Identification of IL-6 Signalling Components as Predictors of Severity and Outcome in COVID-19

IL-6 is one of the major mediators of the hyper-inflammatory responses with complex biological functions as it can signal via different modes of action. IL-6 by classical signalling has anti-inflammatory and antibacterial activities, while trans-signalling mediates pro-inflammatory effects. The net biological effect of IL-6 is established by multiple factors beyond its absolute concentration. Here, we assess the relationship between IL-6 signalling variables [IL-6, soluble IL-6R (sIL-6R) and soluble gp130 (sgp130)] and outcomes in a cohort of 366 COVID-19 patients. The potential trans-signalling was evaluated by a ratio between the pro-inflammatory binary IL-6:sIL-6R complex and the inactive ternary IL-6:sIL-6R:sgp130 complex (binary/ternary complex) and the fold molar excess of sgp130 over sIL-6R (FME). Our data provide new evidence that high levels of IL-6, sIL-6R, sgp130, binary/ternary complex ratio, and low FME are independent predictors of COVID-19 severity in survivor patients (without death), and the combination of IL-6 + sIL-6R + sgp130 exhibited the most robust classification capacity. Conversely, in a subgroup of patients with a very poor prognosis, we found that high levels of IL-6 and low levels of sIL-6R, sgp130, and binary/ternary complex ratio were predictors of death. In this context, the highest predictive capacity corresponded to the combined analysis of IL-6 + FME + lymphopenia + creatinine. Herein, we present IL-6 signalling variables as a helpful tool for the early identification and stratification of patients with clear implications for treatment and clinical decision-making.The research work was supported by the Spanish Institute of Health Carlos III (COV-20/00792) and by the European Commission - NextgenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global). MAR-H acknowledges support from the Spanish Institute of Health Carlos III and the European Commission - NextgenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global). DC is supported by a predoctoral iPFIS (IFI 19/00048) funded by Spanish Institute of Health Carlos III. MN-N is supported by the Rio Hortega contract (CM20/00074)

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

COVID-19 vaccine failure

COVID-19 affects the population unequally with a higher impact on aged and immunosuppressed people. Hence, we assessed the effect of SARS-CoV-2 vaccination in immune compromised patients (older adults and oncohematologic patients), compared with healthy counterparts. While the acquired humoral and cellular memory did not predict subsequent infection 18 months after full immunization, spectral and computational cytometry revealed several subsets within the CD8+ T-cells, B-cells, NK cells, monocytes and CD45RA+ CCR7- Tγδ cells differentially expressed in further infected and non-infected individuals not just following immunization, but also prior to that. Of note, up to 7 subsets were found within the CD45RA+ CCR7- Tγδ population with some of them being expanded and other decreased in subsequently infected individuals. Moreover, some of these subsets also predicted COVID-induced hospitalization in oncohematologic patients. Therefore, we hereby have identified several cellular subsets that, even before vaccination, strongly related to COVID-19 vulnerability as opposed to the acquisition of cellular and/or humoral memory following vaccination with SARS-CoV2 mRNA vaccines.This study has been funded through Programa Estratégico Instituto de Biología y Genética Molecular (IBGM Junta de Castilla y León. Ref. CCVC8485), Junta de Castilla y León (Proyectos COVID 07.04.467B04.74011.0) and the European Commission – NextGenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global; SGL21-03-026 and SGL2021-03-038)N

Analgesia postoperatoria en la queiloplastia del lactante. Estudio comparativo: bloqueo infraorbitario intraoral bilateral con bupivacaína 0,25% con adrenalina vs. analgesia intravenosa con tramadol

