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Resumen Objetivos El acido tranexamico se utiliza para prevenir la hiperfibrinolisis y disminuir el sangrado postoperatorio y el empleo de hemoderivados en cirugia cardiaca con circulacion extracorporea. Este trabajo evalua la eficacia de dosis bajas o altas de acido tranexamico mediante un estudio de cohortes, prospectivo, realizado en 2 hospitales de Valencia. Material y metodos Se seleccionaron 427 pacientes, 207 en el Hospital General Universitario (dosis bajas [DB]) y 220 en el Hospital Universitario y Politecnico La Fe (dosis intermedias [DI] y dosis altas [DA]), entre enero de 2019 y enero de 2020. Se estudio la presencia de hiperfibrinolisis por tromboelastometria rotacional, la administracion de hemoderivados en el intra y postoperatorio, el debito por drenajes en las 12 primeras horas postoperatorias y la aparicion de convulsiones. Se realizo un analisis comparativo univariante y multivariante. El analisis univariante de todas las categorias se llevo a cabo tras realizar un emparejamiento por indice de propension entre DB y DA, y entre DB y DI. Resultados No hubo diferencias estadisticamente significativas en la hiperfibrinolisis, la administracion de concentrados de hematies, el debito por drenajes en las 12 primeras horas ni la aparicion de convulsiones. El grupo DB recibio menos fibrinogeno que el grupo DA (p = 0,014) y DI (p = 0,040). En cambio, la cantidad de plasma fresco congelado administrado al grupo DB fue significativamente superior a la del grupo DI (p = 0,0002). Conclusiones La administracion de dosis bajas de acido tranexamico es tan efectiva como la de dosis mas elevadas en la profilaxis de la hiperfibrinolisis y la prevencion del sangrado postoperatorio en cirugia cardiaca.

Our research team compared the performance of matrix-assisted laser desorption/ionization followed by a time of flight (MALDI-TOF) mass spectrometry and genomic DNA extraction followed by sequencing, assembly and alignment for phylogenetic assessment. We performed these comparisons to determine our methodology’s overall efficacy and accuracy for environmental bacteria. In addition, we collected samples from various contaminated rivers in the Dominican Republic. For both methods, we analyzed these results and reported the main differences between each method.

Resumen La ecocardiografia transesofagica (ETE) es una herramienta fundamental en el intraoperatorio y postoperatorio de cirugia cardiaca con una gran difusion en los ultimos anos. El objetivo de este trabajo es conocer la situacion actual de la ETE en el ambito de la anestesiologia en cirugia cardiaca en Espana a traves de una encuesta nacional que explora la disponibilidad de equipos, indicacion y utilizacion de dicha tecnica, asi como la formacion y acreditacion de los profesionales responsables. Los hallazgos muestran que en Espana la ETE intraoperatoria es parte integral de los procedimientos cardiovasculares hoy en dia y en la mayor parte de los centros es realizada por anestesiologos altamente involucrados en este tipo de cirugias. A pesar de la ausencia de formacion estructurada en el curriculum formativo de nuestra especialidad, los anestesiologos adquieren las competencias mediante rotaciones especificas de corta duracion y un alto porcentaje de ellos ha obtenido la acreditacion oficial.

Transesophageal echocardiography (TEE) is an essential tool in the intraoperative and postoperative period of cardiac surgery with recently wide diffusion. We aimed to know the current situation of TEE in the field of cardiovascular anesthesiology in Spain through a national survey that explores the availability of equipment, indication and use of this technique as well as the training and accreditation of professionals involved. The findings show that in Spain intraoperative TEE is an integral part of cardiovascular procedures today and in most centers it is performed by anesthesiologists highly involved in this type of surgery. Despite the absence of structured training in the curriculum of our specialty, anesthesiologists acquire the skills through specific short-term rotations and a high percentage of them have obtained official accreditation.

Resumen: La ecocardiografía transesfofágica es una técnica semiinvasiva que permite una evaluación de la morfología y función cardiaca a tiempo real y que constituye, a día de hoy, un estándar de calidad en las intervenciones de cirugía cardiovascular. Se ha convertido en una herramienta fundamental tanto de monitorización como de diagnóstico en el perioperatorio que permite la correcta planificación quirúrgica y manejo farmacológico dirigido.El objetivo de este documento es dar respuesta de forma consensuada y avalada por la evidencia científica de cuándo y cómo debe hacerse la ecocardiografía transesfofágica intraoperatoria en cirugía cardiovascular, qué aplicaciones tiene en el intraoperatorio, quién debe realizarla y cómo debe transmitirse la información obtenida durante el estudio. Los autores han hecho una revisión sistemática de las guías internacionales, artículos de revisión y ensayos clínicos para dar respuesta a estas preguntas. Abstract: Transesophageal echocardiography is a semi-invasive technique that allows an evaluation of cardiac morphology and function in real time and it is a quality standard in cardiovascular surgery. It has become a fundamental tool for both monitoring and diagnosis in the intraoperative period that allows decide the correct surgical planning and pharmacological management.The goal of this document is to answer the questions of when and how the perioperative TEE should be performed in cardiovascular surgery, what are their applications in the intraoperative, who should perform it and how the information should be transmitted. The authors made a systematic review of international guidelines, review articles and clinical trials to answer by consensus to these questions.

To investigate the effect of an Enhanced Recovery After Surgery (ERAS) program on complications and length of stay (LOS) after radical cystectomy (RC) and to assess if the number and type of components of ERAS play a key role on the decrease of surgical morbidity. We analyzed the data of 277 patients prospectively recruited in 11 hospitals undergoing RC initially managed according to local practice (Group I) and later within an ERAS program (Group II). Two main outcomes were defined: 90-day complications rate and LOS. As secondary variables we studied 90-day mortality, 30-day readmission and transfusion rate. Patients in Group II had a higher use of ERAS measures (98.6%) than those in Group I (78.2%) (p

