Synthesis of bis-furyl-pyrrolo[3,4-b]pyridin-5-ones via Ugi-Zhu reaction and in vitro activity assays against human SARS-CoV-2 and in silico studies on its main proteins.

An Ugi-Zhu three-component reaction (UZ-3CR) coupled in one pot manner to a cascade process (N-acylation/aza Diels-Alder cycloaddition/decarboxylation/dehydration) was performed to synthesize a series of bis-furyl-pyrrolo[3,4-b]pyridin-5-ones in 45 to 82% overall yields using ytterbium triflate as a catalyst, toluene as a solvent, and microwaves as a heat source. The synthesized molecules were evaluated in vitro against human SARS-CoV-2 through a time-of-addition approach, finding that compound 1e, at a concentration of 10.0 µM, exhibited a significant reduction at the initial infection stages, thus showing prophylactic potential. On the other hand, it was found that compound 1d, at the same concentration, was significantly active when applied post-infection, thus exhibiting a therapeutic profile. Moreover, compound 1f showed both, prophylactic and therapeutic activity. Then, to understand interactions between synthesized compounds and the main proteins related to the virus, docking studies were performed on spike-glycoprotein, main-protease, and Nsp3 protein, finding moderate to strong binding energies, matching accurately with the in vitro results. Additionally, a pharmacophore model was computed behind further rational drug design.

Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos / 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 (AU)

La pandemia por COVID-19 ha provocado el ingreso de un elevado número de pacientes en UCI, generalmente por insuficiencia respiratoria severa. Desde la aparición de los primeros casos de infección por SARS-CoV-2, a finales de 2019, en China, se ha publicado una cantidad ingente de recomendaciones de tratamiento de esta entidad, no siempre respaldadas por evidencia científica suficiente ni con el rigor metodológico necesario. Gracias al esfuerzo de distintos grupos de investigadores, actualmente disponemos de resultados de ensayos clínicos, y otro tipo de estudios, de mayor calidad. Consideramos necesario realizar un documento que incluya recomendaciones que recojan estas evidencias en cuanto al diagnóstico y el tratamiento de COVID-19, pero también aspectos que otras guías no han contemplado y que consideramos fundamentales en el manejo del paciente crítico con COVID-19. Para ello se ha creado un comité redactor, conformado por miembros de los Grupos de Trabajo de SEMICYUC más directamente relacionados con diferentes aspectos específicos del manejo de estos pacientes (AU)

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.

[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.

[Relevance of empirical antibiotic treatment in the evolution of prosthetic joint infection treated with implant retention]. / Relevancia del tratamiento antibiótico empírico en la evolución de la infección de prótesis articular tratada con retención del implante.

OBJECTIVE: Several factors have been associated with the prognosis of prosthetic joint infection (PJI) treated with surgical debridement, antibiotic therapy, and implant retention (DAIR). There is no evidence about the right empirical antibiotic treatment when the causal microorganism is not still identified. METHODS: We conducted a retrospective observational study in patients with PJI treated with DAIR between 2009 and 2018 in our center. We analyze the risk factors related with their prognosis and the influence of active empirical antibiotic therapy against causative microorganisms in final outcomes. RESULTS: A total of 80 PJI cases treated with DAIR, from 79 patients (58.7% women, mean age 76.3 years), were included in the study period. Among the cases in which empirical antibiotic therapy were active against the causative microorganisms, the success rate was 46/65 (69.2%) vs 1/15 when not (6.7%, OR 31.5, p = 0.001). Factors related to the success or failure of the DAIR were analyzed with multivariate analysis. We found that active empirical antibiotic treatment remained statistically significant as a good prognostic factor (OR 0.04, p <0.01). CONCLUSIONS: Empirical antibiotic treatment could be an important factor in the prognosis of PJI treated with DAIR. To identify cases at risk of infection by multidrug resistant microorganisms could be useful to guide empirical antibiotic therapy.

[Recommendations of the Working Groups from the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) for the management of adult critically ill patients in the coronavirus disease (COVID-19)]. / Recomendaciones de «hacer¼ y «no hacer¼ en el tratamiento de los pacientes críticos ante la pandemia por coronavirus causante de COVID-19 de los Grupos de Trabajo de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC).

