The Clinical Pulmonary Infection Score Combined with Procalcitonin and Lung Ultrasound (CPIS-PLUS), a Good Tool for Ventilator Associated Pneumonia Early Diagnosis in Pediatrics.

Ventilator-associated pneumonia (VAP) is common in Pediatric Intensive Care Units. Although early detection is crucial, current diagnostic methods are not definitive. This study aimed to identify lung ultrasound (LUS) findings and procalcitonin (PCT) values in pediatric patients with VAP to create a new early diagnosis score combined with the Clinical Pulmonary Infection Score (CPIS), the CPIS-PLUS score. Prospective longitudinal and interventional study. Pediatric patients with suspected VAP were included and classified into VAP or non-VAP groups, based on Centers of Disease Control (CDC) criteria for the final diagnosis. A chest-X-ray (CXR), LUS, and blood test were performed within the first 12 h of admission. CPIS score was calculated. A total of 108 patients with VAP suspicion were included, and VAP was finally diagnosed in 51 (47%) patients. CPIS-PLUS showed high accuracy in VAP diagnosis with a sensitivity (Sn) of 80% (95% CI 65-89%) and specificity (Sp) of 73% (95% CI 54-86%). The area under the curve (AUC) resulted in 0.86 for CPIS-PLUS vs. 0.61 for CPIS. In conclusion, this pilot study showed that CPIS-PLUS could be a potential and reliable tool for VAP early diagnosis in pediatric patients. Internal and external validations are needed to confirm the potential value of this score to facilitate VAP diagnosis in pediatric patients.

Premature newborns with intraventricular hemorrhage do not have vasospasm pattern by cranial Doppler ultrasound: A pilot study.

Preterm neonates are at risk for neurodevelopmental impairment, especially those with intraventricular hemorrhage (IVH). Cerebral vasospasm (VSP) is a common complication after subarachnoid hemorrhage (SAH) in adult population, but it is unknown if preterm neonates with IVH may develop it. We prospectively enrolled premature newborns < 32 weeks with IVH and without IVH. All patients received serial transcranial sonography through the temporal window of the middle cerebral artery, anterior cerebral artery, posterior cerebral artery, and the internal carotid artery with transcranial Doppler sonography days 2, 4, and 10 of life. Cerebral blood velocities (CBFVs) were measured including median velocity flow (MV), peak systolic velocity (PSV), and maximum end-diastolic velocity (EDV). Resistance index and pulsatility index were calculated. VSP was defined as an increase of 50% in the baseline velocity per day and/or a Lindegaard ratio higher than 3. Fifty subjects were enrolled. None of the patients with IVH showed elevation of MV or a Lindegaard ratio > 3. There were no differences between IVH and without IVH groups regarding resistance index and pulsatility index.    Conclusion: Preterm infants with IVH do not present a pattern of VSP analyzed by Doppler transcranial ultrasound in this pilot study. What is Known: • In adult population with subarachnoid hemorrhage the most treatable cause of cerebral ischemia is due cerebral vasospasm but is unknown if premature newborn may have vasospasm due the extravasation of blood in the context of intraventricular hemorrhage What is New: •In this pilot study we did not find in premature newborn with intraventricular hemorrhage signs of vasoespam measured by transcranial color doppler ultrasound.

Lung ultrasound and procalcitonin, improving antibiotic management and avoiding radiation exposure in pediatric critical patients with bacterial pneumonia: a randomized clinical trial.

