Gravedad en pacientes traumáticos ingresados en UCI. Modelos fisiológicos y anatómicos / Severity scores in trauma patients admitted to ICU. Physiological and anatomic models

Introducción: Comparar los scores de gravedad anatómicos y fisiológicos en los pacientes traumáticos ingresados en unidad de cuidados intensivos (UCI) y crear modelos combinados que mejoren su precisión. Método: Estudio prospectivo de cohorte observacional. UCI polivalente de un hospital universitario de 2.o nivel. Se incluyeron los pacientes traumáticos mayores de 16 años ingresados en UCI (n=780). Se comparan los modelos anatómicos (ISS, NISS) con los modelos fisiológicos (T-RTS, APACHE II [APII]), MPM II). La probabilidad de muerte se calculó según metodología TRISS. La discriminación se valoró mediante curvas ROC (ABC [IC 95%]) y la calibración con el estadístico H de Hosmer-Lemeshow. Los modelos combinados se realizaron con metodología de árboles de clasificación tipo Chi Square Automatic Interaction Detection. Resultados: Mortalidad global del 14%. Los modelos fisiológicos son los que presentan mejores valores de discriminación (APII con 0,87 [0,84-0,90]). Todos los modelos tienen una mala calibración (p<0,01). El mejor modelo combinado es el que utiliza APII junto a ISS (0,88 [0,83-0,90]) y encuentra un grupo de pacientes (valores de APII entre 10-17) que necesita la puntuación ISS (punto de corte de 22) para diferenciar entre mortalidad del 7,5% asociada a pacientes mayores con antecedentes patológicos y del 25,0% en pacientes con mayor presencia de TCE. Conclusiones: Los modelos fisiológicos presentan ventajas sobre los anatómicos en los pacientes traumáticos ingresados en UCI. Los pacientes con puntuaciones bajas en los modelos fisiológicos requieren del análisis anatómico de las lesiones para determinar su gravedad

Introduction: The goals of this project were to compare both the anatomic and physiologic severity scores in trauma patients admitted to intensive care unit (ICU), and to elaborate mixed statistical models to improve the precision of the scores. Methods: A prospective study of cohorts. The combined medical/surgical ICU in a secondary university hospital. Seven hundred and eighty trauma patients admitted to ICU older than 16 years of age. Anatomic models (ISS and NISS) were compared and combined with physiological models (T-RTS, APACHE II [APII], and MPM II). The probability of death was calculated following the TRISS method. The discrimination was assessed using ROC curves (ABC [CI 95%]), and the calibration using the Hosmer-Lemeshoẃs H test. The mixed models were elaborated with the tree classification method type Chi Square Automatic Interaction Detection. Results: A 14% global mortality was recorded. The physiological models presented the best discrimination values (APII of 0.87 [0.84-0.90]). All models were affected by bad calibration (P<.01). The best mixed model resulted from the combination of APII and ISS (0.88 [0.83-0.90]). This model was able to differentiate between a 7.5% mortality for elderly patients with pathological antecedents and a 25% mortality in patients presenting traumatic brain injury, from a pool of patients with APII values ranging from 10 to 17 and an ISS threshold of 22. Conclusions: The physiological models perform better than the anatomical models in traumatic patients admitted to the ICU. Patients with low scores in the physiological models require an anatomic analysis of the injuries to determine their severity

Severity scores in trauma patients admitted to ICU. Physiological and anatomic models. / Gravedad en pacientes traumáticos ingresados en UCI. Modelos fisiológicos y anatómicos.

INTRODUCTION: The goals of this project were to compare both the anatomic and physiologic severity scores in trauma patients admitted to intensive care unit (ICU), and to elaborate mixed statistical models to improve the precision of the scores. METHODS: A prospective study of cohorts. The combined medical/surgical ICU in a secondary university hospital. Seven hundred and eighty trauma patients admitted to ICU older than 16 years of age. Anatomic models (ISS and NISS) were compared and combined with physiological models (T-RTS, APACHE II [APII], and MPM II). The probability of death was calculated following the TRISS method. The discrimination was assessed using ROC curves (ABC [CI 95%]), and the calibration using the Hosmer-Lemeshows H test. The mixed models were elaborated with the tree classification method type Chi Square Automatic Interaction Detection. RESULTS: A 14% global mortality was recorded. The physiological models presented the best discrimination values (APII of 0.87 [0.84-0.90]). All models were affected by bad calibration (P<.01). The best mixed model resulted from the combination of APII and ISS (0.88 [0.83-0.90]). This model was able to differentiate between a 7.5% mortality for elderly patients with pathological antecedents and a 25% mortality in patients presenting traumatic brain injury, from a pool of patients with APII values ranging from 10 to 17 and an ISS threshold of 22. CONCLUSIONS: The physiological models perform better than the anatomical models in traumatic patients admitted to the ICU. Patients with low scores in the physiological models require an anatomic analysis of the injuries to determine their severity.