Objective: To compare the effectiveness and length of bilateral intraoral blockade of the infraorbitary nerve versus standard intravenous analgesia with tramadol for the management of postoperative pain in breast-fed infants undergoing chieloplasty due to harelip. Material and methods: After conducting an adequate pre-anesthetic assessment and obtaining the informed consent from their parents, we performed a double-blind, randomized, controlled and randomized study in 25 ASA I infants with ages ranging from 3 to 10 months that were candidates to corrective harelip surgery (chieloplasty). All of them were pretreated half an hour before the surgical procedure with oral midazolan (0.5 mg.kg-1) and the same anesthesiologist performed the anesthetic technique and the nerve blockade in all the cases, this being inhaled induction with sevoflurane prior to venoclysis. General anesthesia was achieved with intravenous administration of atropine, fentanyl and rocuronium at the standard doses prior to endotracheal intubation and mechanical ventilation. Patients were randomized to one of the following groups: Group A (n = 12): 1-2 ml of bupivacaine 0.25% plus adrenaline was administered for bilateral blockade of the intraorbitary nerve and intravenous saline solution instead of intravenous analgesia with tramadol. Group B (n = 13): saline solution was administered for nerve blockade, instead of bupivacaine, and intravenous tramadol (1.5 mg.kg-1) was provided as postoperative analgesia. All of the patients underwent general anesthesia with sevoflurane and fentanyl "on-demand" according to standard parameters (blood pressure, heart rate, pupil size, etc.). During the first six hours at Reanimation, length of analgesia, degree of discomfort and pain severity were assessed. The presence of complications or side effects was also recorded. Data were analyzed using the t Student and the χ² test. Results: No differences were found regarding demographic features. Analgesia lasted more in group A (7.3 ± 5.1 h) compared to group B (2.8 ± 2.2 h) (p < 0.01). Subjective assessment of pain severity was higher in group B (2.23 ± 0.83) compared to group A (0.66 ± 0.6) (p < 0.01). Degree of comfort, as assessed through an objective scale, was significantly greater in the group undergoing blockade with local anesthetic. Discussion: Anesthesia for neonates undergoing surgical reparation of harelip with intraoral bilateral blockade of the infraorbitary nerve is a safe, simple and quick technique that provides a lasting postoperative analgesia and also reduces the risks of respiratory depression, since it allows a lower use of opiate analgesics and, hence, an immediate and comfortable awakening.Objetivo: Comparar la eficacia y duración del bloqueo del nervio infraorbitario intraoral bilateral frente a la analgesia intravenosa convencional con tramadol en el control del dolor postoperatorio en lactantes sometidos a queiloplastia por labio leporino. Material y métodos: Tras la realización de una adecuada valoración preanestésica y la obtención del consentimiento informado de los padres, realizamos un estudio prospectivo, controlado aleatorizado y doble ciego en 25 niños, ASA I, con edades comprendidas entre los 3-10 meses, tras obtener el consentimiento informado de los padres, propuestos para cirugía correctora de labio leporino (queiloplastia). Todos ellos fueron premeditados, media hora antes de la intervención quirúrgica, con midazolan oral (0,5 mg.kg-1) y, en todos los casos, se practicó la técnica anestésica y el bloqueo nervioso por el mismo anestesiólogo, que consistió en una inducción inhalatoria con sevoflurano previa a la venoclisis. La anestesia general se completó con atropina, fentanilo y rocuronio a las dosis establecidas que se administraron, por vía intravenosa, previamente a la intubación endotraqueal y la ventilación mecánica. Los pacientes fueron divididos aleatoriamente en dos grupos: Grupo A (n = 12): se administró 1-2 ml de bupivacaína al 0,25% con adrenalina para el bloqueo infraorbitario bilateral y solución salina intravenosa como sustitutivo de la analgesia intravenosa con tramadol. Grupo B (n = 13): se administró solución salina para el bloqueo nervioso, en lugar de la bupivacaína, y tramadol intravenoso (1,5 mg.kg-1) como analgesia postoperatoria. En todos ellos se realizó anestesia general con sevoflurano y fentanilo "a demanda" según parámetros convencionales (tensión arterial, frecuencia cardiaca, tamaño pupilar, etc.). Durante sus primeras seis horas de estancia en Reanimación se valoró la duración de la analgesia, grado de disconfort e intensidad dolorosa. Además se anotó la aparición de cualquier complicación o efecto adverso. Los datos se analizaron mediante t Student y test χ². Resultados: No existieron diferencias en cuanto a las características demográficas. La duración de la analgesia fue mayor en el grupo A (7,3 ± 5,1 h) que en el grupo B (2,8 ± 2,2 h) (p < 0,01). La valoración subjetiva de la intensidad dolorosa fue mayor en el grupo B (2,23 ± 0,83) que en el grupo A (0,66 ± 0,6) (p < 0,01). El grado de confort, según escala objetiva, fue significativamente mayor en el grupo que recibió el bloqueo con anestésico local. Discusión: La anestesia para neonatos sometidos a reparación de labio leporino, empleando bloqueo bilateral intraoral del nervio infraorbitario es una técnica segura, simple y rápida, que permite una analgesia duradera en el postoperatorio a la vez que minimiza los riesgos de depresión respiratoria, ya que posibilita una reducción en la utilización de analgésicos opioides, permitiendo un inmediato y confortable despertar