BACKGROUND: Pneumonia is a major public health problem with an impact on morbidity and mortality. Its management still represents a challenge. The aim was to determine whether a new diagnostic algorithm combining lung ultrasound (LUS) and procalcitonin (PCT) improved pneumonia management regarding antibiotic use, radiation exposure, and associated costs, in critically ill pediatric patients with suspected bacterial pneumonia (BP). METHODS: Randomized, blinded, comparative effectiveness clinical trial. Children < 18y with suspected BP admitted to the PICU from September 2017 to December 2019, were included. PCT was determined at admission. Patients were randomized into the experimental group (EG) and control group (CG) if LUS or chest X-ray (CXR) were done as the first image test, respectively. Patients were classified: 1.LUS/CXR not suggestive of BP and PCT < 1 ng/mL, no antibiotics were recommended; 2.LUS/CXR suggestive of BP, regardless of the PCT value, antibiotics were recommended; 3.LUS/CXR not suggestive of BP and PCT > 1 ng/mL, antibiotics were recommended. RESULTS: 194 children were enrolled, 113 (58.2%) females, median age of 134 (IQR 39-554) days. 96 randomized into EG and 98 into CG. 1. In 75/194 patients the image test was not suggestive of BP with PCT < 1 ng/ml; 29/52 in the EG and 11/23 in the CG did not receive antibiotics. 2. In 101 patients, the image was suggestive of BP; 34/34 in the EG and 57/67 in the CG received antibiotics. Statistically significant differences between groups were observed when PCT resulted < 1 ng/ml (p = 0.01). 3. In 18 patients the image test was not suggestive of BP but PCT resulted > 1 ng/ml, all of them received antibiotics. A total of 0.035 mSv radiation/patient was eluded. A reduction of 77% CXR/patient was observed. LUS did not significantly increase costs. CONCLUSIONS: Combination of LUS and PCT showed no risk of mistreating BP, avoided radiation and did not increase costs. The algorithm could be a reliable tool for improving pneumonia management. CLINICAL TRIAL REGISTRATION: NCT04217980.

Predictores del estado de salud funcional posingreso en cuidados intensivos en pacientes sépticos / Predictors of Post-Admission Functional Health Status in Intensive Care in Septic Patients

Introducción: Los pacientes críticos pediátricos son susceptibles de presentar alteraciones del flujo sanguíneo cerebral que impliquen un deterioro de su estado de salud funcional. Objetivo: Identificar factores predictores de mayor riesgo de mala evolución funcional en pacientes pediátricos críticos con sepsis. Métodos: Se realizó un estudio de cohortes retrospectivo con menores de 18 años de edad con sepsis, ingresados en la unidad de cuidados intensivos pediátricos. Se recogieron variables epidemiológicas, clínicas y del estado de salud funcional previas al ingreso, al alta y a los 6 meses. El estado de salud funcional se evaluó mediante la escala de categorías de estado global y cerebral pediátrico. Se evaluó el cambio del estado funcional entre el ingreso y a los 6 meses del alta. Se realizó un análisis univariante para comparar grupos considerando el mal pronóstico y el cambio del estado funcional y su relación con las variables. Resultados: Se incluyeron 46 pacientes. A los 6 meses del alta, cuatro (8,7 por ciento) presentaron mal pronóstico funcional y ocho (17,4 por ciento) empeoramiento funcional respecto al ingreso. No se encontraron asociaciones entre las variables predictoras y la morbilidad, aunque se observó cierta tendencia en algunas como mayor soporte inotrópico (VIS > 20: 12,5 por ciento vs. 50 por ciento, p= 0,075), extracorpóreo y de reemplazo renal (25 por ciento vs. 2,6 por ciento, p= 0,074) y estancia hospitalaria más prolongada (50 por ciento vs. 15,8 por ciento , p= 0,055). Conclusiones: El soporte en la unidad de cuidados intensivos pediátricos no fue un predictor de morbilidad funcional en la muestra(AU)

Introduction: Critically ill pediatric patients are susceptible to cerebral blood flow alterations that imply a deterioration of their functional health status. Objective: To identify predictors of a higher risk of poor functional outcome in critically ill pediatric patients with sepsis. Methods: A retrospective cohort study was conducted with children under 18 years of age with sepsis, who were admitted to the pediatric intensive care unit. Epidemiological, clinical, and functional health status variables were collected prior to admission, discharge, and after 6 months. Functional health status was assessed using the Pediatric Global State and Brain Status Category Scale. The change in performance status between admission and 6 months after discharge was assessed. A univariate analysis was performed to compare groups considering poor prognosis and change in functional status and their relationship with the variables. Results: A total of 46 patients were included. At 6 months after discharge, four (8.7 percent) had a poor functional prognosis and eight (17.4 percent) had functional worsening at admission. No associations were found between the predictor variables and morbidity, although some trends were observed in some variables, such as greater inotropic support (SIV > 20: 12.5 percent vs. 50 percent, p = 0.075), extracorporeal and renal replacement (25 percent vs. 2.6 , percent p = 0.074), and longer hospital stay (50 percent vs. 15.8 percent , p = 0.055). Conclusions: Support in the pediatric intensive care unit was not a predictor of functional morbidity in the sample(AU)

Risk factors and outcome of Chimeric Antigen Receptor T-Cell patients admitted to Pediatric Intensive Care Unit: CART-PICU study.

