Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine.

Sepsis is characterised by a dysregulated host immune response to infection. Despite recognition of its significance, immune status monitoring is not implemented in clinical practice due in part to the current absence of direct therapeutic implications. Technological advances in immunological profiling could enhance our understanding of immune dysregulation and facilitate integration into clinical practice. In this Review, we provide an overview of the current state of immune profiling in sepsis, including its use, current challenges, and opportunities for progress. We highlight the important role of immunological biomarkers in facilitating predictive enrichment in current and future treatment scenarios. We propose that multiple immune and non-immune-related parameters, including clinical and microbiological data, be integrated into diagnostic and predictive combitypes, with the aid of machine learning and artificial intelligence techniques. These combitypes could form the basis of workable algorithms to guide clinical decisions that make precision medicine in sepsis a reality and improve patient outcomes.

High-flow nasal cannula and non-invasive mechanical ventilation in pediatric asthma exacerbation: two-year prospective observational study in intensive care / Cánula nasal de alto flujo y ventilación no invasiva en asma pediátrico grave: estudio observacional prospectivo de dos años de duración en cuidados intensivos

Abstract Background: Asthma is a common cause of admission to the pediatric intensive care unit (PICU). We described and analyzed the therapies applied to children admitted to a tertiary PICU because of asthma. Later, we evaluated high-flow nasal cannula (HFNC) use in these patients and compared their evolution and complications with those who received non-invasive ventilation. Methods: We conducted a prospective observational study (October 2017-October 2019). Collected data: epidemiological, clinical, respiratory support therapy needed, complementary tests, and PICU and hospital stay. Patients were divided into three groups: (1) only HFNC; (2) HFNC and non-invasive mechanical ventilation (NIMV); and (3) only NIMV. Results: Seventy-six patients were included (39 female). The median age was 2 years and 1 month. The median pulmonary score was 5. The median PICU stay was 3 days, and the hospital stay was 6 days. Children with HNFC only (56/76) had fewer PICU days (p = 0.025) and did not require NIMV (6/76). Children with HFNC had a higher oxygen saturation/fraction of inspired oxygen ratio ratio (p = 0.025) and lower PCO2 (p = 0.032). In the group receiving both therapies (14/76), NIMV was used first in all cases. No epidemiologic or clinical differences were found among groups. Conclusion: HFNC was a safe approach that did not increase the number of PICU or hospital days. On admission, normal initial blood gases and the absence of high oxygen requirements were useful in selecting responders to HFNC. Further randomized and multicenter clinical trials are needed to verify these data.

Resumen Introducción: El asma es una causa frecuente de ingreso en la unidad de cuidados intensivos pediátricos (UCIP). En este, cuadro el uso de cánula nasal de alto flujo (CNAF) se ha visto extendido. En este trabajo se describe el tratamiento global en la UCIP ante el ingreso por asma en un hospital monográfico pediátrico y se evalúa la respuesta al uso de la CNAF, comparando la evolución de los pacientes con aquellos que recibieron ventilación no invasiva (VNI). Métodos: Se llevó a cabo un estudio observacional prospectivo (de octubre del 2017 a octubre del 2019). Se describieron epidemiología, clínica, tratamiento y soporte respiratorio. Para la comparación se crearon tres grupos de pacientes: 1) solo CNAF; 2) CNAF y VNI; y 3) solo VNI. Resultados: Se incluyeron 76 pacientes. La mediana de edad fue de dos años y un mes; la mediana de índice pulmonar fue 5. La mediana de ingreso en UCIP fue de tres días y de ingreso hospitalario, seis días. Los niños con solo CNAF (56/76) mostraron menos días de UCIP (p = 0.025) y no requirieron VNI (6/76). También mostraron mayor SatO2/FiO2 (saturación de oxígeno/fracción de oxígeno inspirado) (p = 0.025) y menor nivel de PCO2 (presión parcial de CO2) (p = 0.032). La VNI se utilizó primero siempre en el grupo que recibió ambas modalidades (14/76). No se encontraron diferencias epidemiológicas o clínicas entre grupos. Conclusiones: En nuestra serie, el uso de CNAF no aumentó los días de ingreso en la UCIP ni de hospital. Tampoco requirió cambio a VNI. Al ingreso, una gasometría normal y bajo requerimiento de oxígeno permitieron seleccionar a los pacientes respondedores. Se necesitan más ensayos multicéntricos clínicos aleatorizados para verificar estos datos.

