Study of the relationship between regional cerebral saturation and pCO2 changes during mechanical ventilation to evaluate modifications in cerebral perfusion in a newborn piglet model.

Near-infrared spectroscopy (NIRS) could be a useful continuous, non-invasive technique for monitoring the effect of partial pressure of carbon dioxide (PaCO2) fluctuations in the cerebral circulation during ventilation. The aim of this study was to examine the efficacy of NIRS to detect acute changes in cerebral blood flow following PaCO2 fluctuations after confirming the autoregulation physiology in piglets. Fourteen piglets (<72 h of life) were studied. Mean arterial blood pressure, oxygen saturation, pH, glycemia, hemoglobin, electrolytes, and temperature were monitored. Eight animals were used to evaluate brain autoregulation, assessing superior cava vein Doppler as a proxy of cerebral blood flow changing mean arterial blood pressure. Another 6 animals were used to assess hypercapnia generated by decreasing ventilatory settings and complementary CO2 through the ventilator circuit and hypocapnia due to increasing ventilatory settings. Cerebral blood flow was determined by jugular vein blood flow by Doppler and continuously monitored with NIRS. A decrease in PaCO2 was observed after hyperventilation (47.6±2.4 to 29.0±4.9 mmHg). An increase in PaCO2 was observed after hypoventilation (48.5±5.5 to 90.4±25.1 mmHg). A decrease in cerebral blood flow after hyperventilation (21.8±10.4 to 15.1±11.0 mL/min) and an increase after hypoventilation (23.4±8.4 to 38.3±10.5 mL/min) were detected by Doppler ultrasound. A significant correlation was found between cerebral oxygenation and Doppler-derived parameters of blood flow and PaCO2. Although cerebral NIRS monitoring is mainly used to detect changes in regional brain oxygenation, modifications in cerebral blood flow following experimental PaCO2 changes were detected in newborn piglets when no other important variables were modified.

Study of the relationship between regional cerebral saturation and pCO2 changes during mechanical ventilation to evaluate modifications in cerebral perfusion in a newborn piglet model

Near-infrared spectroscopy (NIRS) could be a useful continuous, non-invasive technique for monitoring the effect of partial pressure of carbon dioxide (PaCO2) fluctuations in the cerebral circulation during ventilation. The aim of this study was to examine the efficacy of NIRS to detect acute changes in cerebral blood flow following PaCO2 fluctuations after confirming the autoregulation physiology in piglets. Fourteen piglets (<72 h of life) were studied. Mean arterial blood pressure, oxygen saturation, pH, glycemia, hemoglobin, electrolytes, and temperature were monitored. Eight animals were used to evaluate brain autoregulation, assessing superior cava vein Doppler as a proxy of cerebral blood flow changing mean arterial blood pressure. Another 6 animals were used to assess hypercapnia generated by decreasing ventilatory settings and complementary CO2 through the ventilator circuit and hypocapnia due to increasing ventilatory settings. Cerebral blood flow was determined by jugular vein blood flow by Doppler and continuously monitored with NIRS. A decrease in PaCO2 was observed after hyperventilation (47.6±2.4 to 29.0±4.9 mmHg). An increase in PaCO2 was observed after hypoventilation (48.5±5.5 to 90.4±25.1 mmHg). A decrease in cerebral blood flow after hyperventilation (21.8±10.4 to 15.1±11.0 mL/min) and an increase after hypoventilation (23.4±8.4 to 38.3±10.5 mL/min) were detected by Doppler ultrasound. A significant correlation was found between cerebral oxygenation and Doppler-derived parameters of blood flow and PaCO2. Although cerebral NIRS monitoring is mainly used to detect changes in regional brain oxygenation, modifications in cerebral blood flow following experimental PaCO2 changes were detected in newborn piglets when no other important variables were modified.

SARS-CoV-2 IgG response in symptomatic and asymptomatic COVID-19-infected healthcare workers.