Introduction Cardiac surgery (CS) is associated with a significant use of blood products. The aim of this study was to evaluate the effect of red blood cells concentrates (RBC) transfusion on regional cerebral oxygen saturation (SrO2) in patients undergoing CS with additive EuroSCORE I > 6. Material and methods This is a prospective descriptive study. Patients with additive EuroSCORE I > 6 undergoing CS with extracorporeal circulation were included in the study. The demographic values, perioperative complications, hospital/ICU length of stay (LOS), as well as the preinduction baseline SrO2 values, the lowest SrO2 value during surgery, number of blood products transfused, hemoglobin (HB) and pre and postransfusional SrO2 values were recorded, and events of significant decrease in SrO2 below 20% of basal value or decrease below 50%. We considered responders those who had an increase post-transfusion SrO2 at least 20% of pre-transfusion value, an increase of standard deviation (7.9) or an increase up to basal SrO2. Results Data from 57 patients were collected. The average additive EuroSCORE I was 7.4 (SD 2.6) and the EuroSCORE II was 6.1 (SD 7.4). 52% were male. 35.1% of patients received intraoperative transfusion of at least one unit of RBC. The overall mortality was 8.7% (N = 5). During surgery 29.8% of the overall sample presented a decrease of more than 20% of baseline SrO2 or a value lower than 50%. Patients with a significant decrease in SrO2 presented a higher rate of perioperative complications (p = 0.04) and longer ICU-LOS 4.3 (SD 3.6) vs. 6.8 (SD 8.2) days (p = 0.01) and hospital LOS 10.1 (SD 3.1) vs. 14.2 (SD 9.4) days (p = 0.01). Pretransfusional HB was 7.4 (SD 0.8) mg/dl and postransfusional value was 8.4 (SD 0.8) (p = 0.00). Pretransfusional SrO2 was 59 (SD 8.6) and increased non- significantly after RBC transfusion to 61.1 (SD 7.9) (p = 0.1). Only 6 patients out of 21 could be considered responders. There were no significant differences in morbidity, mortality or LOS between responders and non-responders. Discussion In our population a non statistically significant increase in SrO2 was observed after RBC transfusion. When considering responders few patients were identified by SrO2. In conclusion SrO2 might not be reliable triger to decide transfusion.

Resumen Introduccion La cirugia cardiaca se asocia a un uso significativo de hemoderivados. El objetivo de este estudio fue evaluar el efecto de la transfusion sobre la saturacion regional de oxigeno cerebral (SrO2) en pacientes tratados mediante cirugia cardiaca con EuroSCORE I aditivo > 6. Material y metodos Estudio prospectivo observacional. Se incluyo en el estudio a los pacientes con EuroSCORE I aditivo > 6 tratados mediante cirugia cardiaca con circulacion extracorporea. Se recogieron los valores demograficos, complicaciones perioperatorias, estancias hospitalarias, asi como el valor de SrO2 basal preinduccion, el valor mas bajo de hemoglobina (Hb) registrado durante la cirugia, el valor de la Hb y la SrO2 pre y postransfusional, asi como la existencia de una caida significativa de mas del 20% del valor basal de la SrO2 o por debajo del 50%. Consideramos como respondedores a la transfusion aquellos que presentaron un aumento de la SrO2 postransfusion de al menos el 20% del valor previo, un aumento de la desviacion estandar (DE) (7,9) o un aumento hasta el nivel basal. Resultados Se recogieron los datos de 57 pacientes. El EuroSCORE I aditivo medio ± DE fue de 7,4 ± DE 2,6 y el EuroSCORE II fue de 6,1 ± DE 7,4. El 52% fueron varones. Se trasfundio al menos un concentrado de hematies al 35,1% de la muestra (20 pacientes). La SrO2 pretransfusional fue 59 ± DE 8,6 y aumento de forma no significativa tras la transfusion del primer CH (61,19 ± 7,9; p = 0,1). Un 29,8% de los pacientes presentaron durante la cirugia una disminucion de la SrO2 del 20% con respecto a su basal o un valor inferior al 50%. Los pacientes con una disminucion significativa de la SrO2 presentaron un mayor tasa de complicaciones perioperatorias (p = 0,04). La estancia en la Unidad de Cuidados Intensivos (UCI) fue mayor en los pacientes con una disminucion significativa de la SrO2 respecto a los que la no presentaron (6,8 ± 8,2 dias vs. 4,3 ± 3,6; p = 0,01) al igual que la estancia hospitalaria (14,2 ± 9,4 dias vs. 10,1 ± 3,1; p = 0,01). En nuestra muestra, 6 de los 21 pacientes fueron respondedores. No hubo diferencias significativas en la morbilidad o la mortalidad entre los respondedores y los no respondedores. Discusion En nuestra poblacion, se observo un aumento no significativo en la SrO2 tras la transfusion. Cuando se analizaron los respondedores a la transfusion por incrementos de SrO2, pocos pacientes fueron identificados como respondedores. En conclusion, la SrO2 podria no ser una herramienta que guie la transfusion en pacientes tratados mediante cirugia cardiaca con EuroSCORE I aditivo > 6.

Summary: Dorsal raphe (DR) serotonin neurons provide a major input to the ventral tegmental area (VTA). Here, we show that DR serotonin transporter (SERT) neurons establish both asymmetric and symmetric synapses on VTA dopamine neurons, but most of these synapses are asymmetric. Moreover, the DR-SERT terminals making asymmetric synapses on VTA dopamine neurons coexpress vesicular glutamate transporter 3 (VGluT3; transporter for accumulation of glutamate for its synaptic release), suggesting the excitatory nature of these synapses. VTA photoactivation of DR-SERT fibers promotes conditioned place preference, elicits excitatory currents on mesoaccumbens dopamine neurons, increases their firing, and evokes dopamine release in nucleus accumbens. These effects are blocked by VTA inactivation of glutamate and serotonin receptors, supporting the idea of glutamate release in VTA from dual DR SERT-VGluT3 inputs. Our findings suggest a path-specific input from DR serotonergic neurons to VTA that promotes reward by the release of glutamate and activation of mesoaccumbens dopamine neurons. : Wang et al. identify the ultrastructural and molecular characteristics of synaptic connectivity between DR serotonin neurons and VTA dopamine neurons and determined the role of these connections in behavior. Their results indicate that the DR→VTA serotonergic neurons promote reward by the co-release of glutamate and activation of mesoaccumbens dopamine neurons. Keywords: dorsal raphe nucleus, ventral tegmental area, serotonin, VGluT3, reward

The ventral tegmental area (VTA) contains dopamine neurons intermixed with GABA-releasing (expressing vesicular GABA transporter, VGaT), glutamate-releasing (expressing vesicular glutamate transporter, VGluT2), and co-releasing (co-expressing VGaT and VGluT2) neurons. By delivering INTRSECT viral vectors into VTA of double vglut2-Cre/vgat-Flp transgenic mice, we targeted specific VTA cell populations for ex vivo recordings. We found that VGluT2+ VGaT− and VGluT2+ VGaT+ neurons on average had relatively hyperpolarized resting membrane voltage, greater rheobase, and lower spontaneous firing frequency compared to VGluT2− VGaT+ neurons, suggesting that VTA glutamate-releasing and glutamate-GABA co-releasing neurons require stronger excitatory drive to fire than GABA-releasing neurons. In addition, we detected expression of Oprm1mRNA (encoding μ opioid receptors, MOR) in VGluT2+ VGaT− and VGluT2− VGaT+ neurons, and their hyperpolarization by the MOR agonist DAMGO. Collectively, we demonstrate the utility of the double transgenic mouse to access VTA glutamate, glutamate-GABA and GABA neurons, and show some electrophysiological heterogeneity among them.Impact StatementSome physiological properties of VTA glutamate-releasing and glutamate-GABA co-releasing neurons are distinct from those of VTA GABA-releasing neurons. μ-opioid receptor activation hyperpolarizes some VTA glutamate-releasing and some GABA-releasing neurons.

