Results from preclinical studies suggest that age-dependent differences in host defense and the pulmonary renin–angiotensin system (RAS) are responsible for observed differences in epidemiology of acute respiratory distress syndrome (ARDS) between children and adults. The present study compares biomarkers of host defense and RAS in bronchoalveolar lavage (BAL) fluid from neonates, children, adults, and older adults with ARDS. In this prospective observational study, we enrolled mechanical ventilated ARDS patients categorized into four age groups: 20 neonates (< 28 days corrected postnatal age), 29 children (28 days–18 years), 26 adults (18–65 years), and 17 older adults (> 65 years of age). All patients underwent a nondirected BAL within 72 h after intubation. Activities of the two main enzymes of RAS, angiotensin converting enzyme (ACE) and ACE2, and levels of biomarkers of inflammation, endothelial activation, and epithelial damage were determined in BAL fluid. Levels of myeloperoxidase, interleukin (IL)-6, IL-10, and p-selectin were higher with increasing age, whereas intercellular adhesion molecule-1 was higher in neonates. No differences in activity of ACE and ACE2 were seen between the four age groups. Age-dependent differences in the levels of biomarkers in lungs of ARDS patients are present. Especially, higher levels of markers involved in the neutrophil response were found with increasing age. In contrast to preclinical studies, age is not associated with changes in the pulmonary RAS.

Outcomes for children diagnosed with cancer have improved dramatically over the past 20 years. However, although 40% of pediatric cancer patients require at least one intensive care admission throughout their disease course, PICU outcomes and resource utilization by this population have not been rigorously studied in this specific group. Using a systematic strategy, we searched Medline, Embase, and CINAHL databases for articles describing PICU mortality of pediatric cancer patients admitted to PICU. Two investigators independently applied eligibility criteria, assessed data quality, and extracted data. We pooled PICU mortality estimates using random-effects models and examined mortality trends over time using meta-regression models. Out of 1218 identified manuscripts, 31 studies were included covering 16,853 PICU admissions with the majority being retrospective in nature. Overall pooled weighted mortality was 27.8% (95% confidence interval (CI), 23.7-31.9%). Mortality decreased slightly over time when post-operative patients were excluded. The use of mechanical ventilation (odds ratio (OR): 18.49 [95% CI 13.79-24.78], p < 0.001), inotropic support (OR: 14.05 [95% CI 9.16-21.57], p < 0.001), or continuous renal replacement therapy (OR: 3.24 [95% CI 1.31-8.04], p = 0.01) was significantly associated with PICU mortality. PICU mortality rates of pediatric cancer patients are far higher when compared to current mortality rates of the general PICU population. PICU mortality has remained relatively unchanged over the past decades, a slight decrease was only seen when post-operative patients were excluded. This compared infavorably with the improved mortality seen in adults with cancer admitted to ICU, where research-led improvements have led to the paradigm of unlimited, aggressive ICU management without any limitations on resuscitations status, for a time-limited trial.

Objectives: The Pediatric Sepsis Definition Task Force developed and validated a new organ dysfunction score, the Phoenix Sepsis Score (PSS), as a predictor of mortality in children with suspected or confirmed infection. The PSS showed improved performance compared with prior scores. However, the criteria were derived in a general pediatric population, in which only 10% had cancer. Given that pediatric cancer patients with sepsis have higher mortality compared with noncancer patients with sepsis, we aimed to assess the PSS in PICU patients with cancer and sepsis. Design: Retrospective multicenter cohort study. Setting: Twelve PICUs across Europe. Patients: Each PICU identified patients 18 years young or younger, with underlying malignancy and suspected or proven sepsis, and admission between January 1, 2018, and January 1, 2020. Interventions: None. Measurements and Main Results: The PSS and three other scores, including Phoenix-8, Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score, and pediatric Sequential Organ Failure Assessment (pSOFA) score, were calculated for comparison. The primary outcome was 90-day all-cause mortality. We compared score performance using area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC) analyses. Among 383 patients with proven or suspected sepsis, 90-day mortality was 19.3% (74/383). We failed to identify an association between a particular score and performance for 90-day mortality. The mean (95% CI) values for the AUROC of each score was: PSS 0.66 (0.59–0.72), Phoenix-8 0.65 (0.58–0.72), PELOD-2 0.64 (0.57–0.71), and pSOFA 0.67 (0.60–0.74) and for the AUPRC of each score: PSS 0.32 (0.23–0.42), Phoenix-8 0.32 (0.23–0.42), PELOD-2 0.32 (0.22–0.43), and pSOFA 0.36 (0.26–0.46). Similar results were obtained for PICU mortality or sepsis-related PICU mortality. Conclusions: Contrary to the general PICU population, our retrospective test of the PSS in a PICU oncology dataset with suspected or proved sepsis from European PICUs, 2018–2020, failed to identify improved performance in association with mortality. This unique patient population deserves development of organ dysfunction scores that reflect organ dysfunction and mortality data specifically from these patients and will require prospective validation in future studies.