High-flow nasal cannula and non-invasive mechanical ventilation in pediatric asthma exacerbation: two-year prospective observational study in intensive care.

BACKGROUND: Asthma is a common cause of admission to the pediatric intensive care unit (PICU). We described and analyzed the therapies applied to children admitted to a tertiary PICU because of asthma. Later, we evaluated high-flow nasal cannula (HFNC) use in these patients and compared their evolution and complications with those who received non-invasive ventilation. METHODS: We conducted a prospective observational study (October 2017-October 2019). Collected data: epidemiological, clinical, respiratory support therapy needed, complementary tests, and PICU and hospital stay. Patients were divided into three groups: (1) only HFNC; (2) HFNC and non-invasive mechanical ventilation (NIMV); and (3) only NIMV. RESULTS: Seventy-six patients were included (39 female). The median age was 2 years and 1 month. The median pulmonary score was 5. The median PICU stay was 3 days, and the hospital stay was 6 days. Children with HNFC only (56/76) had fewer PICU days (p = 0.025) and did not require NIMV (6/76). Children with HFNC had a higher oxygen saturation/fraction of inspired oxygen ratio ratio (p = 0.025) and lower PCO2 (p = 0.032). In the group receiving both therapies (14/76), NIMV was used first in all cases. No epidemiologic or clinical differences were found among groups. CONCLUSION: HFNC was a safe approach that did not increase the number of PICU or hospital days. On admission, normal initial blood gases and the absence of high oxygen requirements were useful in selecting responders to HFNC. Further randomized and multicenter clinical trials are needed to verify these data.

INTRODUCCIÓN: El asma es una causa frecuente de ingreso en la unidad de cuidados intensivos pediátricos (UCIP). En este, cuadro el uso de cánula nasal de alto flujo (CNAF) se ha visto extendido. En este trabajo se describe el tratamiento global en la UCIP ante el ingreso por asma en un hospital monográfico pediátrico y se evalúa la respuesta al uso de la CNAF, comparando la evolución de los pacientes con aquellos que recibieron ventilación no invasiva (VNI). MÉTODOS: Se llevó a cabo un estudio observacional prospectivo (de octubre del 2017 a octubre del 2019). Se describieron epidemiología, clínica, tratamiento y soporte respiratorio. Para la comparación se crearon tres grupos de pacientes: 1) solo CNAF; 2) CNAF y VNI; y 3) solo VNI. RESULTADOS: Se incluyeron 76 pacientes. La mediana de edad fue de dos años y un mes; la mediana de índice pulmonar fue 5. La mediana de ingreso en UCIP fue de tres días y de ingreso hospitalario, seis días. Los niños con solo CNAF (56/76) mostraron menos días de UCIP (p = 0.025) y no requirieron VNI (6/76). También mostraron mayor SatO2/FiO2 (saturación de oxígeno/fracción de oxígeno inspirado) (p = 0.025) y menor nivel de PCO2 (presión parcial de CO2) (p = 0.032). La VNI se utilizó primero siempre en el grupo que recibió ambas modalidades (14/76). No se encontraron diferencias epidemiológicas o clínicas entre grupos. CONCLUSIONES: En nuestra serie, el uso de CNAF no aumentó los días de ingreso en la UCIP ni de hospital. Tampoco requirió cambio a VNI. Al ingreso, una gasometría normal y bajo requerimiento de oxígeno permitieron seleccionar a los pacientes respondedores. Se necesitan más ensayos multicéntricos clínicos aleatorizados para verificar estos datos.

Characteristics and management of patients with SARS-CoV2 infection admitted to pediatric intensive care units: Data analysis of the Spanish national multicenter registry.