Introduction: Chimeric antigen receptor (CAR)T-cell CD19 therapy is an effective treatment for relapsed/refractory B-cell acute lymphoblastic leukemia. It can be associated with life-threatening toxicities which often require PICU admission. Purpose: to describe clinical characteristics, treatment and outcome of these patients. Methods: Prospective observational cohort study conducted in a tertiary pediatric hospital from 2016-2021. Children who received CAR-T admitted to PICU were included. We collected epidemiological, clinical characteristics, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), treatment, length of stay and mortality. Results: CAR T-cells (4-1BB constructs) were infused in 59 patients. Twenty-four (40.7%) required PICU admission, length of stay was 4 days (IQR 3-6). Median age was 8.3 years (range 4-24). Patients admitted to PICU presented higher disease burden before infusion: 24% blasts in bone marrow (IQR 5-72) vs. 0 (0-6.9), p<0.001. No patients with <5% blasts were admitted to PICU. Main reasons for admissions were CRS (n=20, 83.3%) and ICANS (n=3, 12.5%). Fourteen patients (58.3%) required inotropic support, 14(58.3%) respiratory. Sixteen patients (66.6%) received tocilizumab, 10(41.6%) steroids, 6(25.0%) anakinra, and 5(20.8%) siltuximab. Ten patients (41.6%) presented neurotoxicity, six of them severe (ICANS 3-4). Two patients died at PICU (8.3%) because of refractory CRS-hemophagocytic lymphohistyocitosis (carHLH) syndrome. There were no significant differences in relapse rate after CAR-T in patients requiring PICU, it was more frequently CD19 negative (p=0.344). Discussion: PICU admission after CAR-T therapy was mainly due to CRS. Supportive treatment allowed effective management and high survival. Some patients presenting with carHLH, can suffer a fulminant course.

An Artificial Placenta Experimental System in Sheep: Critical Issues for Successful Transition and Survival up to One Week.

OBJECTIVE: To describe the development of an artificial placenta (AP) system in sheep with learning curve and main bottlenecks to allow survival up to one week. METHODS: A total of 28 fetal sheep were transferred to an AP system at 110-115 days of gestation. The survival goal in the AP system was increased progressively in three consecutive study groups: 1-3 h (n = 8), 4-24 h (n = 10) and 48-168 h (n = 10). Duration of cannulation procedure, technical complications, pH, lactate, extracorporeal circulation (EC) circuit flows, fetal heart rate, and outcomes across experiments were compared. RESULTS: There was a progressive reduction in cannulation complications (75%, 50% and 0%, p = 0.004), improvement in initial pH (7.20 ± 0.06, 7.31 ± 0.04 and 7.33 ± 0.02, p = 0.161), and increment in the rate of experiments reaching survival goal (25%, 70% and 80%, p = 0.045). In the first two groups, cannulation accidents, air bubbles in the extracorporeal circuit, and thrombotic complications were the most common cause of AP system failure. CONCLUSIONS: Achieving a reproducible experimental setting for an AP system is extremely challenging, time- and effort-consuming, and requires a highly multidisciplinary team. As a result of the learning curve, we achieved reproducible transition and survival up to 7 days. Extended survival requires improving instrumentation with custom-designed devices.

Thrombotic microangiopathies in critically ill children: The MATUCIP registry in Spain.

INTRODUCTION: Thrombotic microangiopathies (TMA) are rare diseases usually presenting with renal, haematological, neurologic and cardiovascular involvement and nonspecific but severe symptoms. A registry of TMA cases managed in Spanish paediatric intensive care units (the MATUCIP Registry) was established with the aim of gaining knowledge on their clinical characteristics, diagnosis and acute-phase treatment. METHODS: We conducted a prospective multicentre observational study in 20 paediatric intensive care units (PICUs) in Spain from January 2017 to December 2021 in children aged more than 1 month with TMAs, who were followed up through the discharge from the PICU. RESULTS: The sample included 97 patients (51.5% female) with a median age of 2.6 years (interquartile range [IQR], 1.6-5.7). The initial manifestations were gastrointestinal (74.2%), respiratory (14.4%), fever (5.2%), neurologic (3.1%) and other (3.1%). At admission, 75.3% of patients had microangiopathic haemolytic anaemia, 95.9% thrombocytopenia and 94.8% acute kidney injury. Of the total sample, 57.7% of patients received a diagnosis of Shiga toxin-associated haemolytic uraemic syndrome (HUS), 14.4% of Streptococcus pneumoniae-associated HUS, 15.6% of atypical HUS, 10.3% of secondary TMA and 2.1% of thrombotic thrombocytopenic purpura. Eighty-seven patients (89.7%) developed arterial hypertension, and 49.5% gastrointestinal, 22.7% respiratory, 25.8% neurologic and 12.4% cardiac manifestations. Also, 60.8% required renal replacement therapy and 2.1% plasma exchange. Twenty patients received eculizumab. The median PICU stay was 8.5 days (IQR, 5-16.5). Two children died. CONCLUSIONS: The MATUCIP registry demonstrates the clinical variability of TMA cases requiring admission to the PICU. Knowledge of the presentation and outcomes of TMAs can facilitate early aetiological diagnosis. This registry can help improve our understanding of the clinical spectrum of these diseases, for which there is a dearth of published data.

