OBJECTIVE:This study aimed to identify early clinical predictors of non-invasive ventilation (NIV) failure in children with Pediatric Acute Respiratory Distress Syndrome (PARDS) and to develop a model to predict NIV outcomes. METHODS:A prospective observational study including children (0-15 years) who were supported by NIV and met PARDS criteria was performed in two public PICUs in Chile. Demographic, physiological variables, and clinical outcomes were recorded. Logistic regression was used to identify risk factors for NIV failure and develop a predictive model. RESULTS:Seventy-six patients were enrolled (median age 22 months [IQR 11-48]; weight 12.1 kg [9.6-18.3]). Eighteen patients (24%) failed NIV (Failure group), with a median NIV duration of 12.5 h (IQR 8-23.8). The Failure group showed a significant reduction in the SpO2/FiO2 ratio after 2 h of NIV (-59 [-124 to 5] vs -2 [-49 to 30], p = 0.03). In multivariate analysis, an increase in ΔSpO2/FiO2 (improvement in oxygenation) was associated with lower odds of NIV failure (OR 0.98; 95% CI 0.97-0.99; p = 0.006), indicating that worsening oxygenation was associated with a higher risk. The final prediction model included age and early changes in SpO2/FiO2, respiratory rate, and heart rate, demonstrating good discrimination (AUROC 0.764; 95% CI 0.641-0.888). CONCLUSION:In children with PARDS treated with NIV, a model including age and early changes in oxygenation, heart rate, and respiratory rate within the first 2 h predicts the need for intubation with good discrimination.

Rationale: Lung ultrasonography (US) may be useful for the prognostication of acute lung disease. Objectives: To assess whether the lung US score is associated with the severity of lung disease and may predict prolonged invasive mechanical ventilation (IMV) in critically ill children. Methods: Prospective observational multicenter study in children aged 1 month to 18 years who required respiratory support in the ICU. Children with chronic parenchymal lung disease were excluded. The lung US score was obtained at 12 hours and 48-72 hours after admission. Prolonged IMV was defined as at least 7 consecutive days. Correlation of the lung US score with oxygenation as well as its prognostic accuracy for prolonged IMV were investigated. Measurements and Main Results: A total of 538 children were included, and 62 (11.5%) required prolonged mechanical ventilation. In these subjects, the lung US score was higher at 12 (median, 24 [IQR, 19-26] vs. 8 [3-14]; P < 0.001) and 48-72 hours (16 [10.5-22.5] vs. 6 [3-11]; P < 0.001). At 12 hours, the lung US score correlated with oxygenation index (R2 = 0.435 [95% CI, 0.293-0.566]; ρ coefficient, -0.705; P < 0.001) and oxygen saturation index (R2 = 0.499 [95% CI, 0.370-0.613]; ρ coefficient, 0.651; P < 0.001). The lung US score at 12 hours had good accuracy in predicting prolonged IMV (area under the receiver operating characteristic curve [AUROC], 0.87; 95% CI, 0.81-0.93), and its use in a multivariable model had excellent accuracy in derivation (AUROC, 0.92; 95% CI, 0.89-0.95) and internal validation (AUROC, 0.91; 95% CI, 0.90-0.92). Conclusions: In critically ill children, the lung US score early after admission may predict prolonged IMV.