Characterization of the Epigenetic Changes During Human Gonadal Primordial Germ Cells Reprogramming.

Epigenetic reprogramming is a central process during mammalian germline development. Genome-wide DNA demethylation in primordial germ cells (PGCs) is a prerequisite for the erasure of epigenetic memory, preventing the transmission of epimutations to the next generation. Apart from DNA demethylation, germline reprogramming has been shown to entail reprogramming of histone marks and chromatin remodelling. Contrary to other animal models, there is limited information about the epigenetic dynamics during early germ cell development in humans. Here, we provide further characterization of the epigenetic configuration of the early human gonadal PGCs. We show that early gonadal human PGCs are DNA hypomethylated and their chromatin is characterized by low H3K9me2 and high H3K27me3 marks. Similarly to previous observations in mice, human gonadal PGCs undergo dynamic chromatin changes concomitant with the erasure of genomic imprints. Interestingly, and contrary to mouse early germ cells, expression of BLIMP1/PRDM1 persists in through all gestational stages in human gonadal PGCs and is associated with nuclear lysine-specific demethylase-1. Our work provides important additional information regarding the chromatin changes associated with human PGCs development between 6 and 13 weeks of gestation in male and female gonads. Stem Cells 2016;34:2418-2428.

Complicaciones graves en la intubación orotraqueal en cuidados intensivos: estudio observacional y análisis de factores de riesgo / Severe complications of orotracheal intubation in the Intensive Care Unit: An observational study and analysis of risk factors

Objetivo Conocer las características de los procedimientos de intubación orotraqueal (IOT) en una Unidad de Medicina Intensiva, describir las complicaciones graves relacionadas con el procedimiento y los factores de riesgo asociados a su aparición. Diseño Estudio prospectivo de cohorte, observacional, durante un periodo de 2 años. Ámbito Unidad de Cuidados Intensivos polivalente de un hospital universitario de segundo nivel. Pacientes Se incluyeron todas las IOT (309 procedimientos) realizadas por el intensivista. Intervenciones Ninguna. Variables de interés principal Datos clínicos previos a la IOT, durante y posintubación, motivo de IOT y sus complicaciones. Análisis de factores de riesgo mediante regresión logística múltiple. Resultados El 76% de las IOT se realizaron de forma inmediata. Se llevaron a cabo mayoritariamente por el médico interno residente de la Unidad de Cuidados Intensivos (60%). El 34% de los procedimientos presentaron complicaciones graves con alteración respiratoria (16%), hemodinámica (5%) o ambas (10%). Fallecieron 3 pacientes (1%) y presentaron parada cardiaca el 2% de los casos. El análisis de regresión logística mostró que la edad (OR 1,1; IC 95%: 1,1-1,2), la tensión arterial sistólica≤90mmHg (OR 3,0; IC 95%: 1,4-6,4) y la SapO2≤90% (OR 4,4; IC 95%: 2,3-8,1) previos a la intubación, la presencia de secreciones (OR 2,2; IC 95%: 1,1-4,6) y la necesidad de más de un intento (OR 3,5; IC 95%: 1,4-8,7) fueron factores independientes para la aparición de complicaciones. Conclusiones La IOT del paciente crítico se asocia a complicaciones respiratorias y hemodinámicas. Los factores de riesgo independientes relacionados con la aparición de complicaciones fueron la edad avanzada, la hipotensión, la hipoxemia previa, las secreciones y la necesidad de más de un intento (AU)