Background: Shared risk factors of type 2 diabetes mellitus (T2DM) between parents at risk and their children, such as low physical activity levels, should be addressed to prevent the development of the disease. The aim of this study was to determine the association of objectively measured step counts per day between parents at risk of developing T2DM and their 6- to 10-year-old children. Methods: The baseline data from the Feel4Diabetes study were analyzed. Dyads of children and one parent (n = 250, 54.4% girls and 77.6% mothers) from Belgium were included. Step counts per day during 5 consecutive days from parents and their children were objectively measured with ActiGraph accelerometers. Results: Adjusted linear regression models indicated that parents’ and children’s step counts were significantly associated during all days (β = 0.245), weekdays (β = 0.205), and weekend days (β = 0.316) (P ≤ .002 in all cases). Specifically, mother–daughter associations during all days and weekend days and father–son step counts during weekdays and when considering all days were significant. Conclusion: There is a positive association between step counts from adults at risk of developing T2DM and their children, especially in the mother–daughter and father–son dyads. © 2021 Human Kinetics, Inc.

Resumen: La vía clínica de recuperación intensificada en cirugía cardiaca (RICC) pretende identificar, difundir y favorecer la implementación de las mejores actuaciones basadas en la evidencia científica para disminuir la variabilidad en la práctica clínica. La puesta en marcha de estas prácticas en el proceso clínico global favorecerá la obtención de mejores resultados, acortamiento de estancias hospitalarias y en la Unidad de Cuidados Críticos, lo que permitirá una reducción de costes y una mayor eficiencia. Tras realizar una revisión sistemática en cada uno de los puntos del proceso perioperatorio en cirugía cardiaca, se han redactado recomendaciones basadas en la mejor evidencia científica disponible en la actualidad con el consenso de las sociedades científicas implicadas. Abstract: The ERAS guidelines are intended to identify, disseminate and promote the implementation of the best, scientific evidence-based actions to decrease variability in clinical practice. The implementation of these practices in the global clinical process will promote better outcomes and the shortening of hospital and critical care unit stays, thereby resulting in a reduction in costs and in greater efficiency. After completing a systematic review at each of the points of the perioperative process in cardiac surgery, recommendations have been developed based on the best scientific evidence currently available with the consensus of the scientific societies involved.

Sugar sap from Nipa (Nypa fruiticans) palm is one of the promising sustainable feedstocks for ethanol production. There are different stages and processes needed for the sap to produce ethanol particularly: collection, fermentation, and distillation. In order to produce high ethanol concentration and yield, each stage or process needs to be optimized and improved as such, this study optimized the flow rate and temperature of the cooling system of a 10 L full electric Reflux distiller for the production of a fuel grade (95%) bioethanol from nipa sap. The optimal power density for the 10 L full electric reflux distiller was also determined. Optimizing these parameters improved the concentration of the ethanol, ethanol yield and also decreased the operational cost of the 10 L full electric reflux distiller. First step was to determine the power density required for the 10 L Lab-Scale Distiller through experiment using different power density. After identifying the power density, multiple trials were performed with 2 protocols being the continuous method and recirculating method of the cooling system. Results showed that a flow rate of 0.77 L/min, a 27 °C cooling liquid temperature and a 100W/m3 power density were obtained. An increase of 154.2% in volume of consistent 95% concentration yield was observed. Also, there was a significant increase in the yield. Continuous method was faster by an average of 26 minutes compared to the recirculating method.

[ES] La ecocardiografía transesfofágica es una técnica semiinvasiva que permite una evaluación de la morfología y función cardiaca a tiempo real y que constituye, a día de hoy, un estándar de calidad en las intervenciones de cirugía cardiovascular. Se ha convertido en una herramienta fundamental tanto de monitorización como de diagnóstico en el perioperatorio que permite la correcta planificación quirúrgica y manejo farmacológico dirigido. El objetivo de este documento es dar respuesta de forma consensuada y avalada por la evidencia científica de cuándo y cómo debe hacerse la ecocardiografía transesfofágica intraoperatoria en cirugía cardiovascular, qué aplicaciones tiene en el intraoperatorio, quién debe realizarla y cómo debe transmitirse la información obtenida durante el estudio. Los autores han hecho una revisión sistemática de las guías internacionales, artículos de revisión y ensayos clínicos para dar respuesta a estas preguntas., [EN] Transesophageal echocardiography is a semi-invasive technique that allows an evaluation of cardiac morphology and function in real time and it is a quality standard in cardiovascular surgery. It has become a fundamental tool for both monitoring and diagnosis in the intraoperative period that allows decide the correct surgical planning and pharmacological management. The goal of this document is to answer the questions of when and how the perioperative TEE should be performed in cardiovascular surgery, what are their applications in the intraoperative, who should perform it and how the information should be transmitted. The authors made a systematic review of international guidelines, review articles and clinical trials to answer by consensus to these questions.

OBJECTIVES Tranexamic acid is used to prevent hyperfibrinolysis and reduce postoperative bleeding and blood transfusions in on-pump cardiac surgery. We evaluate the efficacy of low or high dose tranexamic acid in a prospective cohort study conducted in Valencia. MATERIALS AND METHODS A total of 427 patients were recruited between January 2019 and January 2020, 207 in the Hospital General Universitario (low dose [LD]) and 220 in the Hospital Universitario y Politecnico La Fe (high dose [HD] and intermediate dose [ID]). We recorded the presence of hyperfibrinolysis on rotational thromboelastometry, intra- and postoperative administration of blood products, chest tube output within the first 12 h, and incidence of convulsions. Univariate and multivariate comparisons were performed. Univariate analysis of all categories was performed after propensity score matching between LD and HD and between LD and ID. RESULTS There were no statistically significant differences in: appearance of hyperfibrinolysis, administration of blood products, postoperative chest tube output within the first 12 h, or occurrence of convulsions. Group LD received less fibrinogen than group HD (P = .014) and ID (P = .040) but more fresh frozen plasma than group ID (P = .0002). CONCLUSIONS Administration of low-dose tranexamic acid is as effective as higher doses in hyperfibrinolysis prophylaxis and the prevention of postoperative bleeding in cardiac surgery.

