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Introduction: Retrospective data suggest that pediatric hematopoietic cell transplant (HCT) patients placed on non-invasive ventilation (NIV) prior to intubation have increased risk of mortality compared to patients who are intubated earlier in their course. The HCT-CI subgroup of the PALISI Network set out to gain a better understanding of factors that influence clinician's decisions surrounding timing of intubation of pediatric HCT patients., Methods: We validated and distributed a brief survey exploring potential factors that may influence clinician's decisions around timing of intubation of pediatric HCT patients with acute lung injury (ALI)., Results: One hundred and four of the 869 PALISI Network's members responded to the survey; 97 of these respondents acknowledged caring for HCT patients and were offered the remainder of the survey. The majority of respondents were PICU physicians (96%), with a small number of Advanced Practice Providers and HCT physicians. As expected, poor prognosis categories were perceived as a factors that delay timing to intubation whereas need for invasive procedures was perceived as a factor shortening timing to intubation. Concerns for oxygen toxicity or NIV-associated lung injury were not believed to influence timing of intubation., Discussion: Our survey indicates increased risk of ALI from prolonged NIV and oxygen toxicity in HCT patients are not a concern for most clinicians. Further education of pediatric ICU clinicians around these risk factors could lead to improvement in outcomes and demands further study. Additionally, clinicians identified concerns for the patient's poor prognosis as a common reason for delayed intubation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hume, Goertzen, Avent, Steiner, McArthur and the Hematopoietic Cell Transplant and Cancer Immunotherapy subgroup of the Pediatric Acute Lung Injury and Sepsis Investigator’s Network (HCT-CI subgroup of PALISI).)

Introduction: Diffuse alveolar hemorrhage (DAH) is a devastating disease process with 50-100% mortality in oncology and hematopoietic cell transplant (HCT) recipients. High concentrations of tissue factors have been demonstrated in the alveolar wall in acute respiratory distress syndrome and DAH, along with elevated levels of tissue factor pathway inhibitors. Activated recombinant factor VII (rFVIIa) activates the tissue factor pathway, successfully overcoming the tissue factor pathway inhibitor (TFPI) inhibition of activation of Factor X. Intrapulmonary administration (IP) of rFVIIa in DAH is described in small case series with successful hemostasis and minimal complications., Methods: We completed a single center retrospective descriptive study of treatment with rFVIIa and outcomes in pediatric oncology and HCT patients with pulmonary hemorrhage at a quaternary hematology/oncology hospital between 2011 and 2019. We aimed to assess the safety and survival of patients with pulmonary hemorrhage who received of IP rFVIIa., Results: We identified 31 patients with pulmonary hemorrhage requiring ICU care. Thirteen patients received intrapulmonary rFVIIa, while eighteen patients did not. Overall, 13 of 31 patients (41.9%) survived ICU discharge. ICU survival (n=6) amongst those in the IP rFVIIa group was 46.2% compared to 38.9% (n=7) in those who did not receive IP therapy (p=0.69). Hospital survival was 46.2% in the IP group and 27.8% in the non-IP group (p=0.45). There were no adverse events noted from use of IP FVIIa., Conclusions: Intrapulmonary rFVIIa can be safely administered in pediatric oncology patients with pulmonary hemorrhage and should be considered a viable treatment option for these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hurley, McArthur, Gossett, Hall, Barker, Hijano, Hines, Kang, Rains, Srinivasan, Suliman, Qudeimat and Ghafoor.)