Quantification of a qualitative sepsis code: laying the foundations for the automation revolution.

To quantify a qualitative screening tool for the early recognition of sepsis in children with fever either visiting the emergency department or already admitted to hospital. Prospective observational study including febrile patients under 18 years of age. Sepsis diagnosis was the main outcome. A multivariable analysis was performed with 4 clinical variables (heart rate, respiratory rate, disability, and poor skin perfusion). The cut-off points, odds ratio, and coefficients of these variables were identified. The quantified tool was then obtained from the coefficients. The area under the curve (AUC) was obtained and internal validation was performed using k-fold cross-validation. Two hundred sixty-six patients were included. The multivariable regression confirmed the independent association of the 4 variables with the outcome. The quantified screening tool yielded an excellent AUC, 0.825 (95%CI 0.772-0.878, p < 0.001), for sepsis prediction.  Conclusion: We successfully quantified a sepsis screening tool, and the resulting model has an excellent discriminatory power. What is Known: • Screening tests have to be based only on clinical variables that needs minimum technological support. • The current Sepsis Code is a qualitative screening tool. What is New: • The current screening tool was quantified using four clinical variables, weighted according to the deviation from normality and differentiated according to the age of the patient. • The resulting model has an excellent discriminatory power in identifying septic patients among febrile pediatric patients.

Device Exposure and Patient Risk Factors' Impact on the Healthcare-Associated Infection Rates in PICUs.

Healthcare-associated infections related to device use (DA-HAIs) are a serious public health problem since they increase mortality, length of hospital stay and healthcare costs. We performed a multicenter, prospective study analyzing critically ill pediatric patients admitted to 26 Spanish pediatric intensive care units (PICUs) over a 3-month period each year from 2014 to 2019. To make comparisons and evaluate the influence of HAI Zero Bundles (care bundles that intend to reduce the DA-HAI rates to zero) on PICU HAI rates, the analysis was divided into two periods: 2014-2016 and 2017-2019 (once most of the units had incorporated all the Zero Bundles). A total of 11,260 pediatric patients were included. There were 390 episodes of HAIs in 317 patients and the overall rate of HAIs was 6.3 per 1000 patient days. The DA-HAI distribution was: 2.46/1000 CVC days for central-line-associated bloodstream infections (CLABSIs), 5.75/1000 MV days for ventilator-associated pneumonia (VAP) and 3.6/1000 UC days for catheter-associated urinary tract infections (CAUTIs). Comparing the two periods, the HAI rate decreased (p = 0.061) as well as HAI episodes (p = 0.011). The results demonstrate that exposure to devices constitutes an extrinsic risk factor for acquiring HAIs. The multivariate analysis highlights previous bacterial colonization by multidrug-resistant (MDR) bacteria as the most important extrinsic risk factor for HAIs (OR 20.4; 95%CI 14.3-29.1). In conclusion, HAI Zero Bundles have been shown to decrease HAI rates, and the focus should be on the prompt removal of devices, especially in children with important intrinsic risk factors.

A Review of Adrenomedullin in Pediatric Patients: A Useful Biomarker.