Background: The study aimed to investigate the effectiveness of the European Feel4Diabetes intervention, promoting a healthy lifestyle, on physical activity and its correlates among families at risk for type 2 diabetes mellitus (based on the Finnish Diabetes Risk Score) in Belgium. Methods: The Feel4Diabetes intervention involved three components: family, school and community component, with the family component consisting of 6 counseling sessions for families at risk. Main outcomes were objectively measured physical activity levels and its subjectively measured correlates. The final sample consisted of 454 parents (mean age 39.4 years; 72.0% women) and 444 children (mean age 8.0 years; 50.1% girls). Multilevel repeated measures analyses were performed to assess intervention effectiveness after 1 year. Results: In parents, there was no significant intervention effect. In children, there were only significant negative effects for moderate to vigorous physical activity (p = 0.05; ηp2 = 0.008) and steps (p = 0.03; ηp2 = 0.006%) on weekdays, with physical activity decreasing (more) in the intervention group. Conclusions: The F4D-intervention lacks effectiveness on high-risk families' physical activity and its correlates in Belgium. This could partially be explained by low attendance rates and a large drop-out. To reach vulnerable populations, future interventions should invest in more appropriate recruitment (e.g. more face-to-face contact) and more bottom-up development of the intervention (i.e. co-creation of the intervention with the target group). Trial registration: The Feel4Diabetes-study was prospectively registered at clinicaltrials.gov as NCT02393872 on 20 March 2015. © 2020 The Author(s).

Background: The aim of this paper is to present the development of the Feel4Diabetes Healthy Diet Score and to evaluate its clinical validity. Methods: Study population consisted of 3268 adults (63% women) from high diabetes risk families living in 6 European countries. Participants filled in questionnaires at baseline and after 1 year, reflecting the dietary goals of the Feel4Diabetes intervention. Based on these questions the Healthy Diet Score was constructed, consisting of the following components: breakfast, vegetables, fruit and berries, sugary drinks, whole-grain cereals, nuts and seeds, low-fat dairy products, oils and fats, red meat, sweet snacks, salty snacks, and family meals. Maximum score for each component was set based on its estimated relative importance regarding T2DM risk, higher score indicating better quality of diet. Clinical measurements included height, weight, waist circumference, heart rate, blood pressure, and fasting blood sampling, with analyses of glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides. Analysis of (co) variance was used to compare the Healthy Diet Score and its components between countries and sexes using baseline data, and to test differences in clinical characteristics between score categories, adjusted for age, sex and country. Pearson's correlations were used to study the association between changes from baseline to year 1 in the Healthy Diet Score and clinical markers. To estimate reproducibility, Pearson's correlations were studied between baseline and 1 year score, within the control group only. Results: The mean total score was 52.8 ± 12.8 among women and 46.6 ± 12.8 among men (p < 0.001). The total score and its components differed between countries. The change in the Healthy Diet Score was significantly correlated with changes in BMI, waist circumference, and total and LDL cholesterol. The Healthy Diet Score as well as its components at baseline were significantly correlated with the values at year 1, in the control group participants. Conclusion: The Feel4Diabetes Healthy Diet Score is a reproducible method to capture the dietary information collected with the Feel4Diabetes questionnaire and measure the level of and changes in the adherence to the dietary goals of the intervention. It gives a simple parameter that associates with clinical risk factors in a meaningful manner. Trial registration: Clinicaltrials.gov NCT02393872. Registered March 20, 2015. © 2020 The Author(s).

Background: Although there are many interventions targeting childhood obesity prevention, only few have demonstrated positive results. The current review aimed to gather and evaluate available school-based intervention studies with family involvement targeting dietary, physical activity and sedentary behaviors among primary schoolchildren and their families, in order to identify the most effective strategies. Methods: Studies published between 2000 and January 2015 were retrieved from scientific electronic databases and grey literature. The databases used included MEDLINE/PubMed, Web-of-Science, CINAHL and Scopus. Included studies had to be experimental controlled studies and had duration over 1 school year, had family involvement, combined PA and dietary behaviors and were implemented in school setting. A complementary search was executed to update the review to cover the period from February 2015 to January 2019. Results: From the studies examined (n = 425), 27 intervention programs (33 publications) fulfilled the inclusion criteria. Among these, 15 presented significant effect on weight status and/ or overweight/ obesity or clinical indices, 3 presented significant effect on most energy balance-related behaviors (EBRBs) while 9 presented significant effect on some/few EBRBs or determinants. Strategies implemented in effective interventions were: teachers acting as role-models and being actively involved in the delivery of the intervention, school policies supporting the availability of healthy food and beverage choices and limiting unhealthy snacks, changes in the schoolyard, in the recess rules and in the physical education classes to increase physical activity, and involving parents in the intervention via assignments, meetings, informative material and encouraging them to improve the home environment. Use of incentives for children, social marketing techniques, collaboration with local stakeholders were found to increase effectiveness. Programs that focused only on educational sessions and material for parents, without promoting relevant environmental and policy changes, were found to be less effective. Cultural adaptations have been suggested to increase the intervention's acceptance in specific or vulnerable population groups. Conclusions: Several effective strategies were identified in the reviewed programs. Outcomes of the current review were taken into account in developing the Feel4Diabetes-intervention and summed up as recommendations in the current work in order to facilitate other researchers designing similar childhood obesity prevention initiatives. © 2020 The Author(s).

Cannabinoid receptor 1 (CB(1)) is a G-protein–coupled receptor that is abundant in the central nervous system. It binds several compounds in its orthosteric site, including the endocannabinoids, arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol, and the plant-derived Δ(9)-tetrahydrocannabinol, one of the main psychoactive components of marijuana. It primarily couples to G(i/o) proteins to inhibit adenylate cyclase activity and typically induces downstream signaling that is G(i)-dependent. Since this receptor is implicated in several maladies, such as obesity, pain, and neurodegenerative disorders, there is interest in developing therapeutics that selectively target this receptor. Allosteric modulators of CB(1) offer one new approach that has tremendous therapeutic potential. Here, we reveal receptor- and cellular-level properties consistent with receptor activation by a series of pyrimidinyl biphenylureas (LDK1285, LDK1288, LDK1305, and PSNCBAM1), including promoting binding of the agonist CP55940 with positive cooperativity and inhibiting binding of the inverse agonist SR141716A with negative cooperativity, demonstrated via radioligand binding studies. Consistent with these findings, the allosteric modulators induced cellular internalization of the receptor and recruitment of β-arrestin 2 in human embryonic kidney cell line 293 cells monitored with confocal and total internal reflective fluorescence microscopy, respectively. These allosteric modulators, however, caused G-protein–independent but β-arrestin 1–dependent phosphorylation of the downstream kinases extracellular signal-regulated kinase 1/2, mitogen-activated protein kinase, and Src, shown by immunoblotting studies. These results are consistent with the involvement of β-arrestin and suggest that these allosteric modulators induce biased signaling.