INTRODUCTION: The purpose of this study is to describe the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) disease characteristics and management in children admitted to the pediatric intensive care units (PICU). METHODS: The present study was based on a national multicentric prospective registry including PICU patients with SARS-CoV2 infection or symptoms of multisystem inflammatory syndrome in children (MIS-C). RESULTS: A total of 298 patients were admitted to 41 different Spanish PICUs. A total of 76% of them were previously healthy. The most frequent manifestation was MIS-C (69.8%). On admission, 59.4% of patients did not have respiratory distress, and only 17.4% needed conventional mechanical ventilation (MV). The need for MV was associated with age (incidence rate ratios [IRR] 1.21, p < .012), pediatric sequential organ failure assessment score (p-SOFA) Score (IRR 1.12, p = .001), and need for transfusion (IRR 4.5, p < .004) in MIS-C patients, and with vasoactive drug use (IRR 2.73, p = .022) and the diagnosis of acute respiratory distress syndrome (IRR 2.83, p = .018) in patients admitted for other reasons. During the first day of admission, 56% of patients met shock criteria and 50.7% needed vasoactive drugs. In MIS-C patients, their use was associated with higher p-SOFA score (IRR 1.06, p < .001) and with the diagnosis of shock (IRR 5.78, p < .001). In patients without MIS-C, it was associated with higher p-SOFA score (IRR 1.05, p = .022). The mortality rate was 3%, being lower in MIS-C patients compared to patients admitted for other reasons (0.5% vs. 9.4%, p < .001). It was also lower in previously healthy patients compared to patients with previous comorbidities (0.9% vs. 9.7%, p < .001). CONCLUSIONS: Severe SARS-CoV2 infection is uncommon in the pediatric population. In our series, respiratory distress was rare, being MIS-C the most frequent cause of PICU admission related to SARS-CoV2. In most cases, the course of the disease was mild except in children with previous diseases.

IgG antispike persistence and immunophenotype in children infected by SARS-CoV-2.

AIM: The immune status of children recovering from SARS-CoV-2 infection is not completely understood. We describe IgG antispike persistence in children infected during the first two pandemic waves. In addition, we compared with healthy controls their leukocyte populations and CD64 expression. METHODS: Cross-sectional study. Carried out from October 2021 to February 2022 in nonreinfected and nonvaccinated children with SARS-CoV-2 in 2020. The presence of antispike IgG was studied using chemiluminescent immunoassay. Leukocyte populations were analysed using flow cytometry and marked for CD45, CD4, CD8 and CD64. Statistical minor than 0.05 was considered significant. RESULTS: One hundred and eighty-three control and 77 patients were included. IgG antispike determinations were performed after a median of 501 days (262-464); 52 of 77 children were positive. Cases showed significantly higher percentages of monocytes, lymphocytes, CD8+ and CD4+ . In addition, CD64 expression was higher in monocytes and neutrophils. The presence of IgG antispike was accompanied by a higher percentage of CD64+ neutrophils. CONCLUSION: In our series, the SARS-CoV-2 IgG antispike protein was usually positive beyond 1 year after infection. Furthermore, leukocyte populations from cases differ from controls, with higher CD64 expression on neutrophils and monocytes. Prospective clinical observations are required to confirm the implications of these findings.

Fatal Pulmonary Veno-Occlusive Disease and Systemic Juvenile Idiopathic Arthritis: Case Report and Literature Review.

Systemic juvenile idiopathic arthritis (sJIA) is a chronic childhood inflammatory disease. SJIA accounts for approximately 5-15 per cent of all cases of JIA and has a high morbidity and mortality rate. In this disease, pulmonary complications (PC) other than pleuritis are much less frequent and not easily recognised by clinicians. Pulmonary hypertension, the most severe PC, is associated with uncontrolled disease and use of biologic therapies. We present a case of a school-age female with sJIA who died of acute cardiopulmonary instability secondary to pulmonary venous-occlusive disease demonstrated by necropsy. We describe her clinical evolution. We also undertook a narrative review of the literature about PC in sJIA to discuss the current state of the art regarding this complication. High disease activity and the use of multiple therapies include disease-modifying anti-rheumatic drugs should be a red flag for clinicians when discounting PC and pulmonary hypertension. The combination of chest X-ray, electrocardiogram and echocardiogram appear to be the best tests to achieve an early diagnosis.

