The prognostic impact of SIGLEC5-induced impairment of CD8+ T cell activation in sepsis.

BACKGROUND: Sepsis is associated with T-cell exhaustion, which significantly reduces patient outcomes. Therefore, targeting of immune checkpoints (ICs) is deemed necessary for effective sepsis management. Here, we evaluated the role of SIGLEC5 as an IC ligand and explored its potential as a biomarker for sepsis. METHODS: In vitro and in vivo assays were conducted to both analyse SIGLEC5's role as an IC ligand, as well as assess its impact on survival in sepsis. A multicentre prospective cohort study was conducted to evaluate the plasmatic soluble SIGLEC5 (sSIGLEC5) as a mortality predictor in the first 60 days after admission in sepsis patients. Recruitment included sepsis patients (n = 346), controls with systemic inflammatory response syndrome (n = 80), aneurism (n = 11), stroke (n = 16), and healthy volunteers (HVs, n = 100). FINDINGS: SIGLEC5 expression on monocytes was increased by HIF1α and was higher in septic patients than in healthy volunteers after ex vivo LPS challenge. Furthermore, SIGLEC5-PSGL1 interaction inhibited CD8+ T-cell proliferation. Administration of sSIGLEC5r (0.8 mg/kg) had adverse effects in mouse endotoxemia models. Additionally, plasma sSIGLEC5 levels of septic patients were higher than HVs and ROC analysis revealed it as a mortality marker with an AUC of 0.713 (95% CI, 0.656-0.769; p < 0.0001). Kaplan-Meier survival curve showed a significant decrease in survival above the calculated cut-off (HR of 3.418, 95% CI, 2.380-4.907, p < 0.0001 by log-rank test) estimated by Youden Index (523.6 ng/mL). INTERPRETATION: SIGLEC5 displays the hallmarks of an IC ligand, and plasma levels of sSIGLEC5 have been linked with increased mortality in septic patients. FUNDING: Instituto de Salud Carlos III (ISCIII) and "Fondos FEDER" to ELC (PIE15/00065, PI18/00148, PI14/01234, PI21/00869), CDF (PI21/01178), RLR (FI19/00334) and JAO (CD21/00059).

Comparison of strategies for adherence to venous thromboembolism prophylaxis in high-risk surgical patients: a before and after intervention study.

BACKGROUND: Venous thromboembolism (VTE) is a major cause of perioperative morbimortality. Despite significant efforts to advance evidence-based practice, prevention rates remain inadequate in many centres. OBJECTIVE: To evaluate the effectiveness of different strategies aimed at improving adherence to adequate VTE prophylaxis in surgical patients at high risk of VTE. METHOD: Before and after intervention study conducted at a tertiary hospital. Adherence to adequate VTE prophylaxis was compared according to three strategies consecutively implemented from January 2019 to December 2020. A dedicated hospitalist physician alone (strategy A) or in conjunction with a nurse (strategy B) overlooked the postoperative period to ensure adherence and correct inadequacies. Finally, a multidisciplinary team approach (strategy C) focused on promoting adequate VTE prophylaxis across multiple stages of care-from the operating room (ie, preoperative team-based checklist) to collaboration with clinical pharmacists in the postoperative period-was implemented. RESULTS: We analysed 2074 surgical patients: 783 from January to June 2019 (strategy A), 669 from July 2019 to May 2020 (strategy B), and 622 from June to December 2020 (strategy C). VTE prophylaxis adherence rates for strategies (A), (B) and (C) were (median (25th-75th percentile)) 43.29% (31.82-51.69), 50% (42.57-55.80) and 92.31% (91.38-93.51), respectively (p<0.001; C>A=B). There was a significant reduction in non-compliance on all analysed criteria (risk stratification (A (25.5%), B (22%), C (6%)), medical documentation (A (68%), B (55.2%) C (9%)) and medical prescription (A (51.85%), B (48%), C (6.10%)) after implementation of strategy C (p<0.05). Additionally, a significant increase in compliance with adequate dosage, dosing interval and scheduling of the prophylactic regimen was observed. CONCLUSION: Perioperative VTE prophylaxis strategies that relied exclusively on physicians and/or nurses were associated with suboptimal execution and prevention. A multidisciplinary team-based approach that covers multiple stages of patient care significantly increased adherence to adequate VTE prophylaxis in surgical patients at high risk of developing perioperative VTE.