BACKGROUND: Healthcare workers (HCWs) accounted for a significant proportion of COVID-19 infections worldwide. Retrospective seroprevalence surveys are often used to screen for unidentified previous infection with SARS-CoV-2. However, the rate of humoral response in HCWs affected by COVID-19 is not well-defined. AIMS: To assess the specific IgG humoral response in symptomatic and asymptomatic SARS-CoV-2-infected HCWs and identify potential factors associated with humoral response. METHODS: We prospectively recruited 204 HCWs with RT-PCR-confirmed COVID-19 infection to evaluate SARS-CoV-2 humoral response. Serum-IgG antibodies against SARS-CoV-2 were analysed using two commercially available serological assays. A logistic regression was performed to identify independent factors associated with positive IgG serology test. RESULTS: Overall, the SARS-CoV-2 IgG seropositivity rate was 77%. This seropositivity rate was higher in symptomatic than in asymptomatic COVID-19 infection (83% versus 57%; P < 0.001) and in older HCWs.. The seropositivity rate did not diminish with time. In logistic regression, only a history of COVID-19 symptoms and age were identified as independent factors associated with the detection of anti-SARS-CoV-2 IgG antibodies. CONCLUSIONS: SARS-CoV-2 IgG antibodies are found significantly more frequently in symptomatic and in older HCWs. The fact that not all COVID-19 HCWs develop detectable IgG is vital for the interpretation of COVID-19 seroprevalence surveys.

Factors related to limitation of life support within 48h of intensive care unit admission: A multicenter study / Factores relacionados con la limitación del tratamiento de soporte vital en las primeras 48h de ingreso en unidades de cuidados intensivos: estudio multicéntrico

Objective: To determine factors related to limitations on life support within 48h of intensive care unit (ICU) admission. Study design: Prospective multicenter study. Setting: Eleven ICUs. Patients: All patients who died and/or had limitations on life support after ICU admission during a four-month period. Variables: Patient characteristics, hospital characteristics, characteristics of limitations on life support. Time-to-first-limitation was classified as early (<48h of admission) or late (≥48h). We performed univariate, multivariate analyses and CHAID (chi-square automatic interaction detection) analysis of variables associated with limitation of life support within 48h of ICU admission. Results: 3335 patients were admitted; 326 (9.8%) had limitations on life support. A total of 344 patients died; 247 (71.8%) had limitations on life support (range among centers, 58.6%-84.2%). The median (p25-p75) time from admission to initial limitation was 2 (0-7) days. CHAID analysis found that the modified Rankin score was the variable most closely related with early limitations. Among patients with Rankin >2, early limitations were implemented in 71.7% (OR=2.5; 95% CI: 1.5-4.4) and lung disease was the variable most strongly associated with early limitations (OR=12.29; 95% CI: 1.63-255.91). Among patients with Rankin ≤2, 48.8% had early limitations; patients admitted after emergency surgery had the highest rate of early limitations (66.7%; OR=2.4; 95% CI: 1.1-5.5). Conclusion: Limitations on life support are common, but the practice varies. Quality of life has the greatest impact on decisions to limit life support within 48h of admission

Objetivo: Determinar los factores relacionados con la limitación del tratamiento de soporte vital (LTSV) en las primeras 48h de ingreso en Unidades de Cuidados Intensivos (UCI). Diseño: Multicéntrico prospectivo. Ámbito: Once UCI. Pacientes: Pacientes fallecidos y/o en los que se aplicó LTSV durante 4 meses. Variables de interés: Características de pacientes, hospital y LTSV. Se definió LTSV precoz la que ocurría en las primeras 48h de ingreso y tardía >48h. Realizamos análisis univariado, multivariado y árbol de decisión chi-square automatic interaction detection (CHAID) con las variables asociadas con LTSV en las primeras 48h. Resultados: Incluidos 3.335 pacientes, en 326 (9,8%) se aplicó LTSV y 344 fallecieron; de estos 247 (71,8%) se limitaron (variabilidad interhospitalaria: 58,6-84,2%). La mediana de tiempo (p25-p75) entre el ingreso y la LTSV inicial fue de 2 (0-7) días. El análisis CHAID evidenció que la escala de Rankin modificada fue la variable más estrechamente relacionada con la limitación precoz. Entre los pacientes con Rankin>2 la LTSV precoz se realizó en el 71,7% (OR=2,5; IC 95%: 1,5-4,4) y la enfermedad pulmonar fue la variable más relacionada con la LTSV precoz (OR=12,29; IC 95%: 1,63-255,91). Entre los pacientes con Rankin≤2, la LTSV precoz ocurrió en el 48,8% siendo los pacientes con cirugía urgente aquellos con mayor LTSV precoz (66,7%; OR=2,4; IC 95%: 1,1-5,5). Conclusión: La LTSV es común pero la práctica es variable. La calidad de vida es la variable que mayor impacto tiene sobre la LTSV en las primeras 48h del ingreso en la UCI