Fatal Pulmonary Veno-Occlusive Disease and Systemic Juvenile Idiopathic Arthritis: Case Report and Literature Review / Enfermedad venooclusiva fatal y artritis idiopática juvenil sistémica: caso clínico y revisión de la literatura

Systemic juvenile idiopathic arthritis (sJIA) is a chronic childhood inflammatory disease. SJIA accounts for approximately 5–15 per cent of all cases of JIA and has a high morbidity and mortality rate. In this disease, pulmonary complications (PC) other than pleuritis are much less frequent and not easily recognised by clinicians. Pulmonary hypertension, the most severe PC, is associated with uncontrolled disease and use of biologic therapies. We present a case of a school-age female with sJIA who died of acute cardiopulmonary instability secondary to pulmonary venous-occlusive disease demonstrated by necropsy. We describe her clinical evolution. We also undertook a narrative review of the literature about PC in sJIA to discuss the current state of the art regarding this complication. High disease activity and the use of multiple therapies include disease-modifying anti-rheumatic drugs should be a red flag for clinicians when discounting PC and pulmonary hypertension. The combination of chest X-ray, electrocardiogram and echocardiogram appear to be the best tests to achieve an early diagnosis.(AU)

La artritis idiopática juvenil sistémica (AIJs) es una enfermedad juvenil crónica que representa aproximadamente del 5 al 15% de todos los casos de AIJ y tiene una elevada tasa de morbimortalidad. En esta enfermedad, las complicaciones pulmonares (CP) distintas a pleuritis son mucho menos frecuentes, y no fácilmente reconocibles por los clínicos. La hipertensión pulmonar, la CP más grave, está asociada a la enfermedad incontrolada y el uso de terapias biológicas. Presentamos el caso de una mujer en edad escolar con AIJs que falleció debido a inestabilidad cardiopulmonar aguda secundaria a enfermedad venosooclusiva confirmada en la necropsia. Describimos su evolución clínica, y también realizamos una revisión narrativa de la literatura relativa a CP en AIJs, para debatir los avances más recientes sobre esta complicación. La elevada actividad de la enfermedad y el uso de terapias múltiples que incluyen fármacos antirreumáticos modificadores de la enfermedad deberían servir de signo de alarma a los clínicos para descartar CP e hipertensión pulmonar. La combinación de placas de tórax, electrocardiograma y ecocardiograma parece ser el mejor conjunto de pruebas para lograr un diagnóstico precoz.(AU)

Actualización del enfoque paliativo en la Unidad de Cuidados Intensivos Pediátricos / Update on the palliative care approach at the pediatric intensive care unit

Los cuidados paliativos pediátricos pretenden mejorar la atención y la calidad de vida de los niños en situación terminal o con una enfermedad de pronóstico letal. En el contexto hospitalario, las decisiones y tratamientos vinculados al final de la vida se realizan de forma frecuente en las unidades de cuidados intensivos. Es por esto que la integración de los cuidados paliativos en estos servicios constituye una evolución lógica del abordaje clínico del niño grave. Se realiza en este trabajo una actualización acerca de las indicaciones y particularidades del enfoque paliativo en el contexto de los cuidados intensivos pediátricos. Se contemplan el inicio del enfoque paliativo, la toma de decisiones, los aspectos comunicativos, el tratamiento farmacológico, el manejo de síntomas y la sedación paliativa.

Pediatric palliative care aims at improving the care and quality of life of children who are terminally ill or have a fatal prognosis. In the hospital setting, end-of-life decisions and treatments are common in intensive care units. This is why the integration of palliative care in these units is a logical evolution of the clinical approach to severely ill children. This study provides an update on the indications and characteristics of the palliative care approach in the context of pediatric intensive care. Here we describe palliative care approach initiation, decision-making, communicative aspects, drug treatment, symptom management, and palliative sedation.