Objective A study is made to determine the characteristics of endotracheal intubation (ETI) procedures performed in an Intensive Care Unit, and to describe the associated severe complications and related risk factors. Design A prospective cohort study involving a 2-year period was carried out. Setting The combined clinical/surgical Intensive Care Unit in a secondary university hospital. Patients All ETIs carried out by intensivists were included. Interventions None. Main variables We analyzed the data associated with the patient, the procedure and the postoperative complications after intubation. The study of risk factors was performed using multiple logistic regression analysis. Results Seventy-six percent of the ETIs were performed immediately. Most of them were carried out by Intensive Care Units residents (60%). A total of 34% of the procedures had severe complications, including respiratory (16%) or hemodynamic (5%) disorders, or both (10%). Three patients died (1%), and 2% of the subjects experienced cardiac arrest. Logistic regression analysis identified the following independent risk factors for complications: age (OR 1.1; 95% CI: 1.1-1.2), systolic blood pressure≤90mmHg (OR 3.0; 95% CI: 1.4-6.4) and SpO2≤90% (OR 4.4; 95% CI: 2.3-8.1) prior to intubation, the presence of secretions (OR 2.2; 95% CI: 1.1-4.6), and the need for more than one ETI attempt (OR 3.5; 95% CI: 1.4-8.7).Conclusions ETI in Intensive Care Unit patients is associated with respiratory and hemodynamic complications. The independent risk factors associated with the development of complications were advanced age, hypotension and previous hypoxemia, the presence of secretions, and the need for more than one ETI attempt (AU)

[Severe complications of orotracheal intubation in the Intensive Care Unit: An observational study and analysis of risk factors]. / Complicaciones graves en la intubación orotraqueal en cuidados intensivos: estudio observacional y análisis de factores de riesgo.

OBJECTIVE: A study is made to determine the characteristics of endotracheal intubation (ETI) procedures performed in an Intensive Care Unit, and to describe the associated severe complications and related risk factors. DESIGN: A prospective cohort study involving a 2-year period was carried out. SETTING: The combined clinical/surgical Intensive Care Unit in a secondary university hospital. PATIENTS: All ETIs carried out by intensivists were included. INTERVENTIONS: None. MAIN VARIABLES: We analyzed the data associated with the patient, the procedure and the postoperative complications after intubation. The study of risk factors was performed using multiple logistic regression analysis. RESULTS: Seventy-six percent of the ETIs were performed immediately. Most of them were carried out by Intensive Care Units residents (60%). A total of 34% of the procedures had severe complications, including respiratory (16%) or hemodynamic (5%) disorders, or both (10%). Three patients died (1%), and 2% of the subjects experienced cardiac arrest. Logistic regression analysis identified the following independent risk factors for complications: age (OR 1.1; 95% CI: 1.1-1.2), systolic blood pressure≤90mmHg (OR 3.0; 95% CI: 1.4-6.4) and SpO2≤90% (OR 4.4; 95% CI: 2.3-8.1) prior to intubation, the presence of secretions (OR 2.2; 95% CI: 1.1-4.6), and the need for more than one ETI attempt (OR 3.5; 95% CI: 1.4-8.7). CONCLUSIONS: ETI in Intensive Care Unit patients is associated with respiratory and hemodynamic complications. The independent risk factors associated with the development of complications were advanced age, hypotension and previous hypoxemia, the presence of secretions, and the need for more than one ETI attempt.

[Skin necrosis: report of eleven cases]. / Necrosis cutánea: un desafío para el médico.

Skin necrosis must be considered as a syndrome, because it is a clinical manifestation of different diseases. An early diagnosis is very important to choose the appropriate treatment. Therefore, its causes should be suspected and confirmed quickly. We report eleven patients with skin necrosis seen at our Department, caused by different etiologies: Warfarin-induced skin necrosis, loxoscelism, diabetic microangiopathy, ecthyma gangrenosum, disseminated intravascular coagulation, necrotizing vasculitis, paraneoplastic extensive necrotizing vasculitis, livedoid vasculopathy, necrotizing fasciitis, necrosis secondary to the use of vasoactive drugs and necrosis secondary to the use of cocaine. We also report the results of our literature review on the subject.

Clasificación de los trastornos mentales en la Unidad de Cuidados Intensivos / No disponible