Introduction Acute renal failure (ARF) after cardiac surgery is a risk factor associated with mortality and use of resources. Some studies have reported beneficial effects of pulsatile flow on cardiopulmonary bypass (CPB) on renal function. The aim of this study is to describe the echographic morphology of the renal arterial wave modifying the parameters of pulsatile CPB. Material and method Descriptive study was performed on 10 patients without previous AFR and undergoing cardiac surgery with CPB. Pre-, intra- and post-surgery renal ultrasound was performed. During pulsatile CPB, the amplitude and the baseline flow were modified. Recordings of pulsed Doppler in intrarenal arteries were obtained by measuring maximum systolic velocity, minimum diastolic velocity, resistance index (RI) and acceleration time (AT). Results Statistical differences were found in ultrasounds pre-CPB between A50F50 modality (p = 0.013), A50F30 (p = 0.013) and A60F50 (p = 0.003). No statistically significance was found with A30F30 modality (p = 0.125). Conclusions The decrease in the amplitude and the baseline flow of pulsatility during CPB shows a renal ultrasound morphology that is more similar to the physiological one. Subsequent studies using these characteristics during pulsatile CPB could thus show perfusion over the ARF that occurs after cardiac surgery.

Resumen Introduccion El fracaso renal agudo (FRA) tras la cirugia cardiaca es un factor de riesgo asociado a mortalidad y consumo de recursos. Algunos estudios encuentran efectos beneficiosos del flujo pulsatil en la circulacion extracorporea (CEC) sobre la funcion renal. El objetivo de este estudio es describir la morfologia ecografica de la onda arterial renal modificando los parametros de la CEC pulsatil. Material y metodo Estudio descriptivo de 10 pacientes intervenidos mediante cirugia cardiaca con CEC sin FRA previo. Se realizo ecografia renal pre-, intra- y poscirugia. Durante la CEC pulsatil se modificaron la amplitud y el flujo base. Se obtuvieron registros de Doppler pulsado en arterias intrarrenales, se midio la velocidad maxima sistolica y la velocidad minima diastolica, el indice de resistencia (IR) y el tiempo de aceleracion (TAcel). Resultados La ecografia previa a la CEC (pre-CEC) muestra que hay diferencias significativas cuando se compara con los valores obtenidos en la modalidad A50F50 (p = 0,013), A50F30 (p = 0,013) y A60F50 (p = 0,003). No las hay para la modalidad A30F30 (p = 0,125). Conclusiones La disminucion de la amplitud y del flujo base de la pulsatilidad durante la CEC permite obtener una morfologia ecografica renal mas parecida a la fisiologica. Estudios posteriores utilizando estas caracteristicas durante la CEC pulsatil podrian mostrar la repercusion de este modo de perfusion sobre el FRA que se produce tras la cirugia cardiaca.

Introduction Laparoscopic radical cystectomy with lymphadenectomy and urinary diversion is an increasingly widespread operation. Studies are needed to support the oncological effectiveness and safety of this minimally invasive approach. Patients and methods A non-randomized, comparative prospective study between open radical cystectomy (ORC) and laparoscopic radical cystectomy (LRC) was conducted in a university hospital. The main objective was to compare cancer-specific survival. The secondary objective was to compare the surgical results and complications according to the Clavien–Dindo scale. Results We treated 156 patients with high-grade invasive bladder cancer with either ORC ( n = 70) or LRC ( n = 86). The mean follow-up was 33.5 ± 23.8 (range 12–96) months. The mean age was 66.9 + 9.4 years, and the male to female ratio was 19:1. Both groups were equivalent in age, stage, positive lymph nodes, in situ carcinoma, preoperative obstructive uropathy, adjuvant chemotherapy and type of urinary diversion. There were no differences between the groups in terms of cancer-specific survival (log-rank; p = 0.71). The histopathology stage was the only independent variable that predicted the prognosis. The hospital stay ( p = 0.01) and operative transfusion rates ( p = 0.002) were less for LRC. The duration of the surgery was greater for LRC ( p p = 0.62) or major complications ( p = 0.69). The risk of evisceration ( p = 0.02), surgical wound infection ( p = 0.005) and pneumonia ( p = 0.017) was greater for ORC. The risk of rectal lesion ( p = 0.017) and urethrorectal fistulae ( p = 0.065) was greater for LRC. Conclusion LRC is an equivalent treatment to ORC in terms of oncological efficacy and is advantageous in terms of transfusion rates and hospital stays but not in terms of operating room time and overall safety. Studies are needed to better define the specific safety profile for each approach.

Resumen Introduccion El objetivo de este estudio es describir nuestra experiencia en la cirugia de revascularizacion coronaria aislada en pacientes mayores de 80 anos e identificar los riesgos especificos y predictores de mortalidad precoz. Material y metodos Entre enero de 1999 y junio de 2013, 3.097 pacientes fueron sometidos a cirugia de revascularizacion coronaria aislada. Se analizaron los pacientes mayores de 80 anos de edad. Se realizo una regresion mutivariante de Cox para predictores de mortalidad. Resultados Se identificaron 99 pacientes mayores de 80 anos (grupo-80; edad media 82 ± 3,5 anos) y 2.957 menores de 80 anos (grupo control; edad media 64,2 ± 9,7 anos). El EuroSCORE aditivo fue 8,4 ± 4,8 y 4,6 ± 4,6 (p 80 anos vs. Conclusion La cirugia de revascularizacion coronaria aislada se realiza preferentemente en pacientes mayores de 80 anos sin CEC. Presentan una mayor incidencia de complicaciones cardiovasculares, reintervenciones por sangrado en el postoperatorio inmediato y una mortalidad mas elevada.

Cardiac surgery (CS) is associated with a significant use of blood products. The aim of this study was to evaluate the effect of red blood cells concentrates (RBC) transfusion on regional cerebral oxygen saturation (SrOThis is a prospective descriptive study. Patients with additive EuroSCORE I6 undergoing CS with extracorporeal circulation were included in the study. The demographic values, perioperative complications, hospital/ICU length of stay (LOS), as well as the preinduction baseline SrOData from 57 patients were collected. The average additive EuroSCORE I was 7.4 (SD 2.6) and the EuroSCORE II was 6.1 (SD 7.4). 52% were male. 35.1% of patients received intraoperative transfusion of at least one unit of RBC. The overall mortality was 8.7% (N = 5). During surgery 29.8% of the overall sample presented a decrease of more than 20% of baseline SrO2 or a value lower than 50%. Patients with a significant decrease in SrO2 presented a higher rate of perioperative complications (P=0.04) and longer ICU-LOS 4.3 (SD 3.6) vs. 6.8 (SD 8.2) days (P=0.01) and hospital LOS 10.1 (SD 3.1) vs. 14.2 (SD 9.4) days (P=0.01). Pretransfusional HB was 7.4 (SD 0.8) mg/dl and postransfusional value was 8.4 (SD 0.8) (P =0.00). Pretransfusional SrO2 was 59 (SD 8.6) and increased non- significantly after RBC transfusion to 61.1 (SD 7.9) (P=0.1). Only 6 patients out of 21 could be considered responders. There were no significant differences in morbidity, mortality or LOS between responders and non-responders.In our population a non statistically significant increase in SrO2 was observed after RBC transfusion. When considering responders few patients were identified by SrO