Adrenomedullin has several properties. It acts as a potent vasodilator, has natriuretic effects, and reduces endothelial permeability. It also plays a role in initiating the early hyperdynamic phase of sepsis. Since its discovery, many articles have been published studying the uses and benefits of this biomarker. The aim of this review is to determine the usefulness of adrenomedullin in pediatric patients. Relevant studies covering adrenomedullin in pediatrics (<18 years) and published up until August 2021 were identified through a search of MEDLINE, PubMed, Embase, Web of Science, Scopus, and Cochrane. Seventy studies were included in the present review, most of them with a low level of evidence (IV to VI). Research on adrenomedullin has primarily been related to infection and the cardiovascular field. The performance of adrenomedullin to quantify infection in children seems satisfactory, especially in sepsis. In congenital heart disease, this biomarker seems to be a useful indicator before, during, and after cardiopulmonary bypass. Adrenomedullin seems to be useful in the pediatric population for a large variety of pathologies, especially regarding infection and cardiovascular conditions. However, it should be used in combination with other biomarkers and clinical or analytical variables, rather than as a single tool.

Lung ultrasound to evaluate lung recruitment in neonates with respiratory distress (RELUS study).

BACKGROUND: Lung ultrasound (LUS) is a bedside tool useful to diagnose neonatal respiratory disease and to guide surfactant therapy. LUS scores have emerged as useful tool for newborn respiratory distress but is unknown if respiratory support settings may influence it. The aim of the study was to evaluate the feasibility of LUS scores evaluating lung recruitment in term newborns with respiratory distress when noninvasive respiratory it is increased. MATERIAL AND METHODS: Prospective study in a tertiary neonatal intensive care unit. Inclusion criteria were term neonates with respiratory distress requiring noninvasive respiratory support with nasal continuous positive airway pressure (nCPAP) within first 6 h of life with an LUS score higher than 8 were enrolled. LUS was performed three times. First LUS (LUS-1) was done in patients in nCPAP (Fabian Device) (Acutronic) (pressure of 6 cmH2 O). Afterwards patients were placed in duo positive airway pressure (12/6 cmH2 O), a second LUS (LUS-2) was performed immediately and a third (LUS-3) was done 2 h later on the same respiratory support. The primary outcome was to compare LUS scores in the different timelines. Second outcomes were to evaluate the level of respiratory distress and oxygenation were evaluated with SpO2 /fraction of inspired oxygen (FiO2 ) ratio (S/F ratio), FiO2  ratio, respiratory rate, and blood gas analysis which were analyzed during the LUS-1 and the LUS-3. To evaluate newborn discomfort, patients were evaluated with Crying Requires oxygen Increased vital signs Expression Sleep (CRIES) scale. RESULTS: Forty neonates were enrolled. Fifty percent were female (n = 20), median gestational age was 38 + 4 (interquartile range [IQR]: 37 + 5-39 + 4) with a median weight of 3155 g (IQR: 2637-3532). Duration of non invasive ventilation support was 72 h (IQR: 54-96). None of the patients required surfactant therapy or mechanical ventilation. LUS scores were no different between LUS-1 9 (IQR: 8.3-10) and LUS-2 9 (IQR: 8.3-10) (p = 0.675) but there were differences between LUS-1 and LUS-3 7 (IQR: 6.3-8.5) (p = 0.036). There was an improvement in the oxygen parameters, respiratory rate, and CO2 between LUS-1 and LUS-3 (p < 0.001). There were no changes in the CRIES scale. CONCLUSIONS: There is an improvement in clinical and laboratory parameters after the increasing of respiratory support in newborns with noninvasive ventilation. We observe a correlation with an improvement in the assessment of lung aeration were evaluated with LUS score.

Ventilator-associated pneumonia is linked to a worse prognosis than community-acquired pneumonia in children.

BACKGROUND: Around 12-20% of patients with community-acquired pneumonia (CAP) require critical care. Ventilator-associated pneumonia (VAP) is the second cause of nosocomial infection in Paediatric Intensive Care Units (PICU). As far as we know, there are no studies comparing both types of pneumonia in children, thus it remains unclear if there are differences between them in terms of severity and outcomes. OBJECTIVE: The aim was to compare clinical and microbiological characteristics and outcomes of patients with severe CAP and VAP. METHODS: A retrospective descriptive study, including patients diagnosed of VAP and CAP, with a positive respiratory culture and under mechanical ventilation, admitted to the PICU from 2015 to 2019. RESULTS: 238 patients were included; 163 (68.4%) with CAP, and 75 (31.5%) with VAP. Patients with VAP needed longer mechanical ventilation (14 vs. 7 days, p<0.001) and more inotropic support (49.3 vs. 30.7%, p = 0.006). Patients with VAP had higher mortality (12 vs. 2.5%, p = 0.005). Enterobacterales were more involved with VAP than with CAP (48 vs. 9%, p<0.001). Taking into account only the non-drug sensitive microorganisms, patients with VAP tended to have more multidrug-resistant bacteria (30 vs. 10.8%, p = 0.141) than patients with CAP. CONCLUSION: Patients with VAP had worse prognosis than patients with CAP, needing longer mechanical ventilation, more inotropic support and had higher mortality. Patients with VAP were mainly infected by Enterobacterales and had more multidrug resistant microorganisms than patients with CAP.