Aim: Recent emergence of airway clearance devices (ACDs) as a treatment alternative for foreign body airway obstructions (FBAO) lacks substantial evidence on efficacy and safety. This study aimed to assess pediatric residents' knowledge and skills in managing a simulated pediatric choking scenario, adhering to recommended protocols, and using LifeVac (c) and DeCHOKER (c) ACDs. Methods: Randomized controlled simulation trial, in which 60 pediatric residents from 3 different hospitals (median age 27 [25.0-29.9]; 76.7% female) were asked to solve an unannounced pediatric simulated choking scenario using three interventions to manage (randomized order): 1) following the recommended protocol of the European Resuscitation Council (encouraging to cough or combination of back blows and abdominal thrusts); 2) using LifeVac (c); and 3) using DeCHOKER (c). A Little Anne QCPR (TM) manikin (Laerdal Medical) was used. The variable compliance rate (%) was calculated according to the correct/incorrect execution of the steps constituting the proper actions for each test. Results: Participants demonstrated a correct compliance rate only ranging between 50-75% in following the recommended protocol for managing partial FBAO progressing to severe. Despite unfamiliarity with the ACDs, pediatric residents achieved rates between 75% and 100%, with no significant difference noted between the two devices (p = 0.173). Both scenarios were successfully resolved in under a minute, with LifeVac (c) demonstrating a significantly shorter response time compared to DeCHOKER (c) (39.2 [30.4-49.1] vs. 45.1s [33.7-59.2], p = 0.010). Conclusions: Only a minority of pediatric residents were able to adhere to the recommended FBAO protocol, whereas 70% of them were able to adequately use the ACDs. However, since a significant proportion could not, it seems that ACDs themselves do not address all issues.

El edema cerebral fulminante agudo (AFCE) es un cuadro clínico dentro de las encefalitis con una evolución rápidamente progresiva de aparición en la edad pediátrica y que se asocia a una importante morbimortalidad.Presentamos un caso clínico que cursa con crisis comiciales, deterioro neurológico rápido y la aparición precoz de signos de herniación cerebral. Aunque las pruebas radiológicas fueron normales inicialmente y no hay establecidos parámetros que predigan la evolución de encefalitis a un subtipo rápidamente progresiva, la evolución clínica que presentó obligó a la realización de una craniectomía descompresiva ante la falta de respuesta al manejo médico del edema cerebral. En ocasiones puede ser necesario la toma de una biopsia cerebral para llegar al diagnóstico de la causa que ha producido la encefalitis origen del edema cerebral agudo fulminante. El objetivo de la cirugía debe ser no solo el aumento de la supervivencia, sino la disminución de las secuelas neurológicas posteriores.

Objectives (1) To assess how main pulmonary artery peak Doppler velocity (MPAVpeak) correlates with right ventricular output (RVO) and superior vena cava flow (SVCf), (2) to assess the reproducibility of MPAVpeak and (3) to test the prognostic accuracy of MPAVpeak to predict high-grade intraventricular haemorrhage (IVH) or death at seventh day of life. Design Prospective cohort study. Setting Nine third-level neonatal units in Spain. Patients Preterm infants <33 weeks of gestational age who had standardised measurements of MPAVpeak, RVO and SVCf at 6, 12 and 24 hours of life. Main outcome measures High-grade IVH or death at seventh day of life. Results One hundred and ninety preterm infants with a median (IQR) gestational age and birth weight of 29.7 weeks (27.1-31.8) and 1152 g (892-1491), respectively, were included. High-grade IVH or death at seventh day of life occurred in 24 (12.6%). MPAVpeak was strongly correlated with RVO (Spearman rho 0.826-0.843). MPAVpeak discriminated well for low RVO (<120 mL/kg/min) at 6 (AUROC, area under the receiver operating characteristic curve=0.90), 12 (AUROC 0.94) and 24 hours (AUROC 0.86). Observer reproducibility was better for MPAVpeak (inter-observer limits of agreement +/- 8.4%) compared with RVO (+/- 18.8%) and SVCf (+/- 32.2%). The prognostic accuracy of MPAVpeak to predict high-grade IVH or death was good (AUROC >0.75) and non-inferior to RVO and SVCf (DeLong's test p>0.05). Conclusions MPAVpeak is an adequate marker of systemic blood flow with high reproducibility and acceptable prognostic accuracy in preterm infants below 33 weeks of gestational age during the first day of life.