The correct affiliation of Sabrina Lo Brutto is shown in this paper. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

The definition of recurrent pregnancy loss varies according different authors and consensus: the American Society for Reproductive Medicine (ASRM) defines RPL when two or more pregnancy losses occur, and the European Society of Human Reproduction and Embryology (ESHRE) defines it as three or more pregnancy losses, not necessarily intrauterine. To this day, there is no uniform approach that serves as a guide in the diagnosis and treatment of this condition; this is why, in up to 50% of the cases of RPL, it will not be possible to identify the specific etiology.To report on the recurrent pregnancy loss, in order to harmonize concepts and suggest a diagnosis and treatment for this condition approach.The search strategy included, but was not limited to keywords like: recurrent abortion, infertility, habitual abortion, primary antiphospholipid syndrome, lupus anticoagulant, anti-cardiolipin antibodies and anti B2 glycoprotein I.

Introducción: La cistectomía radical laparoscópica con linfadenectomía y derivación urinaria es una cirugía de empleo creciente. Se necesitan estudios que avalen la efectividad oncológica y la seguridad de este abordaje mínimamente invasivo. Pacientes y métodos: Estudio prospectivo comparativo no aleatorizado entre cistectomía radical abierta (CRA) y laparoscópica (CRL) llevado a cabo en un hospital universitario. El objetivo principal fue comparar la supervivencia cáncer-específica, y el objetivo secundario comparar resultados operatorios y complicaciones según la escala Clavien-Dindo. Resultados: Ciento cincuenta y seis pacientes con cáncer vesical invasivo de alto grado fueron tratados mediante CRA (n = 70) o CRL (n = 86). El seguimiento medio fue 33,5 ± 23,8 (rango 12-96) meses. La edad media fue 66,9 + 9,4 años y la proporción hombre/mujer 19:1. Ambos grupos fueron equivalentes en edad, estadio, ganglios positivos, carcinoma in situ, uropatía obstructiva preoperatoria, quimioterapia adyuvante y tipo de derivación urinaria. No hubo diferencias entre grupos en supervivencia cáncer-específica (log-rank; p = 0,71). El estadio histopatológico fue la única variable independiente predictiva de pronóstico. La estancia hospitalaria (p = 0,01) y la tasa de transfusión operatoria (p = 0,002) fueron menores para CRL. La duración de la cirugía fue mayor para CRL (p < 0,001). No hubo diferencias en la tasa de complicaciones totales (p = 0,62) ni complicaciones mayores (p = 0,69). El riesgo de evisceración (p = 0,02), infección de herida quirúrgica (p = 0,005) y neumonía (p = 0,017) fue mayor en CRA. El riesgo de lesión rectal (p = 0,017) y fístula uretrorrectal (p = 0,065) fue mayor en CRL. Conclusión: La CRL es un tratamiento equivalente a la CRA en términos de eficacia oncológica, y ventajoso respecto a tasa de transfusión y estancia hospitalaria, pero no respecto a la ocupación de quirófano o a la seguridad global. Se necesitan estudios que definan mejor el perfil de seguridad específico de cada abordaje. Introduction: Laparoscopic radical cystectomy with lymphadenectomy and urinary diversion is an increasingly widespread operation. Studies are needed to support the oncological effectiveness and safety of this minimally invasive approach. Patients and methods: A nonrandomised, comparative prospective study between open radical cystectomy (ORC) and laparoscopic radical cystectomy (LRC) was conducted in a university hospital. The main objective was to compare cancer-specific survival. The secondary objective was to compare the surgical results and complications according to the Clavien-Dindo scale. Results: We treated 156 patients with high-grade invasive bladder cancer with either ORC (n = 70) or LRC (n = 86). The mean follow-up was 33.5 ± 23.8 (range 12-96) months. The mean age was 66.9 + 9.4 years, and the male to female ratio was 19:1. Both groups were equivalent in age, stage, positive lymph nodes, in situ carcinoma, preoperative obstructive uropathy, adjuvant chemotherapy and type of urinary diversion. There were no differences between the groups in terms of cancer-specific survival (log-rank; P = .71). The histopathology stage was the only independent variable that predicted the prognosis. The hospital stay (P = .01) and operative transfusion rates (P = .002) were less for LRC. The duration of the surgery was greater for LRC (P

The use of weak polyelectrolytes in multilayer polymer systems provides a means of altering the physicochemical properties of these thin films. Previously, we have examined the limits of the polyanions by incorporating the pseudo-polyelectrolytes (pPE's), poly(4-vinylphenol) (PVPh) and poly[5-(2-trifluoromethyl-1,1,1-trifluoro-2-hydroxypropyl)-2-norbornene] (PNBHFA). These pPE's, although being polyacids, should have p K a values in the basic versus acidic pH range. In order to determine the p K a(app) value of these polymers, once multilayered onto Snowtex silica particles with the weak polyelectrolyte, poly(allylamine hydrochloride) (PAH), we employed zeta potential. PVPh demonstrated p K a(app) values ranging from 10.55 to 11.08 which varied based upon assembly pH conditions as well as layer number. PAH yielded p K a(app) values ranging between 9.81 and 10.99 when multilayered with PVPh and 9.91–11.04 when partnered with PNBHFA. However, from our study it would appear that PNBHFA does not interact with PAH electrostatically, but rather via H-bonding, and therefore should actually not be classified as a pPE.

