Cytogenomic characterization of small supernumerary marker chromosomes in patients with pigmentary mosaicism.

Introduction: The combination of gene content on the marker chromosome, chromosomal origin, level of mosaicism, origin mechanism (chromothripsis), and uniparental disomy can influence the final characterization of sSMCs. Several chromosomal aberrations, including sSMCs, have been observed in 30%-60% of patients with pigmentary mosaicism, and in more than 80%, chromosomal abnormalities are present in the mosaic state. In patients with pigmentary mosaicism the most representative chromosomes involved in sSMCs are 3, 5, 6, 9, 10, 13, 15, 18, 20, and X. In this study, we included the complete clinical, cytogenetic, and molecular characterization of seven patients with pigmentary mosaicism associated with the presence of SMCs of different chromosomal origins. Methods: The patients were diagnosed by the Genetics and Dermatology Department of three different hospitals. Cytogenetic and FISH analyses were performed on peripheral blood, light skin, and dark skin. FISH analysis was performed using different probes, depending on the marker chromosome description. Different array analysis was performed. Results: To date, of the seven cases studied, the chromosomal origins of six were successfully identified by FISH or array analysis. The chromosomes involved in SMCs were 6, 9, 15, and 18, X. The most frequently found was the centric minute structure. Discussion: To date, this group of seven patients constitutes the largest clinical and cytogenetically finely described study of cases with pigmentary mosaicism associated with sSMCs. Undoubtedly, analysis of the two skin types is a fundamental part of our study, as numerical differences may occur in the cell lines found in each skin type. The knowledge generated in this study will help delineate a very heterogeneous entity more accurately, and in the future, analyzing more patients with PM will likely establish a more definite association with the presence of this genetic alteration.

Estrategias de analgesia, sedación, delirium y confort individualizado en el enfermo crítico: Una revisión narrativa / Individualised analgesia, sedation, delirium and comfort management strategies in the ICU: a narrative review

Este grupo es producto del acuerdo de colaboración firmado por la Sociedad de Medicina Intensiva de Madrid (SOMIAMA) y la Sociedad de Anestesiología, Reanimación y Terapéutica del Dolor de Madrid (SAR MADRID), por el que las organizaciones acordaron crear grupos de trabajo conjuntos para mejorar la atención al paciente crítico.El dolor, el malestar, la agitación y el delirio causan sufrimiento, retrasan el alta y pueden provocar complicaciones graves en los pacientes ingresados en las unidades de cuidados críticos médicos y quirúrgicos y en las unidades de cuidados postanestésicos. Los principales objetivos en este tipo de unidades incluyen: asegurar el confort de los pacientes que sufren o se recuperan de una enfermedad crítica. Evitar las complicaciones asociadas a las medidas, sobre todo farmacológicas, adoptadas para asegurar ese confort. (AU)

This group is a product of the collaboration agreement signed by Sociedad de Medicina Intensiva de Madrid (SOMIAMA) and Sociedad de Anestesiología, Reanimación y Terapéutica del Dolor de Madrid (SAR MADRID), under which the organisations agreed to create joint working groups to improve critical patient care.Pain, discomfort, agitation, and delirium cause suffering, delay discharge, and can lead to serious complications in patients admitted to medical and surgical critical care units and post-anaesthesia care units. The main objectives in this type of unit include: Ensuring the comfort of patients suffering or recovering from a critical illness. Avoiding complications associated with the measures, particularly pharmacological, taken to ensure that comfort. (AU)

Individualised analgesia, sedation, delirium and comfort management strategies in the ICU: a narrative review.

This group is a product of the collaboration agreement signed by SOMIAMA (Sociedad de Medicina Intensiva de Madrid) and SAR MADRID (Sociedad de Anestesiología, Reanimación y Terapéutica del Dolor de Madrid) under which the organisations agreed to create joint working groups to improve critical patient care. Pain, discomfort, agitation, and delirium cause suffering, delay discharge, and can lead to serious complications in patients admitted to medical and surgical critical care units and post-anaesthesia care units. The main objectives in this type of unit include: Ensuring the comfort of patients suffering or recovering from a critical illness.Avoiding complications associated with the measures, particularly pharmacological, taken to ensure that comfort.