Update on the palliative care approach at the pediatric intensive care unit. / Actualización del enfoque paliativo en la Unidad de Cuidados Intensivos Pediátricos.

Pediatric palliative care aims at improving the care and quality of life of children who are terminally ill or have a fatal prognosis. In the hospital setting, end-of-life decisions and treatments are common in intensive care units. This is why the integration of palliative care in these units is a logical evolution of the clinical approach to severely ill children. This study provides an update on the indications and characteristics of the palliative care approach in the context of pediatric intensive care. Here we describe palliative care approach initiation, decision-making, communicative aspects, drug treatment, symptom management, and palliative sedation.

Los cuidados paliativos pediátricos pretenden mejorar la atención y la calidad de vida de los niños en situación terminal o con una enfermedad de pronóstico letal. En el contexto hospitalario, las decisiones y tratamientos vinculados al final de la vida se realizan de forma frecuente en las unidades de cuidados intensivos. Es por esto que la integración de los cuidados paliativos en estos servicios constituye una evolución lógica del abordaje clínico del niño grave. Se realiza en este trabajo una actualización acerca de las indicaciones y particularidades del enfoque paliativo en el contexto de los cuidados intensivos pediátricos. Se contemplan el inicio del enfoque paliativo, la toma de decisiones, los aspectos comunicativos, el tratamiento farmacológico, el manejo de síntomas y la sedación paliativa.

Multisystem Inflammatory Syndrome in Children in Western Countries? Decreasing Incidence as the Pandemic Progresses?: An Observational Multicenter International Cross-sectional Study.

BACKGROUND: SARS-CoV-2 variations as well as immune protection after previous infections and/or vaccination may have altered the incidence of multisystemic inflammatory syndrome in children (MIS-C). We aimed to report an international time-series analysis of the incidence of MIS-C to determine if there was a shift in the regions or countries included into the study. METHODS: This is a multicenter, international, cross-sectional study. We collected the MIS-C incidence from the participant regions and countries for the period July 2020 to November 2021. We assessed the ratio between MIS-C cases and COVID-19 pediatric cases in children <18 years diagnosed 4 weeks earlier (average time for the temporal association observed in this disease) for the study period. We performed a binomial regression analysis for 8 participating sites [Bogotá (Colombia), Chile, Costa Rica, Lazio (Italy), Mexico DF, Panama, The Netherlands and Catalonia (Spain)]. RESULTS: We included 904 cases of MIS-C, among a reference population of 17,906,432 children. We estimated a global significant decrease trend ratio in MIS-C cases/COVID-19 diagnosed cases in the previous month ( P < 0.001). When analyzing separately each of the sites, Chile and The Netherlands maintained a significant decrease trend ( P < 0.001), but this ratio was not statistically significant for the rest of sites. CONCLUSIONS: To our knowledge, this is the first international study describing a global reduction in the trend of the MIS-C incidence during the pandemic. COVID-19 vaccination and other factors possibly linked to the virus itself and/or community transmission may have played a role in preventing new MIS-C cases.

PIMS-TS immunophenotype: description and comparison with healthy children, Kawasaki disease and severe viral and bacterial infections.

BACKGROUND: A new clinical syndrome named Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) has been described. This new disease is a leading cause of hospital and paediatric intensive care unit (PICU). It has been related to immunity dysregulation. METHODS: Prospective-retrospective observational study to describe the innate cell signature and immunophenotype of children admitted to PICU because of PIMS-TS (from March 2020 to September 2020). The immunophenotype was done through the expression analysis of these proteins of mononuclear cells: CD64, CD18, CD11a and CD11b. They were compared with previous healthy controls and children admitted to PICU because of bacterial infection, viral infection and Kawasaki disease (KD). Two hundred and forty-seven children were studied: 183 healthy controls, 25 viral infections, 20 bacterial infections, 6 KD and 13 PIMS-TS. RESULTS: PIMT-TS showed the lowest percentage of lymphocytes and monocytes with higher relative numbers of CD4+ (p = .000). Monocytes and neutrophils in PIMS-TS showed higher levels of CD64 expression (p = .000). Also, CD11a and CD11b were highly expressed (p =,000). CONCLUSION: We observed a differential cell innate signature in PIMS-TS. These findings are consistent with a proinflammatory status (CD64 elevated expression) and lymphocyte trafficking to tissues (CD11a and CD11b). More studies should be carried out to confirm our results.