ResumenLa cirugía cardiaca con circulación extracorpórea (CEC) se asocia con un aumento de sangrado postoperatorio, consumo de productos hemáticos y número de reexploraciones quirúrgicas. Actualmente, del 50% de los pacientes de cirugía cardiaca transfundidos, el 20% tiene un sangrado significativo y el 5% requiere reoperación por sangrado postoperatorio. Este aumento de hemoderivados aumenta la morbimortalidad, la estancia hospitalaria y los costes sanitarios. Las causas de la coagulopatía después de la CEC son multifactoriales: la hemodilución, la exposición de la sangre a los circuitos de la CEC, la destrucción de las plaquetas y la activación de la trombina. Las directrices de las sociedades científicas americanas y europeas recomiendan el uso de ácido tranexámico (AT) para reducir la hemorragia perioperatoria en la cirugía cardiaca. El AT ahorra un promedio de 300ml de sangre con una reducción relativa del 32% al recibir una transfusión. Las intervenciones con CEC sin el uso de fármacos antifibrinolíticos se caracteriza por un aumento de la pérdida de sangre, reoperaciones y la transfusión de productos sanguíneos en comparación con otras intervenciones en donde se han utilizado antifibrinolíticos. El principal problema con el uso de AT se encuentra en los muchos patrones y diferentes dosis de administración, que varían de un artículo a otro. El objetivo de este artículo es alertar sobre el uso de altas dosis de AT y sus consecuencias, según las últimas recomendaciones de la literatura al respecto.AbstractCardiac surgery with cardiopulmonary bypass (CPB) is associated with increased postoperative bleeding, blood product consumption, and the number of surgical re-explorations. Currently, of the 50% of transfused patients from cardiac surgery, 20% have significant bleeding, and 5% required reoperation for postoperative bleeding. This increased consumption of blood increases morbidity, mortality, hospital stay, and healthcare costs. The causes of coagulopathy after CPB are multifactorial: hemodilution, blood exposure to CPB circuits, destruction of platelets, and thrombin activation. The guidelines of the American and European scientific societies recommend the use of tranexamic acid (TA) to reduce perioperative bleeding in cardiac surgery. TA saves an average of 300ml of blood, with a relative reduction of 32% receiving transfusion. CS interventions with CPB carried out without using any antifibrinolytic drug is characterized by increased blood loss, increased reoperations for bleeding, and increased transfusion and blood products, when compared to other interventions where antifibrinolytic were used. The main problem with the use of TA lies in the many administration patterns and different doses,, which vary from one article to another. The aim of this article is to alert on the use of high doses of TA and its consequences according to the latest recommendations in the literature.

Resumen Objetivo Analisis de los resultados obtenidos mediante tecnica de reimplantacion ureteral laparoendoscopica por puerto unico (LESS) transumbilical con plataforma de puerto unico reutilizable. Material y metodo Se presenta la casuistica de 5 pacientes sometidos a reimplantacion ureteral LESS. Se describe la tecnica quirurgica empleada con plataforma de puerto unico KeyPort ® de colocacion umbilical y puerto accesorio de 3,5 mm en la fosa iliaca, a traves del cual se emplea material de minilaparoscopia que facilita la diseccion, aspiracion y sutura. Se presentan los resultados operatorios y postoperatorios obtenidos. La mediana de seguimiento en el momento del analisis fue de 11 ± 14 meses. Resultados La mediana de edad de los pacientes fue 49 ± 34 anos y la proporcion hombre/mujer 1:1,5. En todos los casos la reimplantacion fue izquierda. La etiologia fue secundaria a estenosis en 4 casos (3 iatrogenica y una debida a endometriosis pelvica) y en el caso restante se realizo tras escision de ureterocele tipo adulto sintomatico. En todos los casos se dejo sonda vesical por un tiempo de 7 ± 3 d y cateter ureteral doble-J 30 ± 15 d. No hubo reconversion a cirugia laparoscopica convencional ni abierta en ningun caso, y la duracion de la intervencion fue 145 ± 60 min con un sangrado intraoperatorio de 100 ± 75 cc. No se preciso transfusion ni analgesia al alta. No hubo complicaciones postoperatorias menores ni mayores y el tiempo de hospitalizacion fue 2 ± 0,5 d. Ningun paciente presento reestenosis ni empeoramiento de la funcion renal. Conclusiones La tecnica de ureteroneocistosotomia laparoendoscopica a traves de puerto unico transumbilical constituye una alternativa segura en centros con experiencia en este abordaje, con resultados equiparables a la laparoscopia convencional y excelente resultado cosmetico a muy bajo coste debido al caracter reutilizable del dispositivo.

Objective To analyze the outcomes of umbilical laparoendoscopic single-site (LESS) ureteral reimplantation using a reusable single-port platform. Materials and method The casuistic of LESS ureteral reimplantation in 5 patients is presented. The surgical technique using KeyPort system (reusable umbilical single-site platform) is described. Dissection, suctioning and suturing by minilaparoscopy through 3.5 mm accessory port in the iliac fossa are performed. Operative and postoperative outcomes are presented. The median follow-up at time of analysis was 11 ± 14 months. Results The median age of patients was 49 ± 34 years; male-female ratio was 1:1.15. Left surgery was carried out in all cases. In 4 patients, the etiology was secondary to stenosis (3 iatrogenic and 1 pelvic endometriosis). In the remaining case, the procedure was performed after excision of a symptomatic adult ureterocele. In all cases, bladder catheter and double-J ureteral catheter were inserted for 7 ± 3 and 30 ± 15 days and then removed. No conversion to convectional laparoscopic or open surgery occurred. The surgery time was 145 ± 60 min, and intraoperative bleeding was 100 ± 75 cc. Neither transfusion nor high analgesia was necessary. No postoperative complications, minor or major, have been reported. Hospital stay was 2 ± 0.5 days. In any patient, restenosis or worsening of renal function occurred. Conclusions In experimented centers, transumbilical laparoendoscopic single-site ureteroneocystostomy is a safe alternative with comparable results to conventional laparoscopy and an excellent cosmetic result at low cost thanks to device reuse.

Objective Probably, laparoscopic radical cystectomy with ileal neobladder and neovesicourethral anastomosis is one of the most complex procedures in minimally invasive surgery. Materials and methods Prospective study carried out in 72 patients surgically treated for invasive bladder neoplasia between January 2008 and October 2013. Patients underwent radical cystectomy with ileal neobladder (open approach in 33 patients and laparoscopic approach in 39). The study assessed comparatively surgical outcomes, continence rate and postoperative complications. Results Mean age was 63.5 ± 9 years (64.3 open vs. 62.7 laparoscopic, p = 0.46), mean surgery time 323.6 ± 78.7 minutes (321.3 vs. 326.5, p = 0.77), average hospital stay 14.8 days ± 8.1 (16.2 vs. 13.6, p = 0.2), transfusion rate 40.3% (66.7% vs. 17.9%, p

Resumen Objetivo La cistectomia radical laparoscopica con neovejiga ileal y anastomosis neovesicouretral realizada por laparoscopia posiblemente sea uno de los procedimientos mas complejos de la cirugia minimamente invasiva. Material y metodos Estudio prospectivo realizado entre enero de 2008 y octubre de 2013 con 72 pacientes afectos de neoplasia vesical infiltrante, intervenidos mediante cistectomia radical con neovejiga ileal (33 mediante tecnica abierta y 39 laparoscopica). Evaluamos de forma comparativa los resultados quirurgicos, la tasa de continencia y las complicaciones postoperatorias. Resultados La edad media fue 63,5 ± 9 anos (64,3 abierta vs. 62,7 laparoscopica, p = 0,46), el tiempo medio quirurgico 323,6 ± 78,7 min (321,3 vs. 326,5, p = 0,77), la estancia media 14,8 ± 8,1 dias (16,2 vs. 13,6, p = 0,2), la tasa de transfusion 40,3% (66,7% vs. 17,9%, p Conclusion En nuestra experiencia la tasa de transfusion, el numero y severidad de complicaciones es menor en la cistectomia radical con neovejiga realizada mediante abordaje laparoscopico, sin claro impacto en el tiempo quirurgico y en la estancia hospitalaria. La tasa de continencia de los pacientes intervenidos mediante abordaje laparoscopico es inferior, aunque sin alcanzar significacion estadistica.

