Rationale and study design for an Individualized PeriopeRative Open lung VEntilatory approach in Emergency Abdominal Laparotomy/scopy: study protocol for a prospective international randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPC) are the most frequent postoperative complications, with an estimated prevalence in elective surgery ranging from 20% in observational cohort studies to 40% in randomized clinical trials. However, the prevalence of PPCs in patients undergoing emergency abdominal surgery is not well defined. Lung-protective ventilation aims to minimize ventilator-induced lung injury and reduce PPCs. The open lung approach (OLA), which combines recruitment manoeuvres (RM) and positive end-expiratory pressure (PEEP) titration, aims to minimize areas of atelectasis and the development of PPCs; however, there is no conclusive evidence in the literature that OLA can prevent PPCs. The purpose of this study is to compare an individualized perioperative OLA with conventional standardized lung-protective ventilation in patients undergoing emergency abdominal surgery with clinical signs of intraoperative lung collapse. METHODS: Randomized international clinical trial to compare an individualized perioperative OLA (RM plus individualized PEEP and individualized postoperative respiratory support) with conventional lung-protective ventilation (standard PEEP of 5 cmH2O and conventional postoperative oxygen therapy) in patients undergoing emergency abdominal surgery with clinical signs of lung collapse. Patients will be randomised to open-label parallel groups. The primary outcome is any severe PPC during the first 7 postoperative days, including: acute respiratory failure, pneumothorax, weaning failure, acute respiratory distress syndrome, and pulmonary infection. The estimated sample size is 732 patients (366 per group). The final sample size will be readjusted during the interim analysis. DISCUSSION: The Individualized Perioperative Open-lung Ventilatory Strategy in emergency abdominal laparotomy (iPROVE-EAL) is the first multicentre, randomized, controlled trial to investigate whether an individualized perioperative approach prevents PPCs in patients undergoing emergency surgery.

Development of a cost-effective automated platform to produce human liver spheroids for basic and applied research.

Liver disease represents an increasing cause of global morbidity and mortality. Currently, liver transplant is the only treatment curative for end-stage liver disease. Donor organs cannot meet the demand and therefore scalable treatments and new disease models are required to improve clinical intervention. Pluripotent stem cells represent a renewable source of human tissue. Recent advances in three-dimensional cell culture have provided the field with more complex systems that better mimic liver physiology and function. Despite these improvements, current cell-based models are variable in performance and expensive to manufacture at scale. This is due, in part, to the use of poorly defined or cross-species materials within the process, severely affecting technology translation. To address this issue, we have developed an automated and economical platform to produce liver tissue at scale for modelling disease and small molecule screening. Stem cell derived liver spheres were formed by combining hepatic progenitors with endothelial cells and stellate cells, in the ratios found within the liver. The resulting tissue permitted the study of human liver biology 'in the dish' and could be scaled for screening. In summary, we have developed an automated differentiation system that permits reliable self-assembly of human liver tissue for biomedical application. Going forward we believe that this technology will not only serve as anin vitroresource, and may have an important role to play in supporting failing liver function in humans.

Características, evolución clínica y factores asociados a la mortalidad en UCI de los pacientes críticos infectados por SARS-CoV-2 en España: estudio prospectivo, de cohorte y multicéntrico / Patient characteristics, clinical course and factors associated to ICU mortality in critically ill patients infected with SARS-CoV-2 in Spain: a prospective, cohort, multicentre study