OBJECTIVE:To determine whether early echocardiography screening of low systemic blood flow reduces intraventricular hemorrhage in preterm infants. STUDY DESIGN:Prospective multicenter study in preterm infants below 33 weeks of gestational age at nine neonatal units. Five units performed early echocardiography screening for low systemic blood flow and guided clinical management (exposure group) and 4 units did not (control group). Our main outcome was ≥grade II intraventricular hemorrhage or death within the first 7 days of life. The main analysis used the inverse probability of treatment weighting. RESULTS:Three hundred and thirty-two preterm infants (131 in the exposure group and 201 in the control group) were included. Exposure to early echocardiography screening was associated with a significant reduction in ≥grade II intraventricular hemorrhage or early death [odds ratio 0.285 (95% CI: 0.133-0.611); p = 0.001]. CONCLUSIONS:Early echocardiography screening for low systemic blood flow may reduce the incidence of intraventricular hemorrhage in preterm infants.

BACKGROUND:The aim of the present study was to develop a clinical-ultrasound model for early detection of hospital admission, pediatric intensive care unit (PICU) admission, and oxygen requirement in children diagnosed with acute bronchiolitis (AB). Furthermore, the prognostic ability of models including sonographic data from antero-lateral, lateral-posterior, and posterior areas (eight zones) vs. antero-lateral and lateral-posterior areas (six zones) vs. only antero-lateral areas (four zones) was analyzed. METHODS:A prospective study was conducted on infants under 12 months with AB. A lung ultrasound (LUS) was performed within 24 h of hospital care and analyzed using the Lung Ultrasound Combined Score (LUCS) based on the ultrasound patterns and their extent. Regression models combining LUCS (using eight, six, or four lung areas) with age and clinical scale were created. RESULTS:A total of 90 patients were included (62 admitted to the ward, 15 to PICU), with a median age of 3.7 months. Clinical-ultrasound models with eight and six lung zones predicted hospital admission (AUC 0.89), need for oxygen therapy (AUC 0.88), and its duration (40% explanatory capacity). Models using four lung areas had lower prognostic yield. No model predicted PICU admission needs or duration. CONCLUSIONS:The ultrasound pattern and its extension combined with clinical information may be useful to predict hospital admission and oxygen requirement.

Acute fulminant cerebral edema is a type of rapidly progressive encephalitis that occurs in children and is associated with significant morbidity and mortality.We present a clinical case with seizures, rapid neurological deterioration and the early appearance of cerebral herniation signs. Although the radiological tests were initially normal and there are no established parameters that predict the evolution of encephalitis to a rapidly progressive subtype, the clinical evolution forced to consider the decompressive craniectomy due to the lack of response to the medical management of the cerebral edema. It may be necessary take a brain biopsy to confirm the etiology of the encephalitis origin of acute fulminant cerebral edema. The objective of surgery should be not only to increase survival, but also to reduce subsequent neurological sequelae.

Abstract Background The objective of this study was to analyze the effects of sedation administration on clinical parameters, comfort status, intubation requirements, and the pediatric intensive care unit (PICU) length of stay (LOS) in children with acute respiratory failure (ARF) receiving noninvasive ventilation (NIV). Methods Thirteen PICUs in Spain participated in a prospective, multicenter, observational trial from January to December 2021. Children with ARF under the age of five who were receiving NIV were included. Clinical information and comfort levels were documented at the time of NIV initiation, as well as at 3, 6, 12, 24, and 48 h. The COMFORT-behavior (COMFORT-B) scale was used to assess the patients’ level of comfort. NIV failure was considered to be a requirement for endotracheal intubation. Results A total of 457 patients were included, with a median age of 3.3 months (IQR 1.3–16.1). Two hundred and thirteen children (46.6%) received sedation (sedation group); these patients had a higher heart rate, higher COMFORT-B score, and lower SpO2/FiO2 ratio than did those who did not receive sedation (non-sedation group). A significantly greater improvement in the COMFORT-B score at 3, 6, 12, and 24 h, heart rate at 6 and 12 h, and SpO2/FiO2 ratio at 6 h was observed in the sedation group. Overall, the NIV success rate was 95.6%-intubation was required in 6.1% of the sedation group and in 2.9% of the other group (p = 0.092). Multivariate analysis revealed that the PRISM III score at NIV initiation (OR 1.408; 95% CI 1.230–1.611) and respiratory rate at 3 h (OR 1.043; 95% CI 1.009–1.079) were found to be independent predictors of NIV failure. The PICU LOS was correlated with weight, PRISM III score, respiratory rate at 12 h, SpO2 at 3 h, FiO2 at 12 h, NIV failure and NIV duration. Sedation use was not found to be independently related to NIV failure or to the PICU LOS. Conclusions Sedation use may be useful in children with ARF treated with NIV, as it seems to improve clinical parameters and comfort status but may not increase the NIV failure rate or PICU LOS, even though sedated children were more severe at technique initiation in the present sample.