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.

Factors related to limitation of life support within 48h of intensive care unit admission: A multicenter study.

OBJECTIVE: To determine factors related to limitations on life support within 48h of intensive care unit (ICU) admission. STUDY DESIGN: Prospective multicenter study. SETTING: Eleven ICUs. PATIENTS: All patients who died and/or had limitations on life support after ICU admission during a four-month period. VARIABLES: Patient characteristics, hospital characteristics, characteristics of limitations on life support. Time-to-first-limitation was classified as early (<48h of admission) or late (≥48h). We performed univariate, multivariate analyses and CHAID (chi-square automatic interaction detection) analysis of variables associated with limitation of life support within 48h of ICU admission. RESULTS: 3335 patients were admitted; 326 (9.8%) had limitations on life support. A total of 344 patients died; 247 (71.8%) had limitations on life support (range among centers, 58.6%-84.2%). The median (p25-p75) time from admission to initial limitation was 2 (0-7) days. CHAID analysis found that the modified Rankin score was the variable most closely related with early limitations. Among patients with Rankin >2, early limitations were implemented in 71.7% (OR=2.5; 95% CI: 1.5-4.4) and lung disease was the variable most strongly associated with early limitations (OR=12.29; 95% CI: 1.63-255.91). Among patients with Rankin ≤2, 48.8% had early limitations; patients admitted after emergency surgery had the highest rate of early limitations (66.7%; OR=2.4; 95% CI: 1.1-5.5). CONCLUSION: Limitations on life support are common, but the practice varies. Quality of life has the greatest impact on decisions to limit life support within 48h of admission.

[Bacteremia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. A retrospective study of 7 years]. / Bacteriemia por Klebsiella pneumoniae productora de carbapenemasa tipo KPC. Estudio comparativo y evolución en 7 años.

OBJECTIVE: Bacteremia caused by Klebsiella pneumoniae carbapenemase-producing strains (Kp-KPC) is associated with high mortality. The hypothesis of our work is that there was an increase in the levels of resistance to different antimicrobials in Kp-KPC isolated from bacteremia. METHODS: Retrospective and descriptive study in two periods: Period 1 (P1) 2010-2014 and period 2 (P2) 2015-2016. We included patients ≥18 years old with bacteremia caused by Kp-KPC in a General Hospital. We defined active drug (AD) if it was in vitro susceptible and in the case of meropenem if it had a MIC ≤ 8 mg/L in combination treatment. RESULTS: Fifty episodes of bacteremia caused by Kp-KPC were analyzed in 45 patients. (P1: 21 and P2: 29). The following variables were similar in both periods: median age (53 vs. 52 years); male sex (45 vs. 62%); site of infection: primary bacteremia (52 vs.45%), bacteremia associated with catheter (24 vs.17%), and other (24 vs. 38%). During P2 there was a significant increase in colistin resistance (28 vs. 69%) (p <0.01), an increase in MIC to meropenem ≥ 16 mg/L (74 and 97%) (p = 0.02), and decrease in tigecycline resistance (29 vs. 4%) (p = 0.02). The overall mortality was 40 in P1 and 32% in P2 (p=0.7). There was not difference in mortality when the definitive treatment was with an active antimicrobial vs. two active antimicrobials, as well as between the different antimicrobials used. CONCLUSIONS: There was a significant increase in bacteremia caused by Kp-KPC and the level of colistin resistance and MIC to meropenem. Overall mortality was high in both periods.