Objetivo: Conocer la incidencia y características del trastorno mental (TM) en la UCI y definir una clasificación adaptada al entorno de UCI. Diseño: Estudio descriptivo y retrospectivo. Ámbito: Unidad de Cuidados Intensivos polivalente del Hospital Universitario Arnau de Vilanova de Lérida. Pacientes: Se incluyó 146 pacientes que ingresaron con TM durante un periodo de 5 anos (1 de enero de 2004 a 31 de diciembre de 2008).Variables de interés: Variables generales: clínico-demográficas, diagnóstico, procedimientos, gravedad, estancia y mortalidad. Variables específicas: antecedentes psiquiátricos, screening de tóxicos, valoración psiquiátrica, seguimiento y traslado a centro psiquiátrico. Clasificacióndel TM: 1) intoxicación aguda por sustancias (IS), 2) intento autolítico (IA) y 3) trastorno mental asociado al diagnóstico principal (TA).Resultados: Un total de 146 pacientes con TM (7,8%). Predominio de varones (74%) y más jóvenes(43,9 vs 55,3 anos, p < 0,001). La estancia en la UCI fue más corta (4 días vs 7 días, p < 0,001) y ˜hubo menor mortalidad hospitalaria (17,1 vs 25%, p < 0,05). Sin diferencias en nivel de gravedad pero más incidencia de neumonía (19,9 vs 13,8%, p < 0,05). El grupo IS (24,7%), más jóvenes, el grupo IA (36,3%) con predominio de mujeres y TA (39%) con estancia y mortalidad más altas. La consulta a Psiquiatría se realizó prioritariamente en IA (62,3%).Conclusiones: El TM es un problema relativamente frecuente en UCI. La colaboración con Psiquiatría es minoritaria y debe ser potenciada para conseguir un manejo integral del paciente crítico con TM (AU)

Purpose: To determine the incidence and characteristics of mental disorders (MD) in the Intensive Care Unit (ICU), and to define a classification system adapted to the ICU environment. Design: A retrospective, descriptive analysis. Setting: Intensive Care Unit, Arnau de Vilanova Hospital in Lérida (Spain).Patients: All patients with MD admitted during 5-year period (January, 1 2004 to December 31,2008).Main variables: General variables included clinical-demographic data, diagnostic variables, procedures, severity score, length of stay and mortality. Specific variables included psychiatric history, screening for substance abuse, psychiatric assessment, monitoring and transfer to a psychiatric center. Classification of the MD was as follows: 1) acute substance intoxication(SI); 2) suicide attempts (SA); and 3) MD associated with the main diagnosis (AMD).Results: A total of 146 patients had MD (7.8%); they were predominantly male (74%) and were younger than the general ICU population (43.9 vs. 55.3 years, p < 0.001). The ICU stays of the patients with MDs were shorter (4 days vs. 7 days, p < 0.001), and there was less hospital mortality (17.1 vs. 25%, p < 0.05). They also showed a higher incidence of pneumonia (19.9 vs. 13.8%,p < 0.05), but no differences in the level of severity were observed. The SI group (24.7%) contained the highest number of young people; the SA group (36.3%) showed a predominance of women; and the AMD (39%) group had the longest stays and the highest mortality. Psychiatric consultation was carried out mainly in the SA group (62.3%).Conclusions: MD is a relatively common problem in the ICU. Collaboration with the Psychiatry Department seldom occurs, but must be encouraged to develop fully integrated management of critical patients with MD (AU)

[Classification of mental disorders in the Intensive Care Unit]. / Clasificación de los trastornos mentales en la Unidad de Cuidados Intensivos.

PURPOSE: To determine the incidence and characteristics of mental disorders (MD) in the Intensive Care Unit (ICU), and to define a classification system adapted to the ICU environment. DESIGN: A retrospective, descriptive analysis. SETTING: Intensive Care Unit, Arnau de Vilanova Hospital in Lérida (Spain). PATIENTS: All patients with MD admitted during 5-year period (January, 1 2004 to December 31, 2008). MAIN VARIABLES: General variables included clinical-demographic data, diagnostic variables, procedures, severity score, length of stay and mortality. Specific variables included psychiatric history, screening for substance abuse, psychiatric assessment, monitoring and transfer to a psychiatric center. Classification of the MD was as follows: 1) acute substance intoxication (SI); 2) suicide attempts (SA); and 3) MD associated with the main diagnosis (AMD). RESULTS: A total of 146 patients had MD (7.8%); they were predominantly male (74%) and were younger than the general ICU population (43.9 vs. 55.3 years, p<0.001). The ICU stays of the patients with MDs were shorter (4 days vs. 7 days, p<0.001), and there was less hospital mortality (17.1 vs. 25%, p<0.05). They also showed a higher incidence of pneumonia (19.9 vs. 13.8%, p<0.05), but no differences in the level of severity were observed. The SI group (24.7%) contained the highest number of young people; the SA group (36.3%) showed a predominance of women; and the AMD (39%) group had the longest stays and the highest mortality. Psychiatric consultation was carried out mainly in the SA group (62.3%). CONCLUSIONS: MD is a relatively common problem in the ICU. Collaboration with the Psychiatry Department seldom occurs, but must be encouraged to develop fully integrated management of critical patients with MD.