Identification of IL-6 Signalling Components as Predictors of Severity and Outcome in COVID-19

The research work was supported by the Spanish Institute of Health Carlos III (COV-20/00792) and by the European Commission - NextgenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global). MAR-H acknowledges support from the Spanish Institute of Health Carlos III and the European Commission - NextgenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global). DC is supported by a predoctoral iPFIS (IFI 19/00048) funded by Spanish Institute of Health Carlos III. MN-N is supported by the Rio Hortega contract (CM20/00074).IL-6 is one of the major mediators of the hyper-inflammatory responses with complex biological functions as it can signal via different modes of action. IL-6 by classical signalling has anti-inflammatory and antibacterial activities, while trans-signalling mediates proinflammatory effects. The net biological effect of IL-6 is established by multiple factors beyond its absolute concentration. Here, we assess the relationship between IL-6 signalling variables [IL-6, soluble IL-6R (sIL-6R) and soluble gp130 (sgp130)] and outcomes in a cohort of 366 COVID-19 patients. The potential trans-signalling was evaluated by a ratio between the pro-inflammatory binary IL-6:sIL-6R complex and the inactive ternary IL-6:sIL-6R:sgp130 complex (binary/ternary complex) and the fold molar excess of sgp130 over sIL-6R (FME). Our data provide new evidence that high levels of IL- 6, sIL-6R, sgp130, binary/ternary complex ratio, and low FME are independent predictors of COVID-19 severity in survivor patients (without death), and the combination of IL-6 + sIL-6R + sgp130 exhibited the most robust classification capacity. Conversely, in a subgroup of patients with a very poor prognosis, we found that high levels of IL-6 and low levels of sIL-6R, sgp130, and binary/ternary complex ratio were predictors of death. In this context, the highest predictive capacity corresponded to the combined analysis of IL-6 + FME + lymphopenia + creatinine. Herein, we present IL-6 signalling variables as a helpful tool for the early identification and stratification of patients with clear implications for treatment and clinical decision-making.Spanish Institute of Health Carlos III (COV-20/00792)European Commission - NextgenerationEU (Regulation EU 2020/2094)CSIC's Global Health Platform (PTI Salud Global)Spanish Institute of Health Carlos III and the European Commission - NextgenerationEU (Regulation EU 2020/2094)iPFIS (IFI 19/00048) funded by Spanish Institute of Health Carlos IIIRio Hortega contract (CM20/00074

Atención al paciente quirúrgico : proceso asistencial integrado

Publicado en la página web de la Consejería de Igualdad, Salud y Políticas Sociales: www.juntadeandalucia.es/salud (Consejería de Salud / Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados)En diciembre de 2015 se ha publicado: Manejo perioperatorio de medicación crónica : documento de apoyo al PAI atención al paciente quirúrgico (http://hdl.handle.net/10668/2135)YesEste proceso surge de la transformación de un Proceso Asistencial de Soporte en uno Asistencial Integrado. En él se describe desde la indicación quirúrgica hasta el alta, independientemente de la prioridad de la intervención. Y se aborda el proceso quirúrgico desde el prisma de la seguridad clínica en el entorno quirúrgico para garantizar la seguridad de nuestros pacientes frente a errores que causen morbilidad y/o mortalidad evitables. Se ha incorporado igualmente, la atención integral al dolor como dimensión transversal en todo su recorrido, ampliando la visión tradicional reactiva y limitada al postoperatorio a un enfoque preventivo desde el comienzo del proceso. Los cuidados de enfermería, estando presentes en las distintas etapas del recorrido del paciente, así como la estrategia de Uso Racional y Adecuado del Medicamento como dimensión transversal a todo el proceso

Juntas / Juntes

Multitud d'autores i autors aporten píndoles de microliteratura, de gèneres diversos, al tercer volum amb què l'Institut Universitari d'Estudis Feministes i de Gènere Purificación Escribano vol respondre al desafiament per l'eradicació de la violència contra les dones.Tercer desafío por la erradicación de la violencia contra las mujeres del Institut Universitari d'Estudis Feministes i de Gènere Purificación Escribano de la Universitat Jaume I a través de microliteratura