ANTECEDENTES: No se ha reportado plenamente la evolución clínica de los pacientes críticos de COVID-19 durante su ingreso en la unidad de cuidados intensivos (UCI), incluyendo las complicaciones médicas e infecciosas y terapias de soporte, así como su asociación con la mortalidad en ICU. OBJETIVO: El objetivo de este estudio es describir las características clínicas y la evolución de los pacientes ingresados en UCI por COVID-19, y determinar los factores de riesgo de la mortalidad en UCI de dichos pacientes. MÉTODOS: Estudio prospectivo, multi-céntrico y de cohorte, que incluyó a los pacientes críticos de COVID-19 ingresados en 30 UCIs de España y Andorra. Se incluyó a los pacientes consecutivos de 12 de Marzo a 26 de Mayo de 2020 si habían fallecido o habían recibido el alta de la UCI durante el periodo de estudio. Se reportaron los datos demográficos, síntomas, signos vitales, marcadores de laboratorio, terapias de soporte, terapias farmacológicas, y complicaciones médicas e infecciosas, realizándose una comparación entre los pacientes fallecidos y los pacientes dados de alta. RESULTADOS: Se incluyó a un total de 663 pacientes. La mortalidad general en UCI fue del 31% (203 pacientes). Al ingreso en UCI los no supervivientes eran más hipoxémicos [SpO2 sin mascarilla de no reinhalación, de 90 (RIC 83-93) vs 91 (RIC 87-94); p < 0,001] y con mayor puntuación en la escala SOFA - Evaluación de daño orgánico secuencial - [SOFA, 7 (RIC 5-9) vs 4 (RIC 3-7); p < 0,001]. Las complicaciones fueron más frecuentes en los no supervivientes: síndrome de distrés respiratorio agudo (SDRA) (95% vs 89%; p = 0,009), insuficiencia renal aguda (IRA) (58% vs 24%; p < 10−16), shock (42% vs 14%; p < 10−13), y arritmias (24% vs 11%; p < 10−4). Las súper-infecciones respiratorias, infecciones del torrente sanguíneo y los shock sépticos fueron más frecuentes en los no supervivientes (33% vs 25%; p = 0,03, 33% vs 23%; p = 0,01 y 15% vs 3%, p = 10−7), respectivamente. El modelo de regresión multivariable reflejó que la edad estaba asociada a la mortalidad, y que cada año incrementaba el riesgo de muerte en un 1% (95%IC: 1-10, p = 0,014). Cada incremento de 5 puntos en la escala APACHE II predijo de manera independiente la mortalidad [OR: 1,508 (1,081, 2,104), p = 0,015]. Los pacientes con IRA [OR: 2,468 (1,628, 3,741), p < 10−4)], paro cardiaco [OR: 11,099 (3,389, 36,353), p = 0,0001], y shock séptico [OR: 3,224 (1,486, 6,994), p = 0,002] tuvieron un riesgo de muerte incrementado. CONCLUSIONES: Los pacientes mayores de COVID-19 con puntuaciones APACHE II más altas al ingreso, que desarrollaron IRA en grados II o III y/o shock séptico durante la estancia en UCI tuvieron un riesgo de muerte incrementado. La mortalidad en UCI fue del 31%

BACKGROUND: The clinical course of COVID-19 critically ill patients, during their admission in the intensive care unit (UCI), including medical and infectious complications and support therapies, as well as their association with in-ICU mortality has not been fully reported. OBJECTIVE: This study aimed to describe clinical characteristics and clinical course of ICU COVID-19 patients, and to determine risk factors for ICU mortality of COVID-19 patients. METHODS: Prospective, multicentre, cohort study that enrolled critically ill COVID-19 patients admitted into 30 ICUs from Spain and Andorra. Consecutive patients from March 12th to May 26th, 2020 were enrolled if they had died or were discharged from ICU during the study period. Demographics, symptoms, vital signs, laboratory markers, supportive therapies, pharmacological treatments, medical and infectious complications were reported and compared between deceased and discharged patients. RESULTS: A total of 663 patients were included. Overall ICU mortality was 31% (203 patients). At ICU admission non-survivors were more hypoxemic [SpO2 with non-rebreather mask, 90 (IQR 83-93) vs 91 (IQR 87-94); p < 0.001] and with higher sequential organ failure assessment score [SOFA, 7 (IQR 5-9) vs 4 (IQR 3-7); p < 0.001]. Complications were more frequent in non-survivors: acute respiratory distress syndrome (ARDS) (95% vs 89%; p = 0.009), acute kidney injury (AKI) (58% vs 24%; p < 10−16), shock (42% vs 14%; p < 10−13), and arrhythmias (24% vs 11%; p < 10−4). Respiratory super-infection, bloodstream infection and septic shock were higher in non-survivors (33% vs 25%; p = 0.03, 33% vs 23%; p = 0.01 and 15% vs 3%, p = 10−7), respectively. The multivariable regression model showed that age was associated with mortality, with every year increasing risk-of-death by 1% (95%CI: 1-10, p = 0.014). Each 5-point increase in APACHE II independently predicted mortality [OR: 1.508 (1.081, 2.104), p = 0.015]. Patients with AKI [OR: 2.468 (1.628, 3.741), p < 10−4)], cardiac arrest [OR: 11.099 (3.389, 36.353), p = 0.0001], and septic shock [OR: 3.224 (1.486, 6.994), p = 0.002] had an increased risk-of-death. CONCLUSIONS: Older COVID-19 patients with higher APACHE II scores on admission, those who developed AKI grades II or III and/or septic shock during ICU stay had an increased risk-of-death. ICU mortality was 31%

Patient characteristics, clinical course and factors associated to ICU mortality in critically ill patients infected with SARS-CoV-2 in Spain: A prospective, cohort, multicentre study. / Características, evolución clínica y factores asociados a la mortalidad en UCI de los pacientes críticos infectados por SARS-CoV-2 en España: estudio prospectivo, de cohorte y multicéntrico.