Complete meiosis from human induced pluripotent stem cells.

Gamete failure-derived infertility affects millions of people worldwide; for many patients, gamete donation by unrelated donors is the only available treatment. Embryonic stem cells (ESCs) can differentiate in vitro into germ-like cells, but they are genetically unrelated to the patient. Using an in vitro protocol that aims at recapitulating development, we have achieved, for the first time, complete differentiation of human induced pluripotent stem cells (hiPSCs) to postmeiotic cells. Unlike previous reports using human ESCs, postmeiotic cells arose without the over-expression of germline related transcription factors. Moreover, we consistently obtained haploid cells from hiPSCs of different origin (keratinocytes and cord blood), produced with a different number of transcription factors, and of both genetic sexes, suggesting the independence of our approach from the epigenetic memory of the reprogrammed somatic cells. Our work brings us closer to the production of personalized human gametes in vitro.

IGF-I binding and receptor signal transduction in primary cell culture of muscle cells of gilthead sea bream: changes throughout in vitro development.

We examined the possibility of culturing muscle cells of gilthead sea bream in vitro and assessed variations in insulin-like growth factor-I (IGF-I) binding during myocyte development. The viability of the cell culture was determined by fluorescence-activated cell-sorting analysis, which showed that the percentage of dead cells decreased with cell differentiation. The intracellular reduction of MTT into formazan pigment was preferentially carried out as cells differentiated (from day 4) indicating an increase in metabolic activity. IGF-I-binding assays demonstrated that the number of receptors increased from 190 +/- 0.09 fmol/mg protein in myocytes at day 5 to 360 +/- 0.09 fmol/mg protein in myotubes at day 12. The affinity of IGF-I receptors did not change significantly during cell development (from 0.89 +/- 0.09 to 0.98 +/- 0.09 nM). The activation of various kinase (ERK 1/2 MAPK and Akt/PKB) proteins by IGFs and insulin was studied by means of Western blot analysis. Levels of MAPK-P increased after IGF and insulin treatment during the first stages of cell culture, with a low response being observed at day 15, whereas IGFs displayed a stimulatory effect on Akt-P throughout the cell culture period, even on day 15. This study thus shows that (1) gilthead sea bream myocytes can be cultured, (2) they express functional IGF-I receptors that increase in number as they differentiate in vitro; (3) IGF signalling transduction through IGF-I receptors stimulates the MAPK and Akt pathways, depending on the development stage of the muscle cell culture.

Role of insulin, insulin-like growth factors, and muscle regulatory factors in the compensatory growth of the trout (Oncorhynchus mykiss).

To examine the various mechanisms involved in compensatory growth in Oncorhynchus mykiss, an experimental protocol involving 1, 2 or 4 weeks of fasting followed by a single ad libitum re-feeding period of 4 weeks was designed for alevins. Morphological parameters including body weight, specific growth rates (SGR), and coefficient factor decreased significantly during fasting. Re-feeding accelerated growth and restored final body weight in groups previously fasted. Plasma insulin and glucose decreased in fasting, while normal levels were restored in all re-fed groups. The expression profile of insulin-like growth factors (IGFs) in liver and of the main muscle growth regulators in white muscle was examined using real-time quantitative RT-PCR. Fasting decreased the expression of IGF-I mRNA in both tissues, while re-feeding restored expression to control values. In contrast, IGF-II expression was not affected by any treatment in either tissue. Insulin- and IGF-I-binding assays in partial semi-purifications (of soluble proteins) in white skeletal muscle showed that insulin binding was not affected by either fasting or re-feeding, whereas fasting up-regulated IGF-I binding. The expression of IGFRIb mRNA in white skeletal muscle also increased with fasting, while IGFRIa increased with re-feeding, indicating that the two receptor isoforms are differentially regulated. The mRNA expression of myogenic regulator factors and fibroblast growth factors (FGFs) was not affected throughout the experiment, except for myogenin, which first decreased and then showed a rebound effect after 4 weeks of fasting. Myostatin mRNA expression did not change during fasting, although re-feeding caused a significant decrease. In conclusion, re-feeding of previously fasted trout induced compensatory growth. The differential regulation in muscle expression of IGF-I, IGF-I receptors, and myostatin indicates their contribution to this compensatory mechanism.