Baricitinib or imatinib in hospitalized COVID-19 patients: Results from COVINIB, an exploratory randomized clinical trial.

Baricitinib and imatinib are considered therapies for coronavirus disease 2019 (COVID-19), but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients. Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day-by-day basis to identify differences ≥15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered, all-cause mortality, and safety. One hundred and sixty-five patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend toward better results in patients receiving baricitinib was found compared to standard care alone (hazard ratio [HR] for clinical improvement: 1.41, 95% confidence intervals [CI]: 0.96-2.06; HR for discontinuing oxygen: 1.46, 95% CI: 0.94-2.28). No differences were found regarding additional therapies administered or safety. Baricitinib plus standard care showed better results for hospitalized COVID-19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial.

Evaluation in a Cytokine Storm Model In Vivo of the Safety and Efficacy of Intravenous Administration of PRS CK STORM (Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells).

Our research group has been developing a series of biological drugs produced by coculture techniques with M2-polarized macrophages with different primary tissue cells and/or mesenchymal stromal cells (MSC), generally from fat, to produce anti-inflammatory and anti-fibrotic effects, avoiding the overexpression of pro-inflammatory cytokines by the innate immune system at a given time. One of these products is the drug PRS CK STORM, a medium conditioned by allogenic M2-polarized macrophages, from coculture, with those macrophages M2 with MSC from fat, whose composition, in vitro safety, and efficacy we studied. In the present work, we publish the results obtained in terms of safety (pharmacodynamics and pharmacokinetics) and efficacy of the intravenous application of this biological drug in a murine model of cytokine storm associated with severe infectious processes, including those associated with COVID-19. The results demonstrate the safety and high efficacy of PRS CK STORM as an intravenous drug to prevent and treat the cytokine storm associated with infectious processes, including COVID-19.

Cytokine Profile and Anti-Inflammatory Activity of a Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells (PRS CK STORM).

Intercellular communication between monocytes/macrophages and cells involved in tissue regeneration, such as mesenchymal stromal cells (MSCs) and primary tissue cells, is essential for tissue regeneration and recovery of homeostasis. Typically, in the final phase of the inflammation-resolving process, this intercellular communication drives an anti-inflammatory immunomodulatory response. To obtain a safe and effective treatment to counteract the cytokine storm associated with a disproportionate immune response to severe infections, including that associated with COVID-19, by means of naturally balanced immunomodulation, our group has standardized the production under GMP-like conditions of a secretome by coculture of macrophages and MSCs. To characterize this proteome, we determined the expression of molecules related to cellular immune response and tissue regeneration, as well as its possible toxicity and anti-inflammatory potency. The results show a specific molecular pattern of interaction between the two cell types studied, with an anti-inflammatory and regenerative profile. In addition, the secretome is not toxic by itself on human PBMC or on THP-1 monocytes and prevents lipopolysaccharide (LPS)-induced growth effects on those cell types. Finally, PRS CK STORM prevents LPS-induced TNF-A and IL-1Β secretion from PBMC and from THP-1 cells at the same level as hydrocortisone, demonstrating its anti-inflammatory potency.

Hospital Pharmacist experience in the Intensive Care Unit: Plan COVID.

The Intensive Care Unit (ICU) of the University Hospital of Fuenlabrada was  forced to critically increase its capacity in the COVID-19 pandemic. The objective of this work is to describe the activities promoted by the pharmacist in the care  of the critically ill patient in this context. A new organizational structure was  designed, analyzing the tasks necessary to make the processes profitable. Two  pharmacists joined the critical patient care to help the pharmacist who was  already integrated in the ICU team. The development of the operational  structure was carried out on three levels. The healthcare activity highlights the  daily participation of pharmacists in the two clinical sessions in which the ICU  teams evaluated all cases and made decisions. This in turn facilitated the  pharmaceutical validation that was carried out in the critical units themselves. In addition, one of the pharmacists created the Immuno-COVID Committee, in  which they participated together with different specialists for therapeutic  decision-making in the most complex cases. On the other hand, the availability  of human and material resources allowed the implantation of centralized  elaboration in the Pharmacy Service of many intravenous mixtures, including  antibiotics elastomers Pumps for continuous infusion, and non-sterile  elaborations. In logistics management, in addition to the acquisition of COVID- 19 therapies, the reconciliation with nursing activity stands out. The physical presence of the pharmacist favored the detection of needs, the  availability in time of medications in the unit, including sterile and non-sterile  preparations, and coordination with the central pharmacy. In knowledge  management, the participation of the pharmacist in the working group for the  development of the hospital management protocol COVID-19 stands out. The  daily presence in the unit and the joint work with the entire multidisciplinary team demonstrate the value that the pharmacist can bring. In addition to  efficient resource management, support for clinical decision-making and  improvement actions, it provides the climate of inter-professional trust necessary to respond to the complexity of the critical patient and promote joint  projects.