Background: High-quality clinical care requires excellent interdisciplinary communication, especially during emergencies, and no tools exist to evaluate communication in critical care. We describe the development of a pragmatic tool focusing on interdisciplinary communication during patient deterioration (CritCom)., Methods: The preliminary CritCom tool was developed after a literature review and consultation with a multidisciplinary panel of global experts in communication, pediatric oncology, and critical care to review the domains and establish content validity iteratively. Face and linguistic validity were established through cognitive interviews, translation, and linguistic synthesis. We conducted a pilot study among an international group of clinicians to establish reliability and usability., Results: After reviewing 105 potential survey items, we identified 52 items across seven domains. These were refined through cognitive interviews with 36 clinicians from 15 countries. CritCom was piloted with 433 clinicians (58% nurses, 36% physicians, and 6% other) from 42 hospitals in 22 countries. Psychometric testing guided the refinement of the items for the final tool. CritCom comprised six domains with five items each (30 total). The final tool has excellent reliability (Cronbach's alpha 0.81-0.86), usability (93% agree or strongly agree that the tool is easy to use), and similar performance between English and Spanish tools. Confirmatory factor analysis was used to establish the final 6-domain structure., Conclusions: CritCom is a reliable and pragmatic bilingual tool to assess the quality of interdisciplinary communication around patient deterioration for children in diverse resource levels globally. Critcom results can be used to design and evaluate interventions to improve team communication., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rivera, Malone, Puerto-Torres, Prewitt, Counts, Wiphatphumiprates, Sakaan, Al Zebin, Arias, Bhattacharyya, Gunasekera, Johnson, Kambugu, Kaye, Mandrell, Mack, McArthur, Mendez, Morrissey, Sharara-Chami, Snaman, Sniderman, Luke, Graetz and Agulnik.)

Introduction: Children with cancer have a higher risk of adverse outcomes during critical illness than general pediatric populations. In Low- and middle-income countries, lack of resources can further negatively impact outcomes in critically ill children with cancer., Methods: In this study, we describe the outcomes of a large cohort of children with cancer including mortality and resource utilization. We performed a retrospective review of all patients admitted to our PICU between December 12th, 2013 and December 31st, 2019. Outcomes were defined as recovery or death and resource utilization was described via use of critical care interventions, Length of stay as well as PICU- and Mechanical Ventilation- free days., Results: Overall mortality was 6.9% while mortality in the unplanned admissions was 9.1%. This remained lower than expected mortality based on PIM2 scoring. Type of PICU admission, Neurological Deterioration as a cause of PICU admission, and PIM2 were significant as risk factors in univariate analysis, but only PIM2 remained significant in the multivariate analysis., Discussion: Our Study shows that high survival rates are achievable for children with cancer with critical illness in resource-limited settings with provision of high-quality critical care. Organizational and clinical practice facilitating quality improvement and early identification and management of critical illness may attenuate the impact of known risk factors for mortality in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cardenas-Aguirre, Hernandez-Garcia, Lira-De-Leon, Munoz-Brugal, Wang, Villanueva-Diaz, Ruiz-Perez, Mijares-Tobias, Giles-Gonzalez, McArthur, Escamilla-Aisan, Arias, Devidas and Agulnik.)

Introduction: Pediatric patients who undergo hematopoietic cell transplant (HCT) or chimeric antigen receptor T-cell (CAR-T) therapy are at high risk for complications leading to organ failure and the need for critical care resources. Extracorporeal membrane oxygenation (ECMO) is a supportive modality that is used for cardiac and respiratory failure refractory to conventional therapies. While the use of ECMO is increasing for patients who receive HCT, candidacy for these patients remains controversial. We therefore surveyed pediatric critical care and HCT providers across North America and Europe to evaluate current provider opinions and decision-making and institutional practices regarding ECMO use for patients treated with HCT or CAR-T., Methods: An electronic twenty-eight question survey was distributed to pediatric critical care and HCT providers practicing in North America (United States and Canada) and Europe through the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network and individual emails. Responses to the survey were recorded in a REDCap ® database., Results: Two-hundred and ten participants completed the survey. Of these, 159 (76%) identified themselves as pediatric critical care physicians and 47 (22%) as pediatric HCT physicians or oncologists. The majority (99.5%) of survey respondents stated that they would consider patients treated with HCT or CAR-T therapy as candidates for ECMO support. However, pediatric critical care physicians identified more absolute and relative contraindications for ECMO than non-pediatric critical care physicians. While only 0.5% of respondents reported that they consider HCT as an absolute contraindication for ECMO, 6% of respondents stated that ECMO is contraindicated in HCT patients within their institution and only 23% have an institutional protocol or policy to guide the evaluation for ECMO candidacy of these patients. Almost half (49.1%) of respondents would accept a survival to hospital discharge of 20-30% for pediatric HCT patients requiring ECMO as adequate., Conclusions: ECMO use for pediatric patients treated with HCT and CAR-T therapy is generally acceptable amongst physicians. However, there are differences in the evaluation and decision-making regarding ECMO candidacy amongst providers across medical specialties and institutions. Therefore, multidisciplinary collaboration is an essential component in establishing practice guidelines and advancing ECMO outcomes for these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer NJS declared a shared affiliation with one of the authors JM, to the handling editor at the time of review., (Copyright © 2021 Ghafoor, Fan, Di Nardo, Talleur, Saini, Potera, Lehmann, Annich, Wang, McArthur, Sandhu and the Pediatric Acute Lung Injury and Sepsis Investigator (PALISI) Network.)