Litio para el tratamiento de la esclerosis lateral amiotrófica: mucho ruido para nada / Lithium for treatment of amyotrophic lateral sclerosis: much ado about nothing

Introducción: El litio fue propuesto en 2008 como un candidato eficaz en el tratamiento de ELA tras reportarse que era capaz de retrasar el deterioro funcional en un 40% y que ninguno de los 16 pacientes tratados con una combinación de litio más riluzole falleció durante un periodo de seguimiento de 15 meses. Los excelentes resultados de este estudio piloto despertaron una gran expectativa en pacientes, familiares, asociaciones de enfermos y comunidad científica. Consecuencia directa de esta noticia fue la puesta en marcha de numerosos ensayos clínicos en fase ii. Muchos de los pacientes, que no pudieron ser incluidos en estos estudios, utilizaron todos sus recursos para acceder a este fármaco mediante uso compasivo. Objetivos: Evaluar la eficacia del litio en ELA mediante un metaanálisis de la información reportada en 12 de estos estudios. Se analiza su calidad metodológica. Material y métodos: Se realizaron búsquedas en MEDLINE, EMBASE y Registros Cochrane del Grupo de Enfermedades Neuromusculares, ClinicalTrials.gov y EudraCT (enero de 1996-agosto de 2012). Resultados: Hasta la fecha disponemos de información de más de 1.100 pacientes tratados con litio. Lamentablemente los resultados obtenidos no confirman el efecto positivo descrito en el estudio piloto y sugieren que este fármaco es ineficaz para detener la progresión de la enfermedad. Dos ensayos tuvieron que ser suspendidos antes del plazo previsto por ineficacia del fármaco y por numerosos efectos adversos. En un estudio publicado recientemente se descarta también cualquier posibilidad de un mínimo efecto. Conclusiones: Hay evidencia de que el litio no ofrece beneficios a corto plazo en ELA. Al comparar el grupo de pacientes tratados con litio + riluzole con el grupo control tratado con riluzole no se observan diferencias estadísticamente significativas en las tasas de deterioro funcional o de deterioro de la función respiratoria ni tampoco en la supervivencia. No hay tampoco evidencia de que sea superior al placebo

Introduction: Lithium was proposed in 2008 as an effective candidate in the treatment of ALS after a report claimed that it was able to delay functional deterioration by 40% and that none of the 16 patients treated with a combination of lithium plus riluzole had died during a 15-month follow-up period. The excellent results of this pilot study engendered considerable optimism among patients, their families, patients’ associations, and the scientific community. This report sparked numerous phase ii clinical trials. Many patients who were not included in these studies used all resources at their disposal to access the drug as treatment under a compassionate use programme. Objectives: To evaluate the effectiveness of lithium in ALS using a meta-analysis of the information reported in 12 studies which were examined for methodological quality. Material and methods: Searches were performed using MEDLINE, EMBASE, the Cochrane Neuromuscular Disease Group Trials Register, ClinicalTrials.gov, and EudraCT (January 1996-August 2012). Results: To date, we have information on more 1100 patients treated with lithium. Unfortunately, the results do not confirm the positive effect described in the pilot study, which suggests that this drug is not effective at slowing disease progression. Two trials had to be suspended before the scheduled completion date due to the ineffectiveness of the drug as well as numerous adverse effects. A recently published study also ruled out any possible modest effect. Conclusions: There is evidence to suggest that lithium has no short-term benefits in ALS. A comparison of the group of patients treated with lithium + riluzole and the control group treated with riluzole alone showed no statistically significant differences in rates of functional decline, deterioration of respiratory function, or survival time. Furthermore, there was no evidence that it was more effective than the placebo

[Antimicrobial susceptibility of Gram-negative bacilli of community acquired intra-abdominal infections in a hospital at Buenos Aires, Argentina]. / Sensiblidad antimicrobiana de bacilos gramnegativos de infecciones intraabdominales de la comunidad en un hospital de la ciudad de Buenos Aires, Argentina.