On March 11, 2020, the Director-General of the World Health Organization (WHO) declared the disease caused by SARS-CoV-2 (COVID-19) as a pandemic. The spread and evolution of the pandemic is overwhelming the healthcare systems of dozens of countries and has led to a myriad of opinion papers, contingency plans, case series and emerging trials. Covering all this literature is complex. Briefly and synthetically, in line with the previous recommendations of the Working Groups, the Spanish Society of Intensive, Critical Medicine and Coronary Units (SEMICYUC) has prepared this series of basic recommendations for patient care in the context of the pandemic.

Sobresedación Zero como herramienta de confort, seguridad y gestión en la unidades de cuidados intensivos / Oversedation Zero as a tool for comfort, safety and intensive care unit management

La sedación es necesaria en el tratamiento de los pacientes críticos, tanto para aliviar el sufrimiento como para curar a los pacientes con enfermedades que precisan el ingreso en unidades de cuidados intensivos. Esta sedación debe ser la adecuada a las necesidades del paciente en cada momento de su evolución clínica, ni por debajo (infrasedación) ni por encima (sobresedación). Una sedación adecuada influye en la comodidad, la seguridad, la supervivencia, la calidad de vida posterior, la rotación de camas de las unidades de críticos y los costes. La infrasedación se detecta y corrige rápidamente. Sin embargo, la sobresedación es silente y difícil de prevenir sin unas pautas de actuación, una concienciación colectiva y un trabajo en equipo. El proyecto «Sobresedación Zero» del Grupo de Trabajo de Sedación, Analgesia y Delirium de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias pretende ser una herramienta docente, práctica y de concienciación colectiva de comodidad, seguridad y gestión para maximizar el resultado clínico y minimizar los efectos perjudiciales de la sedación excesiva. Se basa en un paquete de medidas que se incluye monitorizar el dolor, la analgesia, la agitación, la sedación, el delirium y el bloqueo neuromuscular, mantener a los pacientes sin dolor, realizar una sedación dinámica según objetivos clínicos, consensuar el protocolo multidisciplinar a seguir y evitar la sedación profunda no indicada clínicamente

Sedation is necessary in the management of critically ill patients, both to alleviate suffering and to cure patients with diseases that require admission to the intensive care unit. Such sedation should be appropriate to the patient needs at each timepoint during clinical evolution, and neither too low (undersedation) nor too high (oversedation). Adequate sedation influences patient comfort, safety, survival, subsequent quality of life, bed rotation of critical care units and costs. Undersedation is detected and quickly corrected. In contrast, oversedation is silent and difficult to prevent in the absence of management guidelines, collective awareness and teamwork. The Zero Oversedation Project of the Sedation, Analgesia and Delirium Working Group of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units aims to offer a practical teaching and collective awareness tool for ensuring patient comfort, safety and management with a view to optimizing the clinical outcomes and minimizing the deleterious effects of excessive sedation. The tool is based on a package of measures that include monitoring pain, analgesia, agitation, sedation, delirium and neuromuscular block, keeping patients pain-free, performing dynamic sedation according to clinical objectives, agreeing upon the multidisciplinary protocol to be followed, and avoiding deep sedation where not clinically indicated

Oversedation Zero as a tool for comfort, safety and intensive care unit management. / Sobresedación Zero como herramienta de confort, seguridad y gestión en la unidades de cuidados intensivos.

Sedation is necessary in the management of critically ill patients, both to alleviate suffering and to cure patients with diseases that require admission to the intensive care unit. Such sedation should be appropriate to the patient needs at each timepoint during clinical evolution, and neither too low (undersedation) nor too high (oversedation). Adequate sedation influences patient comfort, safety, survival, subsequent quality of life, bed rotation of critical care units and costs. Undersedation is detected and quickly corrected. In contrast, oversedation is silent and difficult to prevent in the absence of management guidelines, collective awareness and teamwork. The Zero Oversedation Project of the Sedation, Analgesia and Delirium Working Group of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units aims to offer a practical teaching and collective awareness tool for ensuring patient comfort, safety and management with a view to optimizing the clinical outcomes and minimizing the deleterious effects of excessive sedation. The tool is based on a package of measures that include monitoring pain, analgesia, agitation, sedation, delirium and neuromuscular block, keeping patients pain-free, performing dynamic sedation according to clinical objectives, agreeing upon the multidisciplinary protocol to be followed, and avoiding deep sedation where not clinically indicated.