotic mediators (BAD, BAX, BCL-2 and Caspase-3), Syndecan-1, MicroRNAs 182, 145 and lung oedema. RESULTS: Surgical manipulation increased the expression of inflammation (IL-1, TNF-α and ICAM-1) and proapoptotic mediators (BAX, BAD and Caspase-3). It also caused degradation of endothelial glycocalyx (Syndecan-1) and pulmonary oedema. Administration of sevoflurane reduced the elevation of inflammatory markers, degradation of glycocalyx and pulmonary oedema observed in the control group. CONCLUSIONS: Surgical manipulation of the collapsed lung could increase the expression of inflammation and proapoptotic mediators and cause tissue damage in the form of pulmonary oedema. Sevoflurane could attenuate this molecular response and pulmonary oedema.

Procedimiento de autotrasplante pulmonar en el cerdo como modelo experimental para el estudio del síndrome de isquemia-reperfusión / Experimental Swine Lung Autotransplant Model to Study Lung Ischemia-Reperfusion Injury

Introducción: El daño pulmonar agudo por isquemia reperfusión (IR) ha sido estudiado fundamentalmenteen modelos experimentales y clínicos con IR fría. Son limitados los estudios que profundizan en lasalteraciones bioquímicas durante la IR normotérmica (caliente). El objetivo del este trabajo es presentarun modelo de autotrasplante pulmonar en cerdo para el estudio de las fases más precoces del síndromede IR normotérmica pulmonar.Animales y métodos: Seis cerdos de la raza Large-White fueron sometidos a neumonectomía izquierda,lobectomía craneal ex situ, reimplantación del lóbulo caudal y reperfusión del mismo durante 30 min.Durante el procedimiento se analizaron diferentes parámetros para identificar cambios hemodinámicos,gasométricos y bioquímicos en el modelo. El estudio estadístico se realizó con pruebas no paramétricas.Resultados: Tras la isquemia, se observó en tejido pulmonar un aumento significativo (p < 0,05) de metabolitosde peroxidación lipídica, de citoquinas y quemoquinas proinflamatorias (TNF- , IL-1 y MCP-1),de actividad leucocitaria (mieloperoxidasa o MPO), de actividad óxido nítrico sintasa inducible y de laproteína quinasaMAPKp38, mientras que se observóundescenso de actividad tisular de las formas constitutivasde NOS y de monóxido de carbono sérico. Estas alteraciones se mantuvieron o acentuaron durantela reperfusión, donde se observó también una mayor actividad tisular hemo-oxigenasa constitutiva.Conclusiones: Se presenta un procedimiento experimental de IR normotérmica pulmonar describiendo enprofundidad cambios hemodinámicos, gasométricos y bioquímicos. Tanto el modelocomolos parámetrosanalizados podrían ser útiles en el estudio de nuevas terapias moduladoras del da˜no pulmonar agudo ensituaciones clínicas de IR normotérmica(AU)

Introduction: Ischemia-reperfusion (IR) lung injury has been investigated extensively on clinical andexperimental models of cold ischemia. However, relatively few studies examine the detailed biochemicalchanges occurring during normothermic (warm) IR.The objective of this work was to establish an experimental lung autotransplant model to be carried outon pigs in order to study the early stages of normothermic lung IR.Animals y methods: Six Large-White pigs underwent a lung autotransplant which entailed left pneumonectomy,ex situ cranial lobectomy, caudal lobe reimplantation and its reperfusion for 30 min. Throughoutthe procedure, several parameters were measured in order to identify hemodynamic, gasometric andbiochemical changes. Non-parametric statistical analyses were used to compare differences between periods. Results: After ischemia, a significant increase (P < 0.05) in lipid peroxidation metabolites, proinflammatorycytokines and chemokines (TNF- , IL-1 y MCP-1), neutrophil activation, inducible nitric oxide synthaseactivity and protein-kinase MAPK p38 levels were observed in lung tissue. However, constitutive nitricoxide synthase activity in lung tissue and carbon monoxide plasma levels were decrease. The same heldtrue throughout the reperfusion period, when an increase in the constitutive heme-oxygenase activitywas also shown.Conclusions: An experimental model of normothermic lung IR injury is presented and detailed changes inhemodynamic, gasometric and biochemical parameters are shown. Both the model and the studied parametersmay be clinically useful in future investigations testing new therapies to prevent normothermicIR induced lung injury(AU)

Experimental Swine lung autotransplant model to study lung ischemia-reperfusion injury.