OBJECTIVE: Community acquired complicated intra-abdominal infections (cIAI) are a common condition. Few data are available about the level of antimicrobial resistance of Gram-negative bacteria isolated from community acquired cIAIs in Argentina. METHODS: Retrospective-prospective observational study (March 2010 to February 2012). Gram-negative bacteria antimicrobial susceptibility of isolates from community acquired cIAIs were evaluated. RESULTS: During this period, a total of 85 patients were included and 138 pathogens were collected. Male sex: 58%. Median age: 33. Monomicrobial cultures were obtained in 49% of the cases. Ninety (65%) corresponded to Gram-negative organisms, and 48 (38%) to Gram-positive cocci. Gram-negative organisms most frequently observed were: Escherichia coli 76%, Klebsiella pneumoniae 8%, Pseudomonas aeruginosa 7% and Enterobacter spp. 6%. E. coli and K. pneumoniae showed a high percentage of strains resistance to ciprofloxacin of 37% and 29%, respectively. Similarly, resistance to ampicillin/sulbactam was observed in a 16% of the E. coli isolates. The prevalence of multiresistant Gram-negative organisms was 38%. CONCLUSIONS: A high level of resistance to antimicrobials was observed in community acquired cIAIs, mainly to ciprofloxacin and ampicillin/sulbactam two of the most used antimicrobial for empirically treatment of cIAIs in our country. In addition a significant proportion of multiresistant Gram-negative organisms were identified.

Lithium for treatment of amyotrophic lateral sclerosis: much ado about nothing. / Litio para el tratamiento de la esclerosis lateral amiotrófica: mucho ruido para nada.

INTRODUCTION: Lithium was proposed in 2008 as an effective candidate in the treatment of ALS after a report claimed that it was able to delay functional deterioration by 40% and that none of the 16 patients treated with a combination of lithium plus riluzole had died during a 15-month follow-up period. The excellent results of this pilot study engendered considerable optimism among patients, their families, patients' associations, and the scientific community. This report sparked numerous phase ii clinical trials. Many patients who were not included in these studies used all resources at their disposal to access the drug as treatment under a compassionate use programme. OBJECTIVES: To evaluate the effectiveness of lithium in ALS using a meta-analysis of the information reported in 12 studies which were examined for methodological quality. MATERIAL AND METHODS: . Searches were performed using MEDLINE, EMBASE, the Cochrane Neuromuscular Disease Group Trials Register, ClinicalTrials.gov, and EudraCT (January 1996-August 2012). RESULTS: To date, we have information on more 1100 patients treated with lithium. Unfortunately, the results do not confirm the positive effect described in the pilot study, which suggests that this drug is not effective at slowing disease progression. Two trials had to be suspended before the scheduled completion date due to the ineffectiveness of the drug as well as numerous adverse effects. A recently published study also ruled out any possible modest effect. CONCLUSIONS: There is evidence to suggest that lithium has no short-term benefits in ALS. A comparison of the group of patients treated with lithium+riluzole and the control group treated with riluzole alone showed no statistically significant differences in rates of functional decline, deterioration of respiratory function, or survival time. Furthermore, there was no evidence that it was more effective than the placebo.

Potencialidad de donación de órganos en muerte encefálica y limitación del tratamiento de soporte vital en los pacientes neurocríticos / Brain death organ donation potential and life support therapy limitation in neurocritical patients

