Ecografía pulmonar en final de vida en domicilio: una nueva aproximación diagnóstica para un conocimiento de la fisiopatología del morir. Serie de casos / At-home lung ultrasound at the end of life: a new diagnostic approach to understand the pathophysiology of death. A case series

Introducción: La ecografía pulmonar aún no se ha utilizado para conocer el estado del pulmón, y su evolución, en una enfermedad terminal. El objetivo de este trabajo es entender cómo se comporta el pulmón en final de vida usando la “ecografía en el punto de atención” en el domicilio y demostrar los beneficios que para el enfermo, entorno y medicina paliativa tendrá este procedimiento. El ecógrafo empleado es digital y lo conforma la propia sonda con un peso de 313 g y unas medi- das de 185 × 56 × 35 mm, al que se acopla un dispositivo con una pantalla de dimensión variable, fácil de portar. Se realizó una exploración sistemática, en modo bidimensional, de 4 puntos en cada hemitórax y 3 vistas cardiacas. Pacientes y métodos: Estudio observacional de 7 pacientes derivados, entre mayo y julio de 2020, al equipo de cuidados paliativos y que fallecieron en su domicilio en las 72 h posteriores a la eco- grafía: 2 sufrían cáncer, uno enfermedad de Parkinson y 4 no presentaban causa clara de muerte. Resultados: La pleura estaba alterada en los pacientes con cáncer en los que se objetivaba un derrame pleural en diferente cuantía y también pericárdico en uno de ellos, con una edematiza- ción variable del parénquima pulmonar; en 3 de ellos se objetivó, además, una función ventricu- lar reducida. El enfermo de Parkinson tenía un pulmón aireado pero sin capacidad inspiratoria. Discusión: La ecografía pulmonar ofrece información relevante para los profesionales al mejorar la capacidad diagnóstica en final de vida y las causas de muerte, identifica derrames pleurales y pericárdicos, y posibilitará optimizar decisiones terapéuticas. (AU)

Introduction: Pulmonary ultrasound has not yet been used to determine the state of the lung and its evolution in the course of terminal illness. The objective of this work is to assess how the lung behaves in people at the end of life using “point of care ultrasound” at home, and to detect the benefits that this procedure will have for the patient, the family, and the future of palliative medicine. The ultrasound machine used is a digital one comprised of the probe itself, weighing 313 g and measuring 185 × 56 × 35 mm, attached to a device with a variable-size screen that is easy to carry. A systematic examination in 2-dimensional mode of four points was made in each hemi- thorax, including three cardiac views. Patients and methods: Observational study sample of seven patients referred between May and July 2020 to our home palliative care team, and who died within 72 hours after undergoing lung ultrasound: 2 with cancer, another one with Parkinson’s disease, and 4 without a clear cause of death. Results: The pleural line was altered in all cancer patients, who also had pleural effusion, while another one had pericardial effusion with variable edema of the lung parenchyma; 3 of them had reduced ventricular function. The Parkinson’s disease patient had a normal aerated lung but significant respiratory dysfunction. Discussion: Lung ultrasound offers relevant information for professionals by improving diagnostic capacity at the end of life, and on causes of death; it identifies pleural and pericardial effusions, and will make it possible to optimize therapeutic decision-making. (AU)

SGnn: A Web Server for the Prediction of Prion-Like Domains Recruitment to Stress Granules Upon Heat Stress.

Proteins bearing prion-like domains (PrLDs) are essential players in stress granules (SG) assembly. Analysis of data on heat stress-induced recruitment of yeast PrLDs to SG suggests that this propensity might be connected with three defined protein biophysical features: aggregation propensity, net charge, and the presence of free cysteines. These three properties can be read directly in the PrLDs sequences, and their combination allows to predict protein recruitment to SG under heat stress. On this basis, we implemented SGnn, an online predictor of SG recruitment that exploits a feed-forward neural network for high accuracy classification of the assembly behavior of PrLDs. The simplicity and precision of our strategy should allow its implementation to identify heat stress-induced SG-forming proteins in complete proteomes.