Antimicrobial Stewardship Improvement in Pediatric Intensive Care Units in Spain-What Have We Learned?

Antibiotic misuse in pediatric intensive care units (PICUs) can lead to increased antimicrobial resistance, antibiotic-triggered side effects, hospital costs, and mortality. We performed a multicenter, prospective study, analyzing critically ill pediatric patients (≥1 month to ≤18 years) admitted to 26 Spanish PICUs over a 3-month period each year (1 April−30 June) from 2014−2019. To make comparisons and evaluate the influence of AMS programs on antibiotic use in PICUs, the analysis was divided into two periods: 2014−2016 and 2017−2019 (once 84% of the units had incorporated an AMS program). A total of 11,260 pediatric patients were included. Total antibiotic prescriptions numbered 15,448 and, overall, 8354 patients (74.2%) received at least one antibiotic. Comparing the two periods, an increase was detected in the number of days without antibiotics in patients who received them divided by the number of days in PICUs, for community-acquired infections (p < 0.001) and healthcare-associated infections (HAIs) acquired in PICUs (p < 0.001). Antibiotics were empirical in 7720 infections (85.6%), with an increase in appropriate antibiotic indications during the second period (p < 0.001). The main indication for antibiotic adjustment was de-escalation, increasing in the second period (p = 0.045). Despite the high rate of antibiotic use in PICUs, our results showed a significant increase in appropriate antibiotic use and adjustment following the implementation of AMS programs.

RISK score for developing ventilator-associated pneumonia in children: The RISVAP study.

OBJECTIVES: Ventilator-associated pneumonia (VAP) is the second most common healthcare-associated infection in children. The aim of this study was to determine the risk factors for VAP in children and to create a risk score for developing VAP (RISVAP score). STUDY DESIGN: It was a prospective observational study, including children who required mechanical ventilation (MV), registered in the multicentre ENVIN-HELICS database from 2014 to 2019. The regression coefficients of each independent risk factor for VAP were used to create the RISVAP score. Each factor scored 0 if it was absent, or, if it was present, an assigned value from 1 to 7, according to the regression coefficient. RESULTS: A total of 3798 patients were included, 97(2.5%) developing VAP. The independent risk factors for VAP were: female (odds ratio [OR]: 1.642, p = 0.024), MV > 4 days (OR: 26.79, p < 0.001), length in pediatric intensive care unit > 7 days (OR: 11.74, p < 0.001), and previous colonisation (OR: 4.18, p < 0.001). The RISVAP was calculated for each patient as the sum of all the independent risk factors. Three risk groups were obtained: low (0-5 points), intermediate (6-12 points), and high risk for VAP (13-16 points). The area under the curve for the final score was 0.905 (95%confidence interval: 0.888-0.923, p < 0.001). CONCLUSIONS: The RISVAP is the first risk score for VAP in pediatric populations. Using this predictive score, might be helpful to detect vulnerable patients and therefore implement preventative strategies.

New multivariable prediction model PEdiatric SEpsis recognition and stratification (PESERS score) shows excellent discriminatory capacity.

AIM: To develop a quantitative predictive scoring model for the early recognition and assessment of paediatric sepsis. METHODS: Prospective observational study including emergency department and in-hospital febrile patients under 18 years. Sepsis diagnose (Goldstein 2005 definitions) was the main outcome. Variables associated with the outcome were included in a multivariable analysis. Cut-off points, odds ratio and coefficients for the variables kept after the multivariable analysis were identified. The score was obtained from the coefficients, The AUC was obtained from ROC-analysis, and internal validation was performed using k-fold cross-validation. RESULTS: The analysis included 210 patients. 45 variables were evaluated and the bivariate analysis identified 24 variables associated with the outcome. After the multivariable regression, 11 variables were kept and the score was obtained. The model yielded an excellent AUC of 0.886 (95% CI 0.845-0.927), p < 0.001 for sepsis recognition. With a cut-off value of 5 for the score, we obtained a sensitivity of 98%, specificity of 76.7%, positive predictive value of 87.9% and negative predictive value of 93.3%. CONCLUSION: The proposed scoring model for paediatric sepsis showed adequate discriminatory capacity and sufficient accuracy, which is of great clinical significance in detecting sepsis early and predicting its severity. Nevertheless external validation is needed before clinical use.