OBJETIVO: Analizar el perfil, la incidencia de limitación de tratamiento de soporte vital (LTSV) y la potencialidad de donación de órganos en pacientes neurocríticos. DISEÑO: Multicéntrico prospectivo. ÁMBITO: Nueve centros autorizados para extracción de órganos para trasplante. PACIENTES: Todos los pacientes ingresados en el hospital con GCS < 8 durante 6 meses fueron seguidos hasta su alta o hasta 30 días de estancia hospitalaria. Variables de interés: Datos demográficos, causa del coma, situación clínica al ingreso y evolución. Incidencia de LTSV, muerte encefálica (ME) y donación de órganos. RESULTADOS: Se incluyó a 549 pacientes. Edad media 59,0 ± 14,5. El 27,0% de los comas fueron por hemorragias cerebrales. Se aplicó LTSV en 176 pacientes (32,1%). En 78 casos consistió en no ingreso en la UCI. La edad, presencia de contraindicaciones y determinadas causas del coma se asociaron a LTSV. Fallecieron 319 pacientes (58,1%); 133 fueron ME (24,2%) y el 56,4% de ellos fueron donantes de órganos (n = 75). Edema y desviación de la línea media en la TAC y la evaluación previa por el coordinador de trasplantes se asociaron a ME. La LTSV se asoció a no evolución a ME. Nueve pacientes de menos de 80 años, sin contraindicaciones para donación y con un GCS ≤ 4 fueron limitados en los 4 primeros días y fallecieron en asistolia. CONCLUSIONES: La aplicación de LTSV es frecuente en el paciente neurocrítico. Casi la mitad de LTSV consistió en el no ingreso en unidades de críticos y, en ocasiones, sin evaluar su potencialidad como donante por la coordinación de trasplantes

OBJECTIVE: To analyze the profile, incidence of life support therapy limitation (LSTL) and donation potential in neurocritical patients. STUDY DESIGN: A multicenter prospective study was carried out. SETTING: Nine hospitals authorized for organ harvesting for transplantation. Patients: All patients consecutively admitted to the hospital with GCS < 8 during a 6-month period were followed-up until discharge or day 30 of hospital stay. STUDY VARIABLES: Demographic data, cause of coma, clinical status upon admission and outcome were analyzed. LSTL, brain death (BD) and organ donation incidence were recorded. RESULTS: A total of 549 patients were included, with a mean age of 59.0 ± 14.5 years. The cause of coma was cerebral hemorrhage in 27.0% of the cases.LSTL was applied in 176 patients (32.1%). In 78 cases LSTL consisted of avoiding ICU admission. Age, the presence of contraindications, and specific causes of coma were associated to LSTL. A total of 58.1% of the patients died (n=319). One-hundred and thirty-three developed BD (24.2%), and 56.4% of these became organ donors (n=75). The presence of edema and mid-line shift on the CT scan, and transplant coordinator evaluation were associated to BD. LSTL was associated to a no-BD outcome. Early LSTL (first 4 days) was applied in 9 patients under 80 years of age, with no medical contraindications for donation and a GCS ≤ 4 who finally died in asystole. CONCLUSIONS: LSTL is a frequent practice in neurocritical patients. In almost one-half of the cases, LSTL consisted of avoiding admission to the ICU, and on several occasions the donation potential was not evaluated by the transplant coordinator

Factores predictores de mortalidad en la sepsis urinaria con obstrucción ureteral / Mortality predictive factors in patients with urinary sepsis associated to upper urinary tract calculi

OBJETIVO: El objetivo de este estudio fue conocer las características clínicas de los pacientes con sepsis urológica obstructiva por litiasis ureteral que ingresaron en la Unidad de Cuidados Intensivos e identificar los factores predictores de mortalidad en las primeras 24 horas del ingreso. DISEÑO: Estudio observacional retrospectivo durante un periodo de 16 años (1996-2011). ÁMBITO: Unidad de Cuidados Intensivos polivalente de 20 camas de un hospital universitario de 2.° nivel. PACIENTES: Todos los pacientes que ingresaron en Unidad de Cuidados Intensivos por sepsis urológica obstructiva. INTERVENCIONES: Ninguna. VARIABLES DE INTERÉS PRINCIPALES: Variables clínicas y analíticas generales y relacionadas con el proceso urológico. Método diagnóstico, técnica desobstructiva, germen aislado y tratamiento. Análisis de factores de riesgo mediante regresión logística múltiple. RESULTADOS: Ciento siete pacientes ingresados con una mortalidad del 19,6%. El diagnóstico fue mayoritariamente por ecografía y la técnica descompresiva más utilizada fue la colocación de catéter ureteral doble J. Se aisló germen en el 48,6% de los pacientes. El 20,6% presentaron bacteriemia. En el análisis multivariante, la edad, el fallo renal agudo y el uso de drogas vasoactivas en las primeras 24 horas del ingreso se relacionaron de forma independiente con la mortalidad. CONCLUSIONES: La edad avanzada, el fallo renal agudo y la necesidad de fármacos vasoactivos se relacionaron con un aumento de riesgo de mortalidad en los pacientes con urosepsis secundaria a litiasis ureteral

