Publications

2023

Russell, Robert T, Melania M Bembea, Matthew A Borgman, Randall S Burd, Barbara A Gaines, Mubeen Jafri, Cassandra D Josephson, et al. “Pediatric Traumatic Hemorrhagic Shock Consensus Conference Research Priorities.”. The Journal of Trauma and Acute Care Surgery 94, no. 1S Suppl 1 (2023): S11-S18. doi:10.1097/TA.0000000000003802.

BACKGROUND: Traumatic injury is the leading cause of death in children and adolescents. Hemorrhagic shock remains a common and preventable cause of death in the pediatric trauma patients. A paucity of high-quality evidence is available to guide specific aspects of hemorrhage control in this population. We sought to identify high-priority research topics for the care of pediatric trauma patients in hemorrhagic shock.

METHODS: A panel of 16 consensus multidisciplinary committee members from the Pediatric Traumatic Hemorrhagic Shock Consensus Conference developed research priorities for addressing knowledge gaps in the care of injured children and adolescents in hemorrhagic shock. These ideas were informed by a systematic review of topics in this area and a discussion of these areas in the consensus conference. Research priorities were synthesized along themes and prioritized by anonymous voting.

RESULTS: Eleven research priorities that warrant additional investigation were identified by the consensus committee. Areas of proposed study included well-designed clinical trials and evaluations, including increasing the speed and accuracy of identifying and treating hemorrhagic shock, defining the role of whole blood and tranexamic acid use, and assessment of the utility and appropriate use of viscoelastic techniques during early resuscitation. The committee recommended the need to standardize essential definitions, data elements, and data collection to facilitate research in this area.

CONCLUSION: Research gaps remain in many areas related to the care of hemorrhagic shock after pediatric injury. Addressing these gaps is needed to develop improved evidence-based recommendations for the care of pediatric trauma patients in hemorrhagic shock.

Yazer, Mark H, José R Díaz-Valdés, Darrell J Triulzi, Philip C Spinella, Stephen P Emery, Pampee P Young, Jansen N Seheult, Christine M Leeper, Jennifer M Jones, and Andrew P Cap. “Considering Equality in Transfusion Medicine Practice.”. British Journal of Haematology 201, no. 6 (2023): 1245-47. doi:10.1111/bjh.18830.
Halasa, Natasha B, Andrew J Spieker, Cameron C Young, Samantha M Olson, Margaret M Newhams, Justin Z Amarin, Kristin L Moffitt, et al. “Life-Threatening Complications of Influenza Vs Coronavirus Disease 2019 (COVID-19) in US Children.”. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America 76, no. 3 (2023): e280-e290. doi:10.1093/cid/ciac477.

BACKGROUND: Clinical differences between critical illness from influenza infection vs coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients.

METHODS: We compared demographics, clinical characteristics, and outcomes of US children (aged 8 months to 17 years) admitted to the intensive care or high-acuity unit with influenza or COVID-19. Using mixed-effects models, we assessed the odds of death or requiring life support for influenza vs COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity.

RESULTS: Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median, 5.2 years vs 13.8 years), less likely to be non-Hispanic Black (14.5% vs 27.6%) or Hispanic (24.0% vs 36.2%), and less likely to have ≥1 underlying condition (66.4% vs 78.5%) or be obese (21.4% vs 42.2%), and a shorter hospital stay (median, 5 days vs 7 days). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life support in children with influenza vs COVID-19 were similar (adjusted odds ratio, 1.30; 95% confidence interval, .78-2.15; P = .32).

CONCLUSIONS: Despite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19.

Benamar, Mehdi, Qian Chen, Janet Chou, Amélie M Julé, Rafik Boudra, Paola Contini, Elena Crestani, et al. “The Notch1/CD22 Signaling Axis Disrupts Treg Function in SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children.”. The Journal of Clinical Investigation 133, no. 1 (2023). doi:10.1172/JCI163235.

Multisystem inflammatory syndrome in children (MIS-C) evolves in some pediatric patients following acute infection with SARS-CoV-2 by hitherto unknown mechanisms. Whereas acute-COVID-19 severity and outcomes were previously correlated with Notch4 expression on Tregs, here, we show that Tregs in MIS-C were destabilized through a Notch1-dependent mechanism. Genetic analysis revealed that patients with MIS-C had enrichment of rare deleterious variants affecting inflammation and autoimmunity pathways, including dominant-negative mutations in the Notch1 regulators NUMB and NUMBL leading to Notch1 upregulation. Notch1 signaling in Tregs induced CD22, leading to their destabilization in a mTORC1-dependent manner and to the promotion of systemic inflammation. These results identify a Notch1/CD22 signaling axis that disrupts Treg function in MIS-C and point to distinct immune checkpoints controlled by individual Treg Notch receptors that shape the inflammatory outcome in SARS-CoV-2 infection.

Russell, Robert T, Christine M Leeper, and Philip C Spinella. “Damage-Control Resuscitation in Pediatric Trauma: What You Need to Know.”. The Journal of Trauma and Acute Care Surgery 95, no. 4 (2023): 472-80. doi:10.1097/TA.0000000000004081.

Damage-control resuscitation (DCR) consists of rapid control of bleeding, avoidance of hemodilution, acidosis, and hypothermia