BACKGROUND: The clinical course of COVID-19 critically ill patients, during their admission in the intensive care unit (UCI), including medical and infectious complications and support therapies, as well as their association with in-ICU mortality has not been fully reported. OBJECTIVE: This study aimed to describe clinical characteristics and clinical course of ICU COVID-19 patients, and to determine risk factors for ICU mortality of COVID-19 patients. METHODS: Prospective, multicentre, cohort study that enrolled critically ill COVID-19 patients admitted into 30 ICUs from Spain and Andorra. Consecutive patients from March 12th to May 26th, 2020 were enrolled if they had died or were discharged from ICU during the study period. Demographics, symptoms, vital signs, laboratory markers, supportive therapies, pharmacological treatments, medical and infectious complications were reported and compared between deceased and discharged patients. RESULTS: A total of 663 patients were included. Overall ICU mortality was 31% (203 patients). At ICU admission non-survivors were more hypoxemic [SpO2 with non-rebreather mask, 90 (IQR 83 to 93) vs. 91 (IQR 87 to 94); P<.001] and with higher sequential organ failure assessment score [SOFA, 7 (IQR 5 to 9) vs. 4 (IQR 3 to 7); P<.001]. Complications were more frequent in non-survivors: acute respiratory distress syndrome (ARDS) (95% vs. 89%; P=.009), acute kidney injury (AKI) (58% vs. 24%; P<10-16), shock (42% vs. 14%; P<10-13), and arrhythmias (24% vs. 11%; P<10-4). Respiratory super-infection, bloodstream infection and septic shock were higher in non-survivors (33% vs. 25%; P=.03, 33% vs. 23%; P=.01 and 15% vs. 3%, P=10-7), respectively. The multivariable regression model showed that age was associated with mortality, with every year increasing risk-of-death by 1% (95%CI: 1 to 10, P=.014). Each 5-point increase in APACHE II independently predicted mortality [OR: 1.508 (1.081, 2.104), P=.015]. Patients with AKI [OR: 2.468 (1.628, 3.741), P<10-4)], cardiac arrest [OR: 11.099 (3.389, 36.353), P=.0001], and septic shock [OR: 3.224 (1.486, 6.994), P=.002] had an increased risk-of-death. CONCLUSIONS: Older COVID-19 patients with higher APACHE II scores on admission, those who developed AKI grades ii or iii and/or septic shock during ICU stay had an increased risk-of-death. ICU mortality was 31%.

Guía de práctica clínica para la elección del fluido de restauración volémica perioperatoria en los pacientes adultos intervenidos de cirugía no cardiaca / Clinical practice guide for the choice of perioperative volume-restoring fluid in adult patients undergoing non-cardiac surgery

Esta Guía de Práctica Clínica responde a preguntas clínicas sobre seguridad en la elección de fluido (cristaloide, coloide o Hidroxietilalmidón 130) en pacientes que precisan restauración volémica en el periodo perioperatorio de cirugía no cardiaca. A partir del resumen de la evidencia, se elaboraron las recomendaciones siguiendo la metodología GRADE. En esta población se sugiere la fluidoterapia basada en la administración de cristaloides, (recomendación débil, calidad de la evidencia baja). En las situaciones en las que la restauración volémica no se alcance sólo con cristaloides, se sugiere utilizar coloides sintéticos (Hidroxietilalmidón 130 o gelatina fluida modificada) en lugar de Albúmina 5% (recomendación débil, calidad de la evidencia baja). La elección y dosificación de coloide deberán basarse en las características del producto, comorbilidad del paciente y experiencia del anestesiólogo (AU)

The present Clinical practice guide responds to the clinical questions about security in the choice of fluid (crystalloid, colloid or hydroxyethyl starch 130) in patients who require volume replacement during perioperative period of non-cardiac surgeries. From the evidence summary, recommendations were made following the GRADE methodology. In this population fluid therapy based on crystalloids is suggested (weak recommendation, low quality evidence). In the events where volume replacement is not reached with crystalloids, the use of synthetic colloids (hydroxyethyl starch 130 or modified fluid gelatin) is suggested instead of 5% albumin (weak recommendation, low quality evidence). The choice and dosage of the colloid should be based in the product characteristics, patient comorbidity and anesthesiologist's experience (AU)

Clinical practice guide for the choice of perioperative volume-restoring fluid in adult patients undergoing non-cardiac surgery.