Palliative home-based care to pediatric cancer patients: characteristics and healthcare delivered.

OBJECTIVES: Cancer patients constitute an important group in pediatric palliative care. Though the patients' home is the preferred place of care, little is known about the characteristics of patients attended by units that provide home assistance. Our objective is to describe the characteristics of cancer patients and healthcare delivered by a pediatric palliative care unit with a home hospitalization program. METHODS: Retrospective study based on clinical records of deceased patients attended by the pediatric palliative care unit of Madrid over 10 years. Data collected included general characteristics, type of cancer, whether they received home assistance, place of death, healthcare delivered (hospitalizations, devices, oncological treatments…), and symptom prevalence. RESULTS: After excluding 47 patients, the clinical records of 144 patients were analyzed. The median age at referral was 9.4 years (IQR: 5.6-14.1), 61.2% were males; 44.2% had solid non-CNS tumors, 35.4% CNS tumors, and 20.4% hematological malignancies; 137 received home care with 89 not requiring further hospital admissions and 70.1% dying at home. The median follow-up time was 1.6 months (IQR: 0.5-2.9). The most used devices were venous ports (71.4%) and oxygen (49.4%); 53.5% of the patients received oncological support therapies. The most common symptoms were pain (91.8%) dyspnea (49.0%) and fatigue (46.9%). CONCLUSIONS: Home assistance was provided in a high number of patients, with a large proportion needing one or no hospital admissions and 70.1% of them dying at home. Further studies characterizing these patients and the factors which promote early access to palliative care are needed.

Donación en asistolia controlada. ¿Qué opinan los profesionales de cuidados intensivos pediátricos? / Donation after circulatory death. What is the opinion of pediatric intensive care professionals?

No disponible

Summary of Recommendations and Key Points of the Consensus of Spanish Scientific Societies (SEPAR, SEMICYUC, SEMES; SECIP, SENEO, SEDAR, SENP) on the Use of Non-Invasive Ventilation and High-Flow Oxygen Therapy with Nasal Cannulas in Adult, Pediatric, and Neonatal Patients With Severe Acute Respiratory Failure.

Non-invasive respiratory support (NIRS) in adult, pediatric, and neonatal patients with acute respiratory failure (ARF) comprises two treatment modalities, non-invasive mechanical ventilation (NIMV) and high-flow nasal cannula (HFNC) therapy. However, experts from different specialties disagree on the benefit of these techniques in different clinical settings. The objective of this consensus was to develop a series of good clinical practice recommendations for the application of non-invasive support in patients with ARF, endorsed by all scientific societies involved in the management of adult and pediatric/neonatal patients with ARF. To this end, the different societies involved were contacted, and they in turn appointed a group of 26 professionals with sufficient experience in the use of these techniques. Three face-to-face meetings were held to agree on recommendations (up to a total of 71) based on a literature review and the latest evidence associated with 3 categories: indications, monitoring and follow-up of NIRS. Finally, the experts from each scientific society involved voted telematically on each of the recommendations. To classify the degree of agreement, an analog classification system was chosen that was easy and intuitive to use and that clearly stated whether the each NIRS intervention should be applied, could be applied, or should not be applied.