INTRODUCTION: Ischemia-reperfusion (IR) lung injury has been investigated extensively on clinical and experimental models of cold ischemia. However, relatively few studies examine the detailed biochemical changes occurring during normothermic (warm) IR. The objective of this work was to establish an experimental lung autotransplant model to be carried out on pigs in order to study the early stages of normothermic lung IR. ANIMALS Y METHODS: Six Large-White pigs underwent a lung autotransplant which entailed left pneumonectomy, ex situ cranial lobectomy, caudal lobe reimplantation and its reperfusion for 30 min. Throughout the procedure, several parameters were measured in order to identify hemodynamic, gasometric and biochemical changes. Non-parametric statistical analyses were used to compare differences between periods. RESULTS: After ischemia, a significant increase (P < 0.05) in lipid peroxidation metabolites, proinflammatory cytokines and chemokines (TNF-α, IL-1ß y MCP-1), neutrophil activation, inducible nitric oxide synthase activity and protein-kinase MAPK p38 levels were observed in lung tissue. However, constitutive nitric oxide synthase activity in lung tissue and carbon monoxide plasma levels were decrease. The same held true throughout the reperfusion period, when an increase in the constitutive heme-oxygenase activity was also shown. CONCLUSIONS: An experimental model of normothermic lung IR injury is presented and detailed changes in hemodynamic, gasometric and biochemical parameters are shown. Both the model and the studied parameters may be clinically useful in future investigations testing new therapies to prevent normothermic IR induced lung injury.

Efecto citoprotector del tacrolimus a dosis bajas sobre islotes de Langeerhans en cultivo sometidos a estímulos por citocinas del rechazo agudo / Cytoprotective effect of low-dose tacrolimus on islets of Langerhans in cultures subjected to stimulation by acute rejection cytokines

Introducción La mejoría de los resultados en el trasplante de islotes pancreáticos se debe en gran parte a la introducción de nuevos protocolos de inmunosupresión que incluyen, entre otros, tacrolimus a bajas dosis. Este fármaco tiene efectos antioxidantes y antiapoptóticos que podrían ser de utilidad en la prevención del rechazo primario. Objetivos Evaluar la respuesta in vitro a tacrolimus a bajas dosis en islotes de rata estimulados con citocinas proinflamatorias implicadas en el rechazo primario de islotes. Material y método Se cultivaron islotes de rata en medio RPMI determinándose producción de lipoperóxido (LPO) y óxido nítrico (NO) y marcadores de apoptosis (nucleosomas y Bcl-2) en presencia de IL-1 (50UI/ml) e IF-γ (1000UI/ml) y adición de tacrolimus (FK-506; 5ng/ml).Resultados Tras la estimulación se apreció un aumento muy significativo (p<0,01) de los marcadores de estrés oxidativo (LPO 10,1±1,16pmol/islote x 24; NO 19,1±3,28pmol/islote x 24h) y apoptosis (nucleosomas 0,24±0,04; Bcl-2 0,69±0,212). Dichos efectos fueron contrarrestados de manera significativa tras añadir tacrolimus, siendo la reversión completa (p NS frente a controles) en el caso de la producción de lipoperóxidos (1,58pmol/islote x 24h) y óxido nítrico (9,81pmol/islote x 24h) así como en el descenso de Bcl-2 (1,37±0,23Ui/islote).Conclusiones El efecto citoprotector in vitro del tacrolimus a bajas dosis sobre islotes estimulados con citocinas proinflamatorias consigue aminorar la generación de estrés oxidativo y la activación de la apoptosis, habitualmente implicados en el rechazo en las primeras 48h postimplante (AU)

Introduction The improvement in pancreatic islet transplantation results is due to immunosuppression protocols that include, among others, low-dose tacrolimus. Both anti-inflammatory and anti-oxidant effects of tacrolimus could be useful in preventing primary rejection. Aim To evaluate in vitro islet low-dose tacrolimus response after pro-inflammatory stimulation. Material and methodsIsolated rat islets were cultured in RPMI medium in the presence of IL-1 (50UI/mL) plus IF-γ (1000UI/mL) and tacrolimus (5ng/mL). The 24h production of lipoperoxide (LPO) and nitric oxide (NO) were measured as oxidative stress markers. Determination of apoptosis markers (nucleo some content and Bcl-2) was also performed. Results Oxidative stress (LPO 10.1±1.16pmol/islet x 24; NO 19.1±3.28pmol/islet x 24h) and apoptosis (nucleosome 0.24±0.04UI/islet; Bcl-2 0.69±0.212UI/islet) markers showed a very significant increase after cytokine stimulation (p<0.01). Both effects improved by adding tacrolimus to the medium. Protective effect was complete when lipoperoxide (1.58pmol/islet x 24h), nitric oxide (9.81pmol/islet x 24h) and Bcl-2 (1.37±0.23UI/islet) were determined. Conclusion In vitro cytoprotective effect of low-dose tacrolimus on isolated rat islets decreases both oxidative stress and apoptosis markers after stimulation of pro-inflammatory mediators (AU)