The present Clinical practice guide responds to the clinical questions about security in the choice of fluid (crystalloid, colloid or hydroxyethyl starch 130) in patients who require volume replacement during perioperative period of non-cardiac surgeries. From the evidence summary, recommendations were made following the GRADE methodology. In this population fluid therapy based on crystalloids is suggested (weak recommendation, low quality evidence). In the events where volume replacement is not reached with crystalloids, the use of synthetic colloids (hydroxyethyl starch 130 or modified fluid gelatin) is suggested instead of 5% albumin (weak recommendation, low quality evidence). The choice and dosage of the colloid should be based in the product characteristics, patient comorbidity and anesthesiologist's experience.

Breve visión histórica de la vitamina D / Short historic view of Vitamin D

No disponible

Beta-cell dysfunction in first-degree relatives of patients with non-insulin-dependent diabetes mellitus.

To analyse the relationship between age, glucose tolerance, beta-cell function, and insulin sensitivity in preclinical states of non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), we have done a cross-sectional, age-stratified analysis of 86 non-diabetic first-degree relatives of NIDDM patients and 49 controls with similar age, sex, and BMI. A 5 mg kg ideal body weight-1 min-1 for 60 min of continuous infusion of glucose with model assessment (CIGMA) of serum glucose and C-peptide values at the end of the infusion was used to determine glucose tolerance and beta-cell function. Insulin sensitivity was estimated by modelling basal serum glucose and insulin values. Relatives and controls were divided into tertiles on the basis of age. Relatives had higher basal (5.3 vs 5 mmol l-1, p = 0.02) and achieved serum glucose (9.1 vs 8.4 mmol l-1, p = 0.01), lower beta-cell function (128 vs 145%, p = 0.007), and lower insulin sensitivity (37 vs 43%, p = 0.002). Beta-cell function declined with age in relatives (from 139% in young subjects to 134% in intermediate subjects and to 111% in older subjects, p = 0.002) and this decline was associated with an increase in basal serum glucose (from 5.1 to 5.3 and to 5.7 mmol l-1, p = 0.000) and achieved glucose (from 8.3 to 9.1 and to 9.3 mmol l-1, p = 0.038), without significant changes in insulin sensitivity. These trends were observed even after the exclusion of subjects with mild glucose intolerance. We conclude that both beta-cell dysfunction and insulin resistance are present in first-degree relatives of NIDDM. The progression of beta-cell dysfunction and glucose intolerance with age suggests that beta-cell dysfunction is the key factor in the apparition and progression of the disease.

Conducta terapeutica ante algunas formas de insuficiencia venosa cronica asociada a varices superficiales de los miembros inferiores. / Therapeutic procedure of some forms of chronic venous insufficiency associated with superficial varicose veins of the lower limb

Se considera la experiencia en el tratamiento de 165 pacientes portadores de insuficiencia venosa profunda o comunicante asociada a varices superficiales. La conducta quirurgica aconsejada es la combinada, actuando sobre la totalidad de las venas enfermas. Desde el punto de vista etiopatogenico los autores se inclinan ante la posibilidad de la suma de causas esenciales en enfermos en los que se instala trombosis venosa de sectores profundos o comunicantes

Conducta terapeutica ante algunas formas de insuficiencia venosa cronica asociada a varices superficiales de los miembros inferiores. / Therapeutic procedure of some forms of chronic venous insufficiency associated with superficial varicose veins of the lower limb

Se considera la experiencia en el tratamiento de 165 pacientes portadores de insuficiencia venosa profunda o comunicante asociada a varices superficiales. La conducta quirurgica aconsejada es la combinada, actuando sobre la totalidad de las venas enfermas. Desde el punto de vista etiopatogenico los autores se inclinan ante la posibilidad de la suma de causas esenciales en enfermos en los que se instala trombosis venosa de sectores profundos o comunicantes