The objective of this study was to analyze the effects of sedation administration on clinical parameters, comfort status, intubation requirements, and the pediatric intensive care unit (PICU) length of stay (LOS) in children with acute respiratory failure (ARF) receiving noninvasive ventilation (NIV). Thirteen PICUs in Spain participated in a prospective, multicenter, observational trial from January to December 2021. Children with ARF under the age of five who were receiving NIV were included. Clinical information and comfort levels were documented at the time of NIV initiation, as well as at 3, 6, 12, 24, and 48 h. The COMFORT-behavior (COMFORT-B) scale was used to assess the patients’ level of comfort. NIV failure was considered to be a requirement for endotracheal intubation. A total of 457 patients were included, with a median age of 3.3 months (IQR 1.3–16.1). Two hundred and thirteen children (46.6

OBJECTIVES: The worldwide practice and impact of noninvasive ventilation (NIV) in pediatric acute respiratory distress syndrome (PARDS) is unknown. We sought to describe NIV use and associated clinical outcomes in PARDS.DESIGN: Planned ancillary study to the 2016/2017 prospective Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study.SETTING: One hundred five international PICUs.PATIENTS: Patients with newly diagnosed PARDS admitted during 10 study weeks.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Children were categorized by their respiratory support at PARDS diagnosis into NIV or invasive mechanical ventilation (IMV) groups. Of 708 subjects with PARDS, 160 patients (23%) received NIV at PARDS diagnosis (NIV group). NIV failure rate (defined as tracheal intubation or death) was 84 of 160 patients (53%). Higher nonrespiratory pediatric logistic organ dysfunction (PELOD-2) score, Pao(2)/Fio(2) was less than 100 at PARDS diagnosis, immunosuppression, and male sex were independently associated with NIV failure. NIV failure was 100% among patients with nonrespiratory PELOD-2 score greater than 2, Pao(2)/Fio(2) less than 100, and immunosuppression all present. Among patients with Pao(2)/Fio(2) greater than 100, children in the NIV group had shorter total duration of NIV and IMV, than the IMV at initial diagnosis group. We failed to identify associations between NIV use and PICU survival in a multivariable Cox regression analysis (hazard ratio 1.04 [95% CI, 0.61-1.80]) or mortality in a propensity score matched analysis (p = 0.369).CONCLUSIONS: Use of NIV at PARDS diagnosis was associated with shorter exposure to IMV in children with mild to moderate hypoxemia. Even though risk of NIV failure was high in some children, we failed to identify greater hazard of mortality in these patients.

Background: Variants in IFIH1, a gene coding the cytoplasmatic RNA sensor MDA5, regulate the response to viral infections. We hypothesized that IFIH1 rs199076 variants would modulate host response and outcome after severe COVID-19. Methods: Patients admitted to an intensive care unit (ICU) with confirmed COVID-19 were prospectively studied and rs1990760 variants determined. Peripheral blood gene expression, cell populations, and immune mediators were measured. Peripheral blood mononuclear cells from healthy volunteers were exposed to an MDA5 agonist and dexamethasone ex-vivo, and changes in gene expression assessed. ICU discharge and hospital death were modeled using rs1990760 variants and dexamethasone as factors in this cohort and in-silico clinical trials. Results: About 227 patients were studied. Patients with the IFIH1 rs1990760 TT variant showed a lower expression of inflammation-related pathways, an anti-inflammatory cell profile, and lower concentrations of pro-inflammatory mediators. Cells with TT variant exposed to an MDA5 agonist showed an increase in IL6 expression after dexamethasone treatment. All patients with the TT variant not treated with steroids survived their ICU stay (hazard ratio [HR]: 2.49, 95% confidence interval [CI]: 1.29–4.79). Patients with a TT variant treated with dexamethasone showed an increased hospital mortality (HR: 2.19, 95% CI: 1.01–4.87) and serum IL-6. In-silico clinical trials supported these findings. Conclusions: COVID-19 patients with the IFIH1 rs1990760 TT variant show an attenuated inflammatory response and better outcomes. Dexamethasone may reverse this anti-inflammatory phenotype. Funding: Centro de Investigación Biomédica en Red (CB17/06/00021), Instituto de Salud Carlos III (PI19/00184 and PI20/01360), and Fundació La Marató de TV3 (413/C/2021).