[Cytoprotective effect of low-dose tacrolimus on islets of Langerhans in cultures subjected to stimulation by acute rejection cytokines]. / Efecto citoprotector del tacrolimus a dosis bajas sobre islotes de Langeerhans en cultivo sometidos a estímulos por citocinas del rechazo agudo.

INTRODUCTION: The improvement in pancreatic islet transplantation results is due to immunosuppression protocols that include, among others, low-dose tacrolimus. Both anti-inflammatory and anti-oxidant effects of tacrolimus could be useful in preventing primary rejection. AIM: To evaluate in vitro islet low-dose tacrolimus response after pro-inflammatory stimulation. MATERIAL AND METHODS: Isolated rat islets were cultured in RPMI medium in the presence of IL-1 (50 UI/mL) plus IF-gamma (1000 UI/mL) and tacrolimus (5 ng/mL). The 24 h production of lipoperoxide (LPO) and nitric oxide (NO) were measured as oxidative stress markers. Determination of apoptosis markers (nucleosome content and Bcl-2) was also performed. RESULTS: Oxidative stress (LPO 10.1+/-1.16 pmol/islet x 24; NO 19.1+/-3.28 pmol/isletx24 h) and apoptosis (nucleosome 0.24+/-0.04 UI/islet; Bcl-2 0.69+/-0.212 UI/islet) markers showed a very significant increase after cytokine stimulation (p<0.01). Both effects improved by adding tacrolimus to the medium. Protective effect was complete when lipoperoxide (1.58 pmol/isletx24 h), nitric oxide (9.81 pmol/isletx24 h) and Bcl-2 (1.37+/-0.23 UI/islet) were determined. CONCLUSION: In vitro cytoprotective effect of low-dose tacrolimus on isolated rat islets decreases both oxidative stress and apoptosis markers after stimulation of pro-inflammatory mediators.

[Current status of islet transplantation]. / Estado actual del trasplante de islotes pancreáticos.

Due to the numerous advances in islet transplantation in the last few years, clinical outcomes following this procedure are continually improving. Novel immunosuppression protocols, improved donor and recipient selection, and careful attention to the process of organ extraction, preservation and islet isolation have contributed to long-term success. The present article reviews the results of clinical islet transplantation and their relationship with the different advances introduced. The use of new islet sources such as living and non-heart-beating donors, as well as recent advances in our knowledge of the mechanisms of rejection and its prevention, are also reviewed.

Estado actual del trasplante de islotes pancreáticos / Current status of islet transplantation

El trasplante de islotes pancreáticos mejora día a día sus resultados clínicos gracias a numerosas mejoras en el proceso desarrolladas en los últimos años. Tanto los nuevos protocolos de inmunosupresión como la selección de los donantes y receptores, así como un especial cuidado en la obtención, preservación y procesamiento de los páncreas, han hecho posible conseguir controles glucémicos prolongados. Uno de los objetivos principales de esta revisión es presentar la evolución de los resultados en humanos a medida que estos cambios han ido introduciéndose. Asimismo, se revisa el empleo de nuevas fuentes de islotes, como son el donante vivo y el donante a corazón parado, junto con los nuevos hallazgos en el conocimiento de los mecanismos de rechazo y las nuevas opciones terapéuticas desarrolladas para prevenirlo (AU)

Due to the numerous advances in islet transplantation in the last few years, clinical outcomes following this procedure are continually improving. Novel immunosuppression protocols, improved donor and recipient selection, and careful attention to the process of organ extraction, preservation and islet isolation have contributed to long-term success. The present article reviews the results of clinical islet transplantation and their relationship with the different advances introduced. The use of new islet sources such as living and non-heart-beating donors, as well as recent advances in our knowledge of the mechanisms of rejection and its prevention, are also reviewed (AU)