Summary of Recommendations and Key Points of the Consensus of Spanish Scientific Societies (SEPAR, SEMICYUC, SEMES; SECIP, SENEO, SEDAR, SENP) on the Use of Non-Invasive Ventilation and High-Flow Oxygen Therapy with Nasal Cannulas in Adult, Pediatric, and Neonatal Patients With Severe Acute Respiratory Failure / Sumario de recomendaciones y puntos clave del Consenso de las Sociedades Científicas Españolas (SEPAR, SEMICYUC, SEMES; SECIP, SENeo, SEDAR, SENP) para la utilización de la ventilación no invasiva y terapia de alto flujo con cánulas nasales en el paciente adulto, pediátrico y neonatal con insuficiencia respiratoria aguda grave

Non-invasive respiratory support (NIRS) in adult, pediatric, and neonatal patients with acute respiratory failure (ARF) comprises two treatment modalities, non-invasive mechanical ventilation (NIMV) and high-flow nasal cannula (HFNC) therapy. However, experts from different specialties disagree on the benefit of these techniques in different clinical settings. The objective of this consensus was to develop a series of good clinical practice recommendations for the application of non-invasive support in patients with ARF, endorsed by all scientific societies involved in the management of adult and pediatric/neonatal patients with ARF.To this end, the different societies involved were contacted, and they in turn appointed a group of 26 professionals with sufficient experience in the use of these techniques. Three face-to-face meetings were held to agree on recommendations (up to a total of 71) based on a literature review and the latest evidence associated with 3 categories: indications, monitoring and follow-up of NIRS. Finally, the experts from each scientific society involved voted telematically on each of the recommendations. To classify the degree of agreement, an analog classification system was chosen that was easy and intuitive to use and that clearly stated whether the each NIRS intervention should be applied, could be applied, or should not be applied. (AU)

El soporte respiratorio no invasivo (SRNI) comprende 2 modalidades de tratamiento, la ventilación mecánica no invasiva (VMNI) y la terapia de alto flujo con cánulas nasales (TAFCN) que se aplican en pacientes adultos, pediátricos y neonatales con insuficiencia respiratoria aguda (IRA). Sin embargo, el grado de acuerdo entre las distintas especialidades sobre el beneficio de estas técnicas en diferentes escenarios clínicos es controvertido. El objetivo del presente consenso fue elaborar una serie de recomendaciones de buena práctica clínica para la aplicación de soporte no invasivo en pacientes con IRA, avaladas por todas las sociedades científicas involucradas en el manejo del paciente adulto y pediátrico/neonatal con IRA.Para ello se contactó con las diferentes sociedades implicadas, quienes designaron a su vez a un grupo de 26 profesionales con suficiente experiencia en su aplicación. Se realizaron 3 reuniones presenciales para consensuar las recomendaciones (hasta un total de 71) fundamentadas en la revisión de la literatura y en la actualización de la evidencia disponible en relación con 3 categorías: indicaciones, monitorización y seguimiento del SRNI. Finalmente, se procedió a votación telemática de cada una de las recomendaciones, por parte de los expertos de cada sociedad científica implicada. Para la clasificación del grado de acuerdo se optó por un sistema analógico de clasificación fácil e intuitivo de usar, y que expresara con claridad si el procedimiento relacionado con el SRNI debía hacerse, podía hacerse o no debía hacerse. (AU)

The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity.

The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into the epidemiology of COVID-19, important questions remain about the clinical complexities and underlying mechanisms of disease phenotypes. Severe COVID-19 most commonly involves respiratory manifestations, although other systems are also affected, and acute disease is often followed by protracted complications. Such complex manifestations suggest that SARS-CoV-2 dysregulates the host response, triggering wide-ranging immuno-inflammatory, thrombotic, and parenchymal derangements. We review the intricacies of COVID-19 pathophysiology, its various phenotypes, and the anti-SARS-CoV-2 host response at the humoral and cellular levels. Some similarities exist between COVID-19 and respiratory failure of other origins, but evidence for many distinctive mechanistic features indicates that COVID-19 constitutes a new disease entity, with emerging data suggesting involvement of an endotheliopathy-centred pathophysiology. Further research, combining basic and clinical studies, is needed to advance understanding of pathophysiological mechanisms and to characterise immuno-inflammatory derangements across the range of phenotypes to enable optimum care for patients with COVID-19.