Bermúdez Barrezueta, L.1; Pons Ódena, M.2; Miñambres Rodríguez, M.3; Vivanco Allende, A.4; Valencia Ramos, J.5; López Fernández, Y.6; Palacios Cuesta, A.7; Reyes Domínguez, S.3; Mayordomo Colunga, J.4; García Teresa, M. A.8; Unzueta Roch, J. L.8; López González, J.9; Fernández Lafever, S.9; Oviedo Melgares, L.7; Artacho González, L.10; Gorostizaga, Z.6; Brezmes Raposo, M.1; González Gómez, J. M.10; Mendizabal Diez, M.11; Cuervas Mons Tejedor, M.5; Jiménez Villalta, M. T.12; González Salas, E.13; Gutiérrez Marqués, S.14; Trastoy Quintela, J.15 Author Information

Introduction The mortality risk in children admitted to Pediatric Intensive Care Units (PICU) is usually estimated by means of validated scales, which only include objective data among their items. Human perceptions may also add relevant information to prognosticate the risk of death, and the tool to use this subjective data is fuzzy logic. The objective of our study was to develop a mathematical model to predict mortality risk based on the subjective perception of PICU staff and to evaluate its accuracy compared to validated scales. Methods A prospective observational study in two PICUs (one in Spain and another in Latvia) was performed. Children were consecutively included regardless of the cause of admission along a two-year period. A fuzzy set program was developed for the PICU staff to record the subjective assessment of the patients' mortality risk expressed through a short range and a long range, both between 0% and 100%. Pediatric Index of Mortality 2 (PIM2) and Therapeutic Intervention Scoring System 28 (TISS28) were also prospectively calculated for each patient. Subjective and objective predictions were compared using the logistic regression analysis. To assess the prognostication ability of the models a stratified B-random K-fold cross-validation was performed. Results Five hundred ninety-nine patients were included, 308 in Spain (293 survivors, 15 nonsurvivors) and 291 in Latvia (282 survivors, 9 nonsurvivors). The best logistic classification model for subjective information was the one based on MID (midpoint of the short range), whereas objective information was the one based on PIM2. Mortality estimation performance was 86.3% for PIM2, 92.6% for MID, and the combination of MID and PIM2 reached 96.4%. Conclusions Subjective assessment was as useful as validated scales to estimate the risk of mortality. A hybrid model including fuzzy information and probabilistic scales (PIM2) seems to increase the accuracy of prognosticating mortality in PICU.