Introduction: Spirometry plays an important role in the assessment of possible respiratory failure in children with neuromuscular diseases (NMDs). However, obtaining reliable spirometry results is a major challenge. We studied the relation between oscillometry and spirometry results. Oscillometry is an easy, noninvasive method to measure respiratory resistance R and reactance X. We hypothesized an increased R and reduced X in patients with more reduced lung function.Methods: In this prospective single‐center study, we included all children with NMDs able to perform spirometry. We consecutively measured R and X at 5, 11, and 19 Hz and (forced) vital capacity, peak expiratory flow. Spearman correlation coefficients and positive and negative predictive values were calculated. Regression curves were estimated.Results: We included 148 patients, median age 13 years (interquartile range: 8–16). A negative correlation was found between R and spirometry outcomes (Spearman correlation coefficient [ρ]: −0.5 to −0.6, p < 0.001). A positive correlation was found between X (i.e., less negative outcomes) and spirometry outcomes (ρ: 0.4–0.6, p < 0.001). Highest correlation was found at lower frequencies. Regression analysis showed a nonlinear relation. Measurement of inspiratory and expiratory R and X did not provide added value. Positive predictive values of 80%–85% were found for z‐scores of R measured at 5 Hz versus (F)VC ≤ 60%.Conclusion: We found a nonlinear relation between oscillometry and spirometry results with increased R and reduced X in patients with more restrictive lung function decline. Given the difficulties with performing spirometry, oscillometry may be a promising substitute.

The use of extracorporeal membrane oxygenation (ECMO) in pediatric patients with underlying malignancies remains controversial. However, in an era in which the survival rates for children with malignancies have increased significantly and several recent reports have demonstrated effective ECMO use in children with cancer, we aimed to estimate the outcome and complications of ECMO treatment in these children. We searched MEDLINE, Embase and CINAHL databases for studies on the use ECMO in pediatric patients with an underlying malignancy from inception to September 2020. This review was conducted in adherence to Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Study eligibility was independently assessed by two authors and disagreements resolved by a third author. Included studies were evaluated for quality using the Newcastle–Ottawa Scale (NOS). Random effects meta-analyses (DerSimonian and Laird) were performed. The primary outcomes were mortality during ECMO or hospital mortality. Thirteen retrospective, observational cohort studies were included, most of moderate quality (625 patients). The commonest indication for ECMO was severe respiratory failure (92%). Pooled mortality during ECMO was 55% (95% confidence interval [CI], 47–63%) and pooled hospital mortality was 60% (95% CI 54–67%). Although heterogeneity among the included studies was low, confidence intervals were large. In addition, the majority of the data were derived from registries with overlapping patients which were excluded for the meta-analyses to prevent resampling of the same participants across the included studies. Finally, there was a lack of consistent complications reporting among the studies. Significantly higher mortalities than in general PICU patients was reported with the use of ECMO in children with malignancies. Although these results need to be interpreted with caution due to the lack of granular data, they suggest that ECMO appears to represents a viable rescue option for selected patients with underlying malignancies. There is an urgent need for additional data to define patients for whom ECMO may provide benefit or harm.