Risk factors and incidence of invasive bacterial infection in severe bronchiolitis: the RICOIB prospective study.

BACKGROUND: Bacterial infection (BI), both community-acquired (CA-BI) and hospital-acquired (HAI), might present as a severe complication in patients with bronchiolitis. This study aimed to describe BI in children with severe bronchiolitis, and to define risk factors for BI. METHODS: This was a prospective, descriptive study that included infants admitted to the pediatric intensive care unit (PICU) due to bronchiolitis between 2011 and 2017. The BROSJOD score was calculated to rate the severity of bronchiolitis. RESULTS: Inclusion of 675 patients, with a median age of 47 days (IQR 25-99). 175 (25.9%) patients developed BI, considered HAI in 36 (20.6%). Patients with BI had higher BROSJOD score, PRISM III, and required invasive mechanical ventilation and inotropic support more frequently (p < 0.001). BI was independently associated with BROSJOD higher than 12 (OR 2.092, 95%CI 1.168-3.748) CA-BI was associated to BROSJOD > 12 (OR 2.435, 95%CI 1.379-4.297) and bacterial co-infection (OR 2.294 95%CI 1.051-5.008). Concerning HAI, an independent association was shown with mechanical ventilation longer than 7 days (OR 5.139 95%CI 1.802-14.652). Infants with BI had longer PICU and hospital stay (p < 0.001), Mortality was higher in patients with HAI. CONCLUSIONS: A quarter of infants with severe bronchiolitis developed BI. A BROSJOD > 12 may alert the presence of CA-BI, especially pneumonia. Patients with BI have higher morbidity and mortality.

Bronchiolitis, epidemiological changes during the SARS-CoV-2 pandemic.

BACKGROUND: Bronchiolitis is the most common viral infection of the lower respiratory tract in infants under 2 years of age. The aim of this study was to analyze and compare the seasonal bronchiolitis peaks before and during the SARS-CoV-2 pandemic. METHODS: Descriptive, prospective, and observational study. Patients with severe bronchiolitis admitted to the Pediatric Intensive Care Unit (PICU) of a referral tertiary hospital between September 2010 and June 2021 were included. Demographic data were collected. Viral laboratory-confirmation was carried out. Each season was analyzed and compared. The daily average temperature was collected. RESULTS: 1116 patients were recruited, 58.2% of them males. The median age was 49 days. Respiratory syncytial virus (RSV) was isolated in 782 cases (70.1%). In April 2021, the first and only case of bronchiolitis caused by SARS-CoV-2 was identified. The pre- and post-pandemic periods were compared. There were statistically significant differences regarding: age, 47 vs. 73 days (p = 0.006), PICU and hospital length of stay (p = 0.024 and p = 0.001, respectively), and etiology (p = 0.031). The peak for bronchiolitis in 2020 was non-existent before week 52. A delayed peak was seen around week 26/2021. The mean temperature during the epidemic peak was 10ºC for the years of the last decade and is 23ºC for the present season. CONCLUSION: The COVID-19 pandemic outbreak has led to a clearly observable epidemiological change regarding acute bronchiolitis, which should be studied in detail. The influence of the environmental temperature does not seem to determine the viral circulation.

Mid-regional pro-adrenomedullin for diagnosing evolution after cardiac surgery in newborns: the PRONEW study.