People with a reduced nighttime dip in blood pressure have an increased cardiovascular risk. Our objective was to describe the different patterns in blood pressure (BP) among pediatricians who work in long on-duty shifts in relation with sex, medical rank and sleeping time. Descriptive, cross-sectional, two-center study. On duty pediatric Resident physicians and pediatric Consultants were recruited between January 2018 and December 2021. Fifty-one physicians were included in the study (78.4% female, 66.7% Resident physicians). Resident physicians had a higher night/day ratio (0.91 vs 0.85; p < 0.001) and a shorter nighttime period (3.87 vs 5.41, p < 0.001) than Consultants. Physicians sleeping less than 5 h had a higher night/day ratio (0.91 vs 0.87, p = 0.014). Being a Resident showed a ∼4.5-fold increased risk of having a non-dipping BP pattern compared to Consultants. We found a potential link between both being a Resident and, probably, having shorter sleeping time, and the non-dipping BP pattern in physicians during prolonged shifts. Las personas con un descenso nocturno reducido de la presión arterial tienen mayor riesgo cardiovascular. Nuestro objetivo fue describir los diferentes patrones de presión arterial en los pediatras que trabajan de guardia con presencia física, en relación con el sexo, la categoría profesional y el tiempo de sueño. Se realizó un estudio descriptivo, transversal, bicéntrico. Se reclutó a médicos residentes y adjuntos de pediatría, de guardia con presencia física, entre enero de 2018 y diciembre de 2021. Fueron incluidos en el estudio 51 médicos (78,4% mujeres; 66,7% médicos residentes). Los médicos residentes presentaron un cociente de presión arterial noche/día mayor (0,91 vs. 0,85; p < 0,001) y un tiempo de sueño menor (3,87 vs. 5,41; p < 0,001) que los adjuntos. Los participantes que durmieron menos de 5 horas presentaron un cociente de presión arterial noche/día mayor (0,91 vs. 0,87; p = 0,014). Ser médico residente demostró tener aumentado el riesgo de presentar un patrón no dipper en más de 4,5 veces respecto a los médicos adjuntos. Encontramos un vínculo potencial entre ser médico residente y, probablemente, tener menos horas de sueño, y el patrón de no descenso nocturno de la presión arterial en los médicos durante las guardias de presencia física.

A previously healthy 12-year-old boy had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related multisystem inflammatory syndrome (MIS-C) that was rapidly fatal. Autopsy revealed the presence of a large intracardiac thrombus. SARS-CoV-2 spike protein was detected in intestinal cells, supporting the hypothesis that viral presence in the gut may be related to the immunologic response of MIS-C.

Background:Cat scratch disease (CSD) is an infectious disorder caused by Bartonella henselae. The infection usually presents as local lymphadenopathy, fever, and mild constitutional symptoms. Systemic or severe disease is reported in 5-20% of patients with CSD. We report a case of disseminated CSD with osteomyelitis and hepatosplenic disease and a review of the literature.Case report:A previously healthy 5-year-old male presented with prolonged fever and abdominal pain, followed by low back pain. The serologic test showed positive IgG for B. henselae and IgM and IgG for Epstein Barr virus (EBV). The abdominal ultrasound showed hepatic and splenic hypoechoic lesions, and the magnetic resonance imaging (MRI) revealed spondylitis of the D6 vertebra. He received treatment with azithromycin for 4 weeks and rifampicin for 6 weeks. The symptoms disappeared, and the abdominal ultrasound was normal nine months later.Conclusions:Disseminated CSD is infrequent. The diagnosis requires a high rate of suspicion. Laboratory findings of Bartonella infection are often non-specific. Serologic test, polymerase chain reaction of B. henselae in blood or biopsied material of the site of involvement and imaging test can be performed to confirm the diagnosis. The diagnosis of disseminated B. henselae was based on significantly elevated blood titers, radiologic findings, and epidemiologic history. Treatment of CSD depends on the disease presentation. Azithromycin is used as a first-line agent for lymphadenopathy. The optimum treatment and its duration have not been established in atypical or complicated CSD, including patients with osteomyelitis and hepatosplenic disease.