Traducir el pensamiento en acción: Interfaces cerebro-máquina y el problema ético de la agencia / Translating thought into action: brain-computer interfaces and the ethical problem of agency / Traduir el pensament en acció: Interfícies cervell-màquina i el problema ètic de l'agència

En este artículo, nos proponemos dos objetivos: el primero, describir la teoría clásica de la agencia intencional y cómo la neurotecnología de las interfaces cerebro-máquina desafía los requisitos de la teoría clásica de la agencia y de la consciencia corporal. La neurotecnología de las interfaces cerebro-máquina funciona implantando electrodos directamente en el área de la corteza motora del cerebro que controla el movimiento, y está diseñada para detectar las señales neuronales asociadas con la intención de moverse, que son después decodificadas por un algoritmo en un computador en tiempo real. Así, una persona podría pensar en mover su pierna o su brazo y la máquina recibiría la información de su pensamiento para traducir el pensamiento en acción, mediante prótesis internas o exoesqueletos. Esto es posible y sus aplicaciones se proyectan tanto sobre la rehabilitación de la funcionalidad motora, como sobre la posibilidad de mejoramiento (enhancement) de las capacidades humanas. Ambas aplicaciones dan lugar a numerosas implicaciones éticas, pero destacamos principalmente una, que denominamos: el problema ético de la agencia. El segundo objetivo del artículo es explorar brevemente la ética algorítmica en el contexto de las interfaces cerebro-máquina y cómo se entienden en este ámbito la autonomía, la responsabilidad y la privacidad informacional. Finalmente, abogamos por la necesidad de un marco ético de principios que regule la neurotecnología, y en tal sentido apelamos a los nuevos neuroderechos

The aim of this article is twofold: Firstly, we intend to describe the classical theory of intentional agency and to analyze how the neuro-technology of brain-machine interfaces (BCI) challenges the demands of that classical theory of agency and body consciousness. BCI neuro-technology works by implanting electrodes directly into the motor brain cortex that controls movement and detect neuronal signals associated with the intention to move, what is decoded by an algorithm on a computer in real time. Thus, someone could simply think about moving a leg or an arm and the tool (a prosthesis or exoskeleton) would receive the information to translate thought into action. This is yet feasible and its applications could involve rehabilitation of motor function and the possibility of enhancing human abilities. Both applications give rise to various several ethical implications but mainly to one that we call "the ethical problem of agency". Secondly, we briefly explore the ethics of algorithms in the context of BCI neuro-technology and the way autonomy, responsibility, and informational privacy are understood. Finally, we advocate the need for an ethical framework of principles governing neuro-technology, such as the new neuro-rights

En aquest article, ens proposem dos objectius: el primer, descriure la teoria clàssica de l'agència intencional i com la neurotecnologia de les interfícies cervell-màquina desafia els requisits de la teoria clàssica de l'agència i de la consciència corporal. La neurotecnologia de les interfícies cervell-màquina funciona implantant elèctrodes directament en l'àrea de l'escorça motora del cervell que controla el moviment, i està dissenyada per a detectar els senyals neuronals associades amb la intenció de moure's, que són després decodificades per un algoritme en un computador en temps real. Així, una persona podria pensar a moure la seva cama o el seu braç i la màquina rebria la informació del seu pensament per a traduir el pensament en acció, mitjançant pròtesis internes o exoesquelets. Això és possible i les seves aplicacions es projecten tant sobre la rehabilitació de la funcionalitat motora, com sobre la possibilitat de millorament (enhancement) de les capacitats humanes. Totes dues aplicacions donen lloc a nombroses implicacions ètiques, però destaquem principalment una, que denominem: el problema ètic de l'agència. El segon objectiu de l'article és explorar breument l'ètica algorítmica en el context de les interfícies cervell-màquina i com s'entenen en aquest àmbit l'autonomia, la responsabilitat i la privacitat informacional. Finalment, advoquem per la necessitat d'un marc ètic de principis que reguli la neurotecnologia, i en tal sentit apel·lem als nous neuro-drets

EPICO 3.0. Management of non-neutropenic patients in medical wards / EPICO 3.0. Tratamiento del paciente no neutropénico en la planta de medicina interna

Background. Although the management of invasive fungal infection (IFI) has improved, a number of controversies persist regarding the approach to invasive fungal infection in non-neutropenic medical ward patients. Aims. To identify the essential clinical knowledge to elaborate a set of recommendations with a high level of consensus necessary for the management of IFI in non-neutropenic medical ward patients. Methods. A prospective, Spanish questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all specialists (intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases) in IFI and belonging to six scientific national societies. They responded to five questions prepared by the coordination group after a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each category had to be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting held after extracting the recommendations from the chosen topics, and validated the pre-selected recommendations and derived algorithm. Results. The following recommendations were validated and included in the algorithm: 1. several elements were identified as risk factors for invasive candidiasis (IC) in non-hematologic medical patients; 2. no agreement on the use of the colonization index to decide whether prescribing an early antifungal treatment to stable patients (no shock), with sepsis and no other evident focus and IC risk factors; 3. agreement on the use of the Candida Score to decide whether prescribing early antifungal treatment to stable patients (no shock) with sepsis and no other evident focus and IC risk factors; 4. agreement on initiating early antifungal treatment in stable patients (no shock) with a colonization index>0.4, sepsis with no other evident focus and IC risk factors; 5. agreement on the performance of additional procedures in stable patients (no shock) with sepsis and no other evident focus, IC risk factors, without colonization index>0.4, but with a high degree of suspicion. Conclusions. Based on the expert's recommendations, an algorithm for the management of non-neutropenic medical patients was constructed and validated. This algorithm may be useful to support bedside prescription (AU)