La Unidad de Cuidados Intensivos del Hospital Universitario de Fuenlabrada se  vio obligada a aumentar de manera crítica su capacidad en la pandemia por  COVID-19. El objetivo de este trabajo es describir las actividades impulsadas por el farmacéutico en la atención del paciente crítico en este contexto. Se diseñó  una estructura organizativa nueva, analizando las tareas necesarias para  rentabilizar los procesos. Dos farmacéuticos se incorporaron a la atención del  paciente crítico para ayudar al farmacéutico que ya estaba integrado en el  equipo de la Unidad de Cuidados Intensivos. El desarrollo de la estructura  operativa se llevó a cabo en tres niveles. En la actividad asistencial destaca la  participación diaria de los farmacéuticos en las dos sesiones clínicas en las que  los equipos de la Unidad de Cuidados Intensivos valoraban todos los casos y  tomaban las decisiones. Esto, a su vez, facilitaba la validación farmacéutica que  se realizaba en las propias unidades de críticos. Además, uno de los  farmacéuticos ideó el Comité Inmuno-COVID, en el que participaban junto a  diferentes especialistas para la toma de decisiones terapéuticas en los casos más complejos. Por otro lado, la disponibilidad de recursos humanos y materiales  permitió implantar la elaboración de forma centralizada en el Servicio de Farmacia de muchas mezclas intravenosas, incluyendo elastómeros de  antibioterapia en perfusión continua, y de elaboraciones no estériles. En la  gestión logística, además de la adquisición de las terapias COVID-19, destaca la  conciliación con la actividad de enfermería. La presencia física del farmacéutico  favorecía la detección de necesidades, la disponibilidad en tiempo de  medicamentos en la unidad, incluyendo las elaboraciones estériles y no estériles, y la coordinación con la Farmacia central. En la gestión del conocimiento destaca la participación del farmacéutico en el grupo de trabajo para desarrollo del  protocolo hospitalario de manejo de la COVID-19. La presencia diaria en la  unidad y el trabajo conjunto con todo el equipo multidisciplinar ponen de  manifiesto el valor que el farmacéutico puede aportar. Además de una gestión  eficiente de los recursos, soporte en la toma de decisiones clínicas y acciones de  mejora, proporciona el clima de confianza interprofesional necesario para dar  respuesta a la complejidad del paciente crítico y promover proyectos conjuntos.

Experiencia del farmacéutico de hospital en la unidad de cuidados intensivos: Plan COVID / Hospital Pharmacist experience in the Intensive Care Unit: Plan COVID

La Unidad de Cuidados Intensivos del Hospital Universitario de Fuenlabrada se vio obligada a aumentar de manera crítica su capacidad en la pandemia por COVID-19. El objetivo de este trabajo es describir las actividades impulsadas por el farmacéutico en la atención del paciente crítico en este contexto. Se diseñó una estructura organizativa nueva, analizando las tareas necesarias para rentabilizar los procesos. Dos farmacéuticos se incorporaron a la atención del paciente crítico para ayudar al farmacéutico que ya estaba integrado en el equipo de la Unidad de Cuidados Intensivos. El desarrollo de la estructura operativa se llevó a cabo en tres niveles. En la actividad asistencial destaca la participación diaria de los farmacéuticos en las dos sesiones clínicas en las que los equipos de la Unidad de Cuidados Intensivos valoraban todos los casos y tomaban las decisiones. Esto, a su vez, facilitaba la validación farmacéutica que se realizaba en las propias unidades de críticos. Además, uno de los farmacéuticos ideó el Comité Inmuno-COVID, en el que participaban junto a diferentes especialistas para la toma de decisiones terapéuticas en los casos más complejos. Por otro lado, la disponibilidad de recursos humanos y materiales permitió implantar la elaboración de forma centralizada en el Servicio de Farmacia de muchas mezclas intravenosas, incluyendo elastómeros de antibioterapia en perfusión continua, y de elaboraciones no estériles. En la gestión logística, además de la adquisición de las terapias COVID-19, destaca la conciliación con la actividad de enfermería. La presencia física del farmacéutico favorecía la detección de necesidades, la disponibilidad en tiempo de medicamentos en la unidad, incluyendo las elaboraciones estériles y no estériles, y la coordinación con la Farmacia central. En la gestión del conocimiento destaca la participación del farmacéutico en el grupo de trabajo para desarrollo del protocolo hospitalario de manejo de la COVID-19. La presencia diaria en la unidad y el trabajo conjunto con todo el equipo multidisciplinar ponen de manifiesto el valor que el farmacéutico puede aportar. Además de una gestión eficiente de los recursos, soporte en la toma de decisiones clínicas y acciones de mejora, proporciona el clima de confianza interprofesional necesario para dar respuesta a la complejidad del paciente crítico y promover proyectos conjuntos

The Intensive Care Unit (ICU) of the University Hospital of Fuenlabrada was forced to critically increase its capacity in the COVID-19 pandemic. The objective of this work is to describe the activities promoted by the pharmacist in the care of the critically ill patient in this context. A new organizational structure was designed, analyzing the tasks necessary to make the processes profitable. Two pharmacists joined the critical patient care to help the pharmacist who was already integrated in the ICU team. The development of the operational structure was carried out on three levels. The healthcare activity highlights the daily participation of pharmacists in the two clinical sessions in which the ICU teams evaluated all cases and made decisions. This in turn facilitated the pharmaceutical validation that was carried out in the critical units themselves. In addition, one of the pharmacists created the Immuno-COVID Committee, in which they participated together with different specialists for therapeutic decision-making in the most complex cases. On the other hand, the availability of human and material resources allowed the implantation of centralized elaboration in the Pharmacy Service of many intravenous mixtures, including antibiotics elastomers Pumps for continuous infusion, and non-sterile elaborations. In logistics management, in addition to the acquisition of COVID-19 therapies, the reconciliation with nursing activity stands out. The physical presence of the pharmacist favored the detection of needs, the availability in time of medications in the unit, including sterile and non-sterile preparations, and coordination with the central pharmacy. In knowledge management, the participation of the pharmacist in the working group for the development of the hospital management protocol COVID-19 stands out. The daily presence in the unit and the joint work with the entire multidisciplinary team demonstrate the value that the pharmacist can bring. In addition to efficient resource management, support for clinical decision-making and improvement actions, it provides the climate of inter-professional trust necessary to respond to the complexity of the critical patient and promote joint projects