PURPOSE: The aims of this study were to determine the clinical characteristics of patients with urinary sepsis associated to ureteral calculi admitted to the Intensive Care Unit (ICU), and to identify predictors of mortality in the first 24 hours of admission. DESIGN: A retrospective observational study covering a 16-year period (2006-2011) was carried out. SETTING: The combined clinical/surgical ICU of a secondary-level University hospital. PATIENTS: All patients admitted to the ICU due to obstructive urinary sepsis. INTERVENTIONS: None. MAIN VARIABLES: We analyzed general clinical and laboratory test and urological data. The diagnostic technique, affected side, decompression technique, isolated microorganism and antibiotic therapy used were also considered. The assessment of risk factors was performed by multiple logistic regression analysis. RESULTS: A total of 107 patients admitted to the ICU were included in the study, with a mortality rate of 19.6%. The diagnosis was mainly established by ultrasound, and the most commonly used decompression technique was retrograde JJ stenting. Microorganisms were isolated in 48.6% of the patients. In total, 20.6% of the patients had bacteremia. Multivariate analysis found age, acute renal failure and the use of vasoactive drugs administered continuously for the first 24hours of admission to be independently associated to mortality. CONCLUSIONS: Advanced age, acute renal failure and the need for vasoactive drugs were associated to an increased risk of mortality in patients with urinary sepsis associated to upper urinary tract calculi

Insertion of exogenous epitopes in the E3-19K of oncolytic adenoviruses to enhance TAP-independent presentation and immunogenicity.

Oncolytic adenoviruses can promote immune responses against tumors by expressing and/or displaying tumor-associated antigens. However, the strong immunodominance of viral antigens mask responses against tumor epitopes. In addition, defects in major histocompatibility complex class I antigen presentation pathway such as the downregulation of the transporter-associated with antigen processing (TAP) are frequently associated with immune evasion of tumor cells. To promote the immunogenicity of exogenous epitopes in the context of an oncolytic adenovirus, we have taken advantage of the ER localization of the viral protein E3-19K. We have inserted tumor-associated epitopes after the N-terminal signal sequence for membrane insertion of this protein and flanked them with linkers cleavable by the protease furin to facilitate their TAP-independent presentation. This strategy allowed an enhanced presentation of the exogenous epitopes in TAP-deficient tumor cells in vitro and the generation of higher specific immune responses in vivo that were able to significantly control tumor growth.

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)

Brain death organ donation potential and life support therapy limitation in neurocritical patients.

OBJECTIVE: To analyze the profile, incidence of life support therapy limitation (LSTL) and donation potential in neurocritical patients. STUDY DESIGN: A multicenter prospective study was carried out. SETTING: Nine hospitals authorized for organ harvesting for transplantation. PATIENTS: All patients consecutively admitted to the hospital with GCS < 8 during a 6-month period were followed-up until discharge or day 30 of hospital stay. STUDY VARIABLES: Demographic data, cause of coma, clinical status upon admission and outcome were analyzed. LSTL, brain death (BD) and organ donation incidence were recorded. RESULTS: A total of 549 patients were included, with a mean age of 59.0 ± 14.5 years. The cause of coma was cerebral hemorrhage in 27.0% of the cases.LSTL was applied in 176 patients (32.1%). In 78 cases LSTL consisted of avoiding ICU admission. Age, the presence of contraindications, and specific causes of coma were associated to LSTL. A total of 58.1% of the patients died (n=319). One-hundred and thirty-three developed BD (24.2%), and 56.4% of these became organ donors (n=75). The presence of edema and mid-line shift on the CT scan, and transplant coordinator evaluation were associated to BD. LSTL was associated to a no-BD outcome. Early LSTL (first 4 days) was applied in 9 patients under 80 years of age, with no medical contraindications for donation and a GCS ≤ 4 who finally died in asystole. CONCLUSIONS: LSTL is a frequent practice in neurocritical patients. In almost one-half of the cases, LSTL consisted of avoiding admission to the ICU, and on several occasions the donation potential was not evaluated by the transplant coordinator.