Determinants of mortality in cancer patients with unscheduled admission to the Intensive Care Unit: A prospective multicenter study / Factores determinantes de la mortalidad en pacientes con cáncer ingresados de forma no programada en la Unidad de Cuidados Intensivos: estudio multicéntrico prospectivo

Objectives To analyze clinical fatures associated to mortality in oncological patients with unplanned admission to the Intensive Care Unit (ICU), and to determine whether such risk factors differ between patients with solid tumors and those with hematological malignancies. Design An observational study was carried out. Setting A total of 123 Intensive Care Units across Spain. Patient All cancer patients with unscheduled admission due to acute illness related to the background oncological disease. Interventions None. Main variables Demographic parameters, severity scores and clinical condition were assessed, and mortality was analyzed. Multivariate binary logistic regression analysis was performed. Results A total of 482 patients were included: solid cancer (n=311) and hematological malignancy (n=171). Multivariate regression analysis showed the factors independently associated to ICU mortality to be the APACHE II score (OR 1.102; 95% CI 1.064–1.143), medical admission (OR 3.587; 95% CI 1.327–9.701), lung cancer (OR 2.98; 95% CI 1.48–5.99) and mechanical ventilation after the first 24h of ICU stay (OR 2.27; 95% CI 1.09–4.73), whereas no need for mechanical ventilation was identified as a protective factor (OR 0.15; 95% CI 0.09–0.28). In solid cancer patients, the APACHE II score, medical admission, antibiotics in the previous 48h and lung cancer were identified as independent mortality indicators, while no need for mechanical ventilation was identified as a protective factor. In the multivariate analysis, the APACHE II score and mechanical ventilation after 24h of ICU stay were independently associated to mortality in hematological cancer patients, while no need for mechanical ventilation was identified as a protective factor. Neutropenia was not identified as an independent mortality predictor in either the total cohort or in the two subgroups (AU)

Objetivos Determinar las características clínicas asociadas con la mortalidad en pacientes oncológicos ingresados de forma no programada en la UCI. También evaluamos si estos factores de riesgos difieren en los pacientes con neoplasias hematológicas o tumores sólidos. Diseño Estudio observacional. Ámbito Ciento veintitrés Unidades de Cuidados Intensivos en España. Pacientes Todos los pacientes con cáncer ingresados de forma no programada debido a una enfermedad aguda asociada con la enfermedad oncológica. Intervenciones Ninguna. Variables principales Las variables analizadas fueron los datos demográficos, escalas pronósticas de gravedad y el estado clínico del paciente. Se analizó la mortalidad y los factores relacionados con ésta. Se aplicó un análisis de regresión logística binaria multivariante. Resultados Se incluyó a un total de 482 pacientes: con tumores sólidos (n=331) y con neoplasias hematológicas (n=171). En el análisis de regresión multivariante, los factores asociados de manera independiente con la mortalidad en la UCI fueron la puntuación APACHE II (OR 1,102; IC del 95% 1,064-1,143), el ingreso médico (OR 3,587; IC del 95% 1,327-9,701), el cáncer de pulmón (OR 2,98, IC del 95% 1,48-5,99) y la ventilación mecánica tras las primeras 24h de ingreso en la UCI (OR 2,27; IC del 95% 1,09-4,73), mientras que la no necesidad de ventilación mecánica fue un factor protector (OR 0,15; IC del 95% 0,09-0,28). En el caso de los tumores sólidos, la puntuación APACHE II, el ingreso médico, la administración de antibióticos en las 48 h previas y el cáncer de pulmón fueron variables independientes relacionadas con la mortalidad, y la no necesidad de ventilación mecánica se identificó como un factor protector. En el análisis multivariante, la puntuación APACHE II y la ventilación mecánica al cabo de 24h desde el ingreso en la UCI se asociaron de manera independiente con mortalidad en pacientes con neoplasias hematológicas (AU)

Determinants of mortality in cancer patients with unscheduled admission to the Intensive Care Unit: A prospective multicenter study.

OBJECTIVES: To analyze clinical features associated to mortality in oncological patients with unplanned admission to the Intensive Care Unit (ICU), and to determine whether such risk factors differ between patients with solid tumors and those with hematological malignancies. DESIGN: An observational study was carried out. SETTING: A total of 123 Intensive Care Units across Spain. PATIENTS: All cancer patients with unscheduled admission due to acute illness related to the background oncological disease. INTERVENTIONS: None. MAIN VARIABLES: Demographic parameters, severity scores and clinical condition were assessed, and mortality was analyzed. Multivariate binary logistic regression analysis was performed. RESULTS: A total of 482 patients were included: solid cancer (n=311) and hematological malignancy (n=171). Multivariate regression analysis showed the factors independently associated to ICU mortality to be the APACHE II score (OR 1.102; 95% CI 1.064-1.143), medical admission (OR 3.587; 95% CI 1.327-9.701), lung cancer (OR 2.98; 95% CI 1.48-5.99) and mechanical ventilation after the first 24h of ICU stay (OR 2.27; 95% CI 1.09-4.73), whereas no need for mechanical ventilation was identified as a protective factor (OR 0.15; 95% CI 0.09-0.28). In solid cancer patients, the APACHE II score, medical admission, antibiotics in the previous 48h and lung cancer were identified as independent mortality indicators, while no need for mechanical ventilation was identified as a protective factor. In the multivariate analysis, the APACHE II score and mechanical ventilation after 24h of ICU stay were independently associated to mortality in hematological cancer patients, while no need for mechanical ventilation was identified as a protective factor. Neutropenia was not identified as an independent mortality predictor in either the total cohort or in the two subgroups. CONCLUSIONS: The risk factors associated to mortality did not differ significantly between patients with solid cancers and those with hematological malignancies. Delayed intubation in patients requiring mechanical ventilation might be associated to ICU mortality.

Neuropsychological rehabilitation for post-COVID-19 syndrome: results of a clinical programme and six-month follow up.

INTRODUCTION: Patients with post-COVID-19 syndrome may present cognitive and emotional symptomatology. This study aims to analyse the results of an outpatient neuropsychological intervention programme for post-COVID-19 syndrome. METHOD: In June 2020 Institut Guttmann started an outpatient post-COVID-19 neurorehabilitation programme, including respiratory therapy, physiotherapy, and neuropsychological rehabilitation. Before and after the programme, the cognitive-emotional state of all participants is assessed. Six months after treatment, a follow-up assessment is administered (which includes a collection of information on various aspects of daily life). RESULTS: The sample analysed consisted of 123 patients (mean age: 51 years, SD: 12.41). Seventy-four per cent (n = 91) had cognitive impairment and underwent cognitive treatment (experimental group); the remaining 26% (n = 32) constituted the control group. After the intervention, the experimental group improved in working memory, verbal memory (learning, recall and recognition), verbal fluency and anxious-depressive symptomatology. The control group showed changes in immediate memory, verbal memory (learning and recognition) and depressive symptomatology, although the effect size in the latter two was smaller than in the experimental group. Six months after treatment, 44.9% of the patients were unable to perform their pre-COVID-19 work activity, and 81.2% reported difficulties in their activities of daily living. CONCLUSIONS: Neuropsychological rehabilitation is an effective tool to treat the cognitive-emotional deficits present in post-COVID-19 syndrome. However, months after the end of treatment, not all patients recover their pre-COVID-19 functional level.

Utilidad de la ECMO sobre el injerto pulmonar disfuncionante en un modelo porcino estandarizado de trasplante unipulmonar / [Usefulness of ECMO on dysfunctional lung graft in a standardized porcine model of one-lung transplant]

Objetivo: Establecer un modelo de muerte encefálica y trasplante pulmonar y analizar el posible papel protector del oxigenador de membrana extracorpóreo (ECMO).Métodos: Se emplearon 20 cerdos hembras, 10 donantes y 10 receptoras. Las receptoras del Grupo A (n = 5) fueron sometidas a un trasplante unipulmonar izquierdo (Tx-UPI) sin ECMO. Las receptoras del Grupo B (n = 5) se sometieron a un Tx-UPI con ECMO venoarterial (ECMO-VA). Se recopilaron datos funcionales e histológicos en situación basal, a los 10 minutos de clampar el hilio derecho (Tiempo 1) y a las 2 horas (Tiempo 2). Se analizó la expresión proteica de marcadores de inflamación y de la ruta de hipoxia.Resultados: El modelo de muerte encefálica empleado, seguido de un tiempo de isquemia frío prolongado (20 horas) dio lugar a la aparición de un edema pulmonar severo. Tras el implante, 3 receptores del grupo A sobrevivieron hasta el Tiempo 2, falleciendo 2 por edema pulmonar masivo. Por el contrario, todos los animales del Grupo B sobrevivieron, siendo la PaO2 en ese momento de 462,72 mmHg. Hubo un incremento de la expresión de IL6, TNF, PCR, AC IX y el VEGF, así como un descenso en la expresión de IL8 y GLUT1, al usar la ECMO.Conclusiones: Se ha desarrollado un modelo porcino estandarizado y reproducible de muerte encefálica, que simula el proceso clínico de la donación pulmonar. Este modelo puede servir de plataforma para investigar posibles dianas terapéuticas. (AU)

Objective: Establish a model of brain death and lung transplantation and analyze the possible protective role of extracorporeal membrane oxygenation (ECMO).Methods: 20 female pigs were used, 10 donors and 10 recipients. Group A recipients (n = 5) underwent left-sided single- lung transplantation (LUCT-Tx) without ECMO. Group B recipients (n = 5) underwent ICU-Tx with venoarterial ECMO (VA-ECMO). Functional and histological data were collected at baseline, 10 minutes after clamping the right hilum (Time 1) and 2 hours (Time 2). Protein expression of inflammation markers and the hypoxia pathway was analyzed.Results: The brain death model used, followed by a prolonged cold ischemia time (20 hours) gave rise to the appearance of severe pulmonary edema. After implantation, 3 group A recipients survived until Time 2, with 2 dying from massive pulmonary edema. In contrast, all the animals in Group B survived, with PaO2 at that time being 462.72 mmHg. There was an increase in the expression of IL6, TNFα, CRP, AC IX and VEGF, as well as a decrease in the expression of IL8 and GLUT1, when using ECMO.Conclusions: A standardized and reproducible porcine model of brain death has been developed, which simulates the clinical process of lung donation. This model can serve as a platform to investigate possible therapeutic targets. (AU)

[Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units]. / Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Influence of general anaesthesia on the intravenous acetaminophen pharmacokinetics in Beagle dogs.

OBJECTIVE: To determine if general anaesthesia influences the intravenous (IV) pharmacokinetics (PK) of acetaminophen in dogs. STUDY DESIGN: Prospective, crossover, randomized experimental study. ANIMALS: A group of nine healthy Beagle dogs. METHODS: Acetaminophen PK were determined in conscious and anaesthetized dogs on two separate occasions. Blood samples were collected before, and at 5, 10, 15, 30, 45, 60 and 90 minutes and 2, 3, 4, 6, 8, 12 and 24 hours after 20 mg kg-1 IV acetaminophen administration. Haematocrit, total proteins, albumin, alanine aminotransferase, aspartate aminotransferase, urea and creatinine were determined at baseline and 24 hours after acetaminophen. The anaesthetized group underwent general anaesthesia (90 minutes) for dental cleaning. After the administration of dexmedetomidine (3 µg kg-1) intramuscularly, anaesthesia was induced with propofol (2-3 mg kg-1) IV, followed by acetaminophen administration. Anaesthesia was maintained with isoflurane in 50% oxygen (Fe'Iso 1.3-1.5%). Dogs were mechanically ventilated. Plasma concentrations were analysed with high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling. A Wilcoxon test was used to compare PK data between groups, and clinical laboratory values between groups, and before versus 24 hours after acetaminophen administration. Data are presented as median and range (p < 0.05). RESULTS: A two-compartmental model best described time-concentration profiles of acetaminophen. No significant differences were found for volume of distribution values 1.41 (0.94-3.65) and 1.72 (0.89-2.60) L kg-1, clearance values 1.52 (0.71-2.30) and 1.60 (0.91-1.78) L kg-1 hour-1 or terminal elimination half-life values 2.45 (1.45-8.71) and 3.57 (1.96-6.35) hours between conscious and anaesthetized dogs, respectively. Clinical laboratory variables were within normal range. No adverse effects were recorded. CONCLUSIONS AND CLINICAL RELEVANCE: IV acetaminophen PK in healthy Beagle dogs were unaffected by general anaesthesia under the study conditions. Further studies are necessary to evaluate the PK in different clinical contexts.