Antecedentes. A pesar de que el manejo de la micosis invasiva ha mejorado, persisten ciertas controversias en su tratamiento en pacientes no neutropénicos. Objetivos. Identificar el conocimiento clínico esencial y elaborar, con un alto nivel de consenso, las recomendaciones necesarias para el manejo de la micosis invasiva en pacientes no neutropénicos. Métodos. Treinta expertos multidisciplinarios españoles en micosis invasiva (intensivistas, anestesistas, microbiólogos, farmacólogos y especialistas en enfermedades infecciosas) pertenecientes a 6 sociedades científicas contestaron anónimamente un cuestionario que evaluaba el grado de consenso mediante la técnica Delphi. Los expertos respondieron a 5 preguntas elaboradas por los coordinadores después de una revisión exhaustiva de la bibligorafía reciente. El grado de acuerdo necesario para seleccionar una categoría fue igual o superior al 70%. Posteriormente, 73 especialistas asistieron a una reunión en que se extrajeron las recomendaciones que se utilizaron en la elaboración de un algoritmo para la ayuda en la toma de una decisión clínica. Resultados. Las recomendaciones validadas e incluidas en el algoritmo fueron las siguientes: 1) varias situaciones se definieron como factores de riesgo para la candidiasis invasiva (CI) en pacientes no hematológicos; 2) no hubo acuerdo sobre el uso del índice de colonización para decidir la prescripción de tratamiento antifúngico precoz en pacientes estables (sin shock) con septicemia, sin foco evidente y con factores de riesgo para CI; 3) hubo acuerdo en el uso del Candida Score para decidir la prescripción de tratamiento antifúngico precoz en pacientes estables (sin shock) con septicemia, sin foco evidente y con factores de riesgo para CI; 4) hubo acuerdo en el inicio de tratamiento antifúngico precoz en pacientes estables (sin shock) con sepsis, sin foco evidente e índice de colonización >0,4 y con factores de riesgo para CI; 5) hubo acuerdo para realizar los procedimientos diagnósticos adicionales en pacientes estables (sin shock) con septicemia, sin foco evidente, factores de riesgo para CI e índice de colonización <0,4, pero con alto índice de sospecha. Conclusiones. Se ha elaborado un algoritmo de manejo de la CI en pacientes no neutropénicos basado en las recomendaciones de expertos. Este algoritmo puede ser útil como soporte a la prescripción a pie de cama (AU)

EPICO 3.0. Management of non-neutropenic patients in medical wards.

BACKGROUND: Although the management of invasive fungal infection (IFI) has improved, a number of controversies persist regarding the approach to invasive fungal infection in non-neutropenic medical ward patients. AIMS: To identify the essential clinical knowledge to elaborate a set of recommendations with a high level of consensus necessary for the management of IFI in non-neutropenic medical ward patients. METHODS: A prospective, Spanish questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all specialists (intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases) in IFI and belonging to six scientific national societies. They responded to five questions prepared by the coordination group after a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each category had to be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting held after extracting the recommendations from the chosen topics, and validated the pre-selected recommendations and derived algorithm. RESULTS: The following recommendations were validated and included in the algorithm: 1. several elements were identified as risk factors for invasive candidiasis (IC) in non-hematologic medical patients; 2. no agreement on the use of the colonization index to decide whether prescribing an early antifungal treatment to stable patients (no shock), with sepsis and no other evident focus and IC risk factors; 3. agreement on the use of the Candida Score to decide whether prescribing early antifungal treatment to stable patients (no shock) with sepsis and no other evident focus and IC risk factors; 4. agreement on initiating early antifungal treatment in stable patients (no shock) with a colonization index>0.4, sepsis with no other evident focus and IC risk factors; 5. agreement on the performance of additional procedures in stable patients (no shock) with sepsis and no other evident focus, IC risk factors, without colonization index>0.4, but with a high degree of suspicion. CONCLUSIONS: Based on the expert's recommendations, an algorithm for the management of non-neutropenic medical patients was constructed and validated. This algorithm may be useful to support bedside prescription.