Newborns are the most vulnerable patients after cardiac surgery. Although mortality risk scores before surgery may help predict the risk of poor outcome, new tools are required, and biomarkers could add objective data to these tools. The aim of this study was to assess the ability of mid-regional pro-adrenomedullin (pro-ADM) and pro-atrial natriuretic peptide (pro-ANP) to predict poor outcome after cardiac surgery. This is a pilot diagnostic accuracy study that includes newborns and infants under 2 months admitted to an intensive care unit after cardiac surgery. Pro-ADM and pro-ANP were determined immediately upon admission. Poor outcome was defined as mortality, cardiac arrest, requiring extracorporeal support, requiring renal replacement therapy, or neurological injury. Forty-four patients were included. Twenty-six (59%) had a STAT category of ≥ 4. Ten patients (22.7%) presented a poor outcome, four of whom (9.1%) died. Pro-ADM was higher in patients with poor outcome (p = 0.024) and death (p = 0.012). Pro-ADM showed the best area under curve (AUC) for predicting poor outcome (0.735) and mortality alone (0.869). A pro-ADM of 2 nmol/L had a Sn of 75% and a Sp of 85% for predicting mortality. Pro-ADM > 2 nmol/L was independently associated with poor outcome (OR 5.8) and mortality (OR 14.1). Although higher pro-ANP values were associated with poor outcomes, no cut-off point were found. The combination of STAT ≥ 4 and the biomarkers did not enhance predictive power for poor outcome or mortality.Conclusion: Pro-ADM and pro-ANP determined immediately after surgery could be helpful for stratifying risk of poor outcome and mortality in newborns. What is Known: • Some congenital heart diseases must be corrected/palliated during the first days of life. A useful tool to predict the risk of severe complications has not been proposed. • Most unstable newborns would have higher values of biomarkers such as pro-ADM and pro-ANP related to shock and compensatory actions. What is New: • Pro-ADM and pro-ANP seem to be good biomarkers to predict poor outcome after cardiac surgery. A pro-ADM < 2 nmol/L would imply a low likelihood of a poor outcome. • Deepening the analysis of biomarkers can help in making decisions to prevent/treat complications.

An algorithm combining procalcitonin and lung ultrasound improves the diagnosis of bacterial pneumonia in critically ill children: The PROLUSP study, a randomized clinical trial.

BACKGROUND: Lung ultrasound (LUS) and procalcitonin (PCT) are independently used to improve accuracy when diagnosing lung infections. The aim of the study was to evaluate the accuracy of a new algorithm combining LUS and PCT for the diagnosis of bacterial pneumonia. METHODS: Randomized, blinded, comparative effectiveness clinical trial. Children <18 years old with suspected pneumonia admitted to pediatric intensive care unit were included, and randomized into experimental group (EG) or control group (CG) if LUS or chest X-Ray (CXR) were done as the first pulmonary image, respectively. PCT was determined. In patients with bacterial pneumonia, sensitivity, specificity, and predictive values of LUS, CXR, and of both combined with PCT were analyzed and compared. Concordance between the final diagnosis and the diagnosis concluded through the imaging test was assessed. RESULTS: A total of 194 children, with a median age of 134 (interquartile range [IQR]: 39-554) days, were enrolled, 96 randomized into the EG and 98 into the CG. Bacterial pneumonia was diagnosed in 97 patients. Sensitivity and specificity for bacterial pneumonia diagnosis were 78% (95% confidence interval [CI]: 70-85) and 98% (95% CI: 93-99) for LUS, 85% (95% CI: 78-90) and 53% (95% CI: 43-62) for CXR, 90% (95% CI: 83-94) and 85% (95% CI: 76-91) when combining LUS and PCT, and 95% (95% CI: 90-98) and 41% (95% CI: 31-52) when combining CXR and PCT. The positive predictive value for LUS and PCT was 88% (95% C:I 79%-93%) versus 68% (95% CI: 60-75) for CXR and PCT. The concordance between the final diagnosis and LUS had a kappa value of 0.69 (95% CI: 0.62-0.75) versus 0.34 (95% CI: 0.21-0.45) for CXR, (p < 0.001). CONCLUSIONS: The combination of LUS and PCT presented a better accuracy for bacterial pneumonia diagnosis than combining CXR and PCT. Therefore, its implementation could be a reliable tool for pneumonia diagnosis in critically ill children.

Low levels of CIITA and high levels of SOCS1 predict COVID-19 disease severity in children and adults.

It is unclear why COVID-19 ranges from asymptomatic to severe. When SARS-CoV-2 is detected, interferon (IFN) response is activated. When it is insufficient or delayed, it might lead to overproduction of cytokines and severe COVID-19. The aim was to compare cytokine and IFN patterns in children and adults with differing severity with SARS-CoV-2.It was a prospective, observational study, including 84 patients. Patients with moderate/severe disease had higher cytokines' values than patients with mild disease (p< 0.001).Two IFN genes were selected to build a decision tree for severity classification: SOCS1 (representative of the rest of the IFN genes) and CIITA (inverse correlation). Low values of CIITA and high values of SOCS1 indicated severe disease. This method correctly classified 33/38(86.8%) of children and 27/34 (79.4%) of adults. To conclude, patients with severe disease had an elevated cytokine pattern, which correlated with the IFN response, with low CIITA and high SOCS1 values.