Background Mechanical stretch of cancer cells can alter their invasiveness. During mechanical ventilation, lungs may be exposed to an increased amount of stretch, but the consequences on lung tumours have not been explored. Methods To characterise the influence of mechanical ventilation on the behaviour of lung tumours, invasiveness assays and transcriptomic analyses were performed in cancer cell lines cultured in static conditions or under cyclic stretch. Mice harbouring lung melanoma implants were submitted to mechanical ventilation and metastatic spread was assessed. Additional in vivo experiments were performed to determine the mechanodependent specificity of the response. Incidence of metastases was studied in a cohort of lung cancer patients that received mechanical ventilation compared with a matched group of nonventilated patients. Results Stretch increases invasiveness in melanoma B16F10luc2 and lung adenocarcinoma A549 cells. We identified a mechanosensitive upregulation of pathways involved in cholesterol processing in vitro, leading to an increase in pro-protein convertase subtilisin/kexin type 9 (PCSK9) and LDLR expression, a decrease in intracellular cholesterol and preservation of cell stiffness. A course of mechanical ventilation in mice harbouring melanoma implants increased brain and kidney metastases 2 weeks later. Blockade of PCSK9 using a monoclonal antibody increased cell cholesterol and stiffness and decreased cell invasiveness in vitro and metastasis in vivo. In patients, mechanical ventilation increased PCSK9 abundance in lung tumours and the incidence of metastasis, thus decreasing survival. Conclusions Our results suggest that mechanical stretch promote invasiveness of cancer cells, which may have clinically relevant consequences. Pharmacological manipulation of cholesterol endocytosis could be a novel therapeutic target in this setting.

Point of Care Ultrasound (POCUS) refers to the use of portable ultrasound (US) applications at the bedside, performed directly by the treating physician, for either diagnostic or procedure guidance purposes. It is being rapidly adopted by traditionally non-imaging medical specialties across the globe. Recent international evidence-based guidelines on POCUS for critically ill neonates and children were issued by the POCUS Working Group of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC). Currently there are no standardized national or international guidelines for its implementation into clinical practice or even the training curriculum to monitor quality assurance. Further, there are no definitions or methods of POCUS competency measurement across its varied clinical applications.The Hippocratic Oath suggests medical providers do no harm to their patients. In our continued quest to uphold this value, providers seeking solutions to clinical problems must often weigh the benefit of an intervention with the risk of harm to the patient. Technologies to guide diagnosis and medical management present unique considerations when assessing possible risk to the patient. Frequently risk extends beyond the patient and impacts providers and the institutions in which they practice. Point-of-care ultrasound (POCUS) is an emerging technology increasingly incorporated in the care of children across varied clinical specialties. Concerns have been raised by clinical colleagues and regulatory agencies regarding appropriate POCUS use and oversight. We present a framework for assessing the risk of POCUS use in pediatrics and suggest methods of mitigating risk to optimize safety and outcomes for patients, providers and institutions.

Rationale: Outcomes in patients with severe SARS-CoV-2 infection (COVID-19) are conditioned by virus clearance and regulation of inflammation. Variants in IFIH1, a gene coding the cytoplasmatic RNA sensor MDA5, regulate the response to viral infections. Objective: To characterize the impact of IFIH1 rs199076 variants on host response and outcomes after severe COVID-19. Methods: Patients admitted to an intensive care unit (ICU) with confirmed COVID-19 were prospectively studied and rs1990760 variants determined. Peripheral blood gene expression, cell populations and immune mediators were measured. Peripheral blood mononuclear cells from healthy volunteers were exposed to an MDA5 agonist and dexamethasone ex-vivo, and changes in gene expression assessed. ICU discharge and hospital death were modelled using rs1990760 variants and dexamethasone as factors in this cohort and in-silico clinical trials. Measurements and Main Results: 227 patients were studied. Patients with the IFIH1 rs1990760 TT variant showed a lower expression of inflammation-related pathways, an anti-inflammatory cell profile and lower concentrations of pro-inflammatory mediators. Cells with TT variant exposed to a MDA5 agonist showed an increase in IL6 expression after dexamethasone treatment. All patients with the TT variant not treated with steroids (N=14) survived their ICU stay (HR 2.49, 95% confidence interval 1.29-4.79). Patients with a TT variant treated with dexamethasone (N=50) showed an increased hospital mortality (HR 2.19, 95% confidence interval 1.01-4.87) and serum IL-6. In-silico clinical trials supported these findings. Conclusions: COVID-19 patients with the IFIH1 rs1990760 TT variant show an attenuated inflammatory response and better outcomes. Dexamethasone may reverse this anti-inflammatory phenotype.