[Mortality predictive factors in patients with urinary sepsis associated to upper urinary tract calculi]. / Factores predictores de mortalidad en la sepsis urinaria con obstrucción ureteral.

PURPOSE: The aims of this study were to determine the clinical characteristics of patients with urinary sepsis associated to ureteral calculi admitted to the Intensive Care Unit (ICU), and to identify predictors of mortality in the first 24 hours of admission. DESIGN: A retrospective observational study covering a 16-year period (2006-2011) was carried out. SETTING: The combined clinical/surgical ICU of a secondary-level University hospital. PATIENTS: All patients admitted to the ICU due to obstructive urinary sepsis. INTERVENTIONS: None. MAIN VARIABLES: We analyzed general clinical and laboratory test and urological data. The diagnostic technique, affected side, decompression technique, isolated microorganism and antibiotic therapy used were also considered. The assessment of risk factors was performed by multiple logistic regression analysis. RESULTS: A total of 107 patients admitted to the ICU were included in the study, with a mortality rate of 19.6%. The diagnosis was mainly established by ultrasound, and the most commonly used decompression technique was retrograde JJ stenting. Microorganisms were isolated in 48.6% of the patients. In total, 20.6% of the patients had bacteremia. Multivariate analysis found age, acute renal failure and the use of vasoactive drugs administered continuously for the first 24 hours of admission to be independently associated to mortality. CONCLUSIONS: Advanced age, acute renal failure and the need for vasoactive drugs were associated to an increased risk of mortality in patients with urinary sepsis associated to upper urinary tract calculi.

[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.

Potencialidad de donación de órganos en muerte encefálica y limitación del tratamiento de soporte vital en los pacientes neurocríticos / Potential of organ donation in brain death and limitation of life support treatment in neurocritical patients

Objetivo. Analizar el perfil, la incidencia de limitaciónde tratamiento de soporte vital (LTSV) y la potencialidad de donación de órganos enpacientes neurocríticos. Diseño Multicéntrico prospectivo. Ámbito Nueve centros autorizados para extracción de órganos para trasplante...

Cross-cultural validation of the Children's Assessment of Participation and Enjoyment (CAPE) in Spain.

BACKGROUND: Despite growing interest in the topic of participation, the construct has not yet been assessed in children and adolescents with and without cerebral palsy (CP) in Spain. As there are no available instruments to measure participation in leisure activities which have been adapted in this country, the goal of this study was to validate a Spanish version of the Children's Assessment of Participation and Enjoyment (CAPE). METHOD: The sample comprised 199 children and adolescents with CP and 199 without CP, between 8 and 18 years of age, from seven regions in Spain. The adaptation of the original version of CAPE was carried out through translation and backward translation, and the validity of the instrument was analysed. Construct validity was assessed through the correlation of the diverse CAPE domains and the quality of life domains (KIDSCREEN questionnaire). Discriminant validity was established by comparing children and adolescents with CP and typically developing children and adolescents. For test-retest reliability, the children and adolescents with and without CP completed the CAPE questionnaire twice within 4 weeks. RESULTS: The correlations found between the CAPE domains and the quality of life domains show that the CAPE presents construct validity. The CAPE discriminated children and adolescents with CP from those without any disability in the results of participation. According to most CAPE domains, typically developing children and adolescents engage in a greater number of activities than children and adolescents with CP. Test-retest reliability for the Spanish version of CAPE was adequate. CONCLUSION: The study provides a valid instrument to assess the participation of children and adolescents with and without CP who live in Spain.