Background and goal of study Postoperative myocardial infarction is a serious and frequent complication of cardiac surgery. Nonetheless, diagnosis in this context is occasionally challenging. We sought to evaluate the kinetics and diagnostic accuracy of the new biomarker “heart-type fatty acid-binding protein” (h-FABP) in the early detection of myocardial injury in patients undergoing off-pump coronary artery bypass grafting, compared with classical biomarkers. Materials and methods A prospective study was conducted on 17 consecutive patients who underwent off-pump coronary artery bypass grafting during a 2-month period. Blood samples were drawn for measurement of myocardial ischemic injury biomarkers (h-FABP, troponin, creatine kinase [CK] and CK-MB), at baseline (T1), immediate post-coronary artery bypass grafting (T2), on ICU admission (T3), and after 4 (T4), 8 (T5), 24 (T6) and 48 h (T7). Perioperative ischemic complications, defined according to electrocardiographic, echocardiographic and hemodynamic criteria, were recorded. Results Earlier peak biochemical marker plasma values occurred at T4 with troponin (2.9 ± 5.2 ng/mL), and at T5 with h-FABP (37.9 ± 55.5 ng/mL). Maximum values of CK and CK-MB occurred later, both in T6 (741 ± 779 and 37 ± 51 U/L, respectively). The optimized cut-off obtained for h-FABP was 19 ng/mL, providing a sensitivity and specificity of 77 and 75%, respectively, for diagnosis of perioperative ischemic injury, with an area under the ROC curve for h-FABP of 0.83 (95% CI 0.6–1.0) vs. 0.63 (95% CI 0.33–0.83) for troponin. This cut-off value for h-FABP is reached on average at T2 (mean value of h-FABP at T2: 18.9 ± 21.5 ng/mL). Conclusion This is the first study evaluating the kinetics of h-FABP biomarker in perioperative off-pump coronary artery bypass grafting, and the cut-off value established could help to extend earlier detection of myocardial ischemia in this context.

Acute renal failure (ARF) after cardiac surgery is a risk factor associated with mortality and use of resources. Some studies have reported beneficial effects of pulsatile flow on cardiopulmonary bypass (CPB) on renal function. The aim of this study is to describe the echographic morphology of the renal arterial wave modifying the parameters of pulsatile CPB.Descriptive study was performed on 10 patients without previous AFR and undergoing cardiac surgery with CPB. Pre-, intra- and post-surgery renal ultrasound was performed. During pulsatile CPB, the amplitude and the baseline flow were modified. Recordings of pulsed Doppler in intrarenal arteries were obtained by measuring maximum systolic velocity, minimum diastolic velocity, resistance index (RI) and acceleration time (AT).Statistical differences were found in ultrasounds pre-CPB between A50F50 modality (P=.013), A50F30 (P=.013) and A60F50 (P=.003). No statistically significance was found with A30F30 modality (P=.125).The decrease in the amplitude and the baseline flow of pulsatility during CPB shows a renal ultrasound morphology that is more similar to the physiological one. Subsequent studies using these characteristics during pulsatile CPB could thus show perfusion over the ARF that occurs after cardiac surgery.

The retromer acts as the gatekeeper blocking signaling mediated by beta-arrestin 1 from internalized cannabinoid 2 receptors. This work provides further confirmation of the relevance and prevalence of signaling from internalized receptors at endosomal compartments after ligand-induced endocytosis., G protein–coupled receptors mediate their complex functions through activation of signaling cascades from receptors localized at the cell surface and endosomal compartments. These signaling pathways are modulated by heterotrimeric G proteins and the scaffold proteins beta-arrestin 1 and 2. However, in contrast to the events occurring at the cell surface, our knowledge of the mechanisms controlling signaling from receptors localized at intracellular compartments is still very limited. Here we sought to investigate the intracellular signaling from cannabinoid 2 receptor (CB2R). First, we show that receptor internalization is required for agonist-induced phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). Then we demonstrate that ERK1/2 activation is mediated by beta-arrestin 1 from receptors localized exclusively at Rab4/5 compartments. Finally, we identify the retromer complex as a gatekeeper, terminating beta-arrestin 1–mediated ERK phosphorylation. These findings extend our understanding of the events controlling signaling from endocytosed receptors and identify the retromer as a modulator of beta-arrestin–mediated signaling from CB2R.

Laparoscopic radical cystectomy with lymphadenectomy and urinary diversion is an increasingly widespread operation. Studies are needed to support the oncological effectiveness and safety of this minimally invasive approach.A nonrandomised, comparative prospective study between open radical cystectomy (ORC) and laparoscopic radical cystectomy (LRC) was conducted in a university hospital. The main objective was to compare cancer-specific survival. The secondary objective was to compare the surgical results and complications according to the Clavien-Dindo scale.We treated 156 patients with high-grade invasive bladder cancer with either ORC (n=70) or LRC (n=86). The mean follow-up was 33.5±23.8 (range 12-96) months. The mean age was 66.9+9.4 years, and the male to female ratio was 19:1. Both groups were equivalent in age, stage, positive lymph nodes, in situ carcinoma, preoperative obstructive uropathy, adjuvant chemotherapy and type of urinary diversion. There were no differences between the groups in terms of cancer-specific survival (log-rank; P=.71). The histopathology stage was the only independent variable that predicted the prognosis. The hospital stay (P=.01) and operative transfusion rates (P=.002) were less for LRC. The duration of the surgery was greater for LRC (P.001). There were no differences in the total complications rate (p=.62) or major complications (P=.69). The risk of evisceration (P=.02), surgical wound infection (P=.005) and pneumonia (P=.017) was greater for ORC. The risk of rectal lesion (P=.017) and urethrorectal fistulae (P=.065) was greater for LRC.LRC is an equivalent treatment to ORC in terms of oncological efficacy and is advantageous in terms of transfusion rates and hospital stays but not in terms of operating room time and overall safety. Studies are needed to better define the specific safety profile for each approach.