Pulmonary complications are common in children following hematopoietic cell transplantation (HCT) and contribute to their morbidity and mortality. Early diagnosis is essential for management and prevention of progression of lung injury and damage. In many cases, diagnosis can be challenging and may require diagnostic imaging and more invasive testing such as bronchoscopy and lung biopsy. We report the case of a 12-year-old girl who developed recurrent episodes of acute respiratory failure requiring intensive care unit admission in the post-HCT phase and describe the diagnostic and multidisciplinary approach for her management. In addition, we review the diagnostic approach of pulmonary complications post-HCT and highlight the utility and risks of bronchoscopy and lung biopsy in these children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Elbahlawan, McArthur, Morin, Abdelhafeez, McCarville, Ruiz, Srinivasan and Qudeimat.)

Introduction: Delirium occurs frequently in adults undergoing hematopoietic cell transplantation, with significant associated morbidity. Little is known about the burden of delirium in children in the peri-transplant period. This study was designed to determine delirium rates, define risk factors (demographic and treatment related), and establish feasibility of multi-institutional bedside screening for delirium in children undergoing hematopoietic cell transplant. Methods: This is a multi-institutional point prevalence study. All subjects were prospectively screened for delirium twice daily using the Cornell Assessment of Pediatric Delirium over a 10-day period. De-identified data, including basic demographics and daily characteristics, were extracted from the electronic medical record. Results: Eleven North American institutions were included, 106 children were enrolled, and 883 hospital days were captured. Delirium screening was successfully completed on more than 98% of the study days. Forty-eight children (45%) developed delirium over the course of the 10-day study. Children were diagnosed with delirium on 161/883 study days, for an overall delirium rate of 18% per day. Higher delirium rates were noted in children <5 years old (aOR 0.41 for children over 5 years), and in association with specific medications (melatonin, steroids, and tacrolimus). Conclusion: Delirium was a frequent occurrence in our study cohort, with identifiable risk factors. Delirium screening is highly feasible in the pediatric hematopoietic cell transplant patient population. A large-scale prospective longitudinal study following children throughout their transplant course is urgently needed to fully describe the epidemiology of pediatric delirium, explore the effects of delirium on patient outcomes, and establish guidelines to prevent and treat delirium in the peri-transplant period., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Traube, Gerber, Mauer, Small, Broglie, Chopra, Duncan, Ebens, Fitzgerald, Freedman, Hudspeth, Hurley, Mahadeo, McArthur, Shapiro, Sharron, Wall, Zinter, Greenwald, Silver and Boulad.)

Pulmonary complications are common following hematopoietic cell transplantation (HCT) and contribute significantly to its morbidity and mortality. Diffuse alveolar hemorrhage is a devastating non-infectious complication that occurs in up to 5% of patients post-HCT. Historically, it carries a high mortality burden of 60-100%. The etiology remains ill-defined but is thought to be due to lung injury from conditioning regimens, total body irradiation, occult infections, and other comorbidities such as graft vs. host disease, thrombotic microangiopathy, and subsequent cytokine release and inflammation. Clinically, patients present with hypoxemia, dyspnea, and diffuse opacities consistent with an alveolar disease process on chest radiography. Diagnosis is most commonly confirmed with bronchoscopy findings of progressively bloodier bronchoalveolar lavage or the presence of hemosiderin-laden macrophages on microscopy. Treatment with glucocorticoids is common though dosing and duration of therapy remains variable. Other agents, such as aminocaproic acid, tranexamic acid, and activated recombinant factor VIIa have also been tried with mixed results. We present a review of diffuse alveolar hemorrhage with a focus on its pathogenesis and treatment options., (Copyright © 2020 Fan, McArthur, Morrison and Ghafoor.)