DispHred: A Server to Predict pH-Dependent Order-Disorder Transitions in Intrinsically Disordered Proteins.

The natively unfolded nature of intrinsically disordered proteins (IDPs) relies on several physicochemical principles, of which the balance between a low sequence hydrophobicity and a high net charge appears to be critical. Under this premise, it is well-known that disordered proteins populate a defined region of the charge-hydropathy (C-H) space and that a linear boundary condition is sufficient to distinguish between folded and disordered proteins, an approach widely applied for the prediction of protein disorder. Nevertheless, it is evident that the C-H relation of a protein is not unalterable but can be modulated by factors extrinsic to its sequence. Here, we applied a C-H-based analysis to develop a computational approach that evaluates sequence disorder as a function of pH, assuming that both protein net charge and hydrophobicity are dependent on pH solution. On that basis, we developed DispHred, the first pH-dependent predictor of protein disorder. Despite its simplicity, DispHred displays very high accuracy in identifying pH-induced order/disorder protein transitions. DispHred might be useful for diverse applications, from the analysis of conditionally disordered segments to the synthetic design of disorder tags for biotechnological applications. Importantly, since many disorder predictors use hydrophobicity as an input, the here developed framework can be implemented in other state-of-the-art algorithms.

pH-Dependent Aggregation in Intrinsically Disordered Proteins Is Determined by Charge and Lipophilicity.

Protein aggregation is associated with an increasing number of human disorders and premature aging. Moreover, it is a central concern in the manufacturing of recombinant proteins for biotechnological and therapeutic applications. Nevertheless, the unique architecture of protein aggregates is also exploited by nature for functional purposes, from bacteria to humans. The relevance of this process in health and disease has boosted the interest in understanding and controlling aggregation, with the concomitant development of a myriad of algorithms aimed to predict aggregation propensities. However, most of these programs are blind to the protein environment and, in particular, to the influence of the pH. Here, we developed an empirical equation to model the pH-dependent aggregation of intrinsically disordered proteins (IDPs) based on the assumption that both the global protein charge and lipophilicity depend on the solution pH. Upon its parametrization with a model IDP, this simple phenomenological approach showed unprecedented accuracy in predicting the dependence of the aggregation of both pathogenic and functional amyloidogenic IDPs on the pH. The algorithm might be useful for diverse applications, from large-scale analysis of IDPs aggregation properties to the design of novel reversible nanofibrillar materials.

Morphine infusor pump switch to oral methadone.

Between 2014 and 2017, four patients with widespread cancer were referred to a home palliative care team from a hospital in Oviedo (Spain) with subcutaneous elastomeric infusion pump containing 180-260 mg/day of morphine for previously uncontrolled pain. 3-4 rotations were performed over 5-11 days, gradually substituting morphine for oral methadone (three times a day) to minimise the risks of rapid conversion, with a highly variable final subcutaneous morphine:oral methadone ratio (5:1 to 17:1), guided by the absence of pain, and to enhance the patient's functional capacity avoiding device dependence. The final methadone dose varied between 15 and 39 mg/day. There was daily telephone supervision and visits every 2-4 days. Patient demise occurred 56, 111, 168 and 350 days following the opioid conversion, and methadone was maintained until then. In all cases and prior to concluding the rotation, pain was controlled and sleepiness had subsided.

¿Debemos preocuparnos por desactivar marcapasos y desfibriladores en final de vida? / Should we take care to deactivate pacemakers and defibrillators at the end of life?

El artículo reflexiona sobre los dispositivos cardiacos implantables, fundamentalmente los marcapasos sin perder de referencia los desfibriladores, y su repercusión en la agonía del/de la paciente en final de vida portador/a de estos dispositivos

This article considers implantable cardiac devices, primarily pacemakers, but also defibrillators, and their impact the agony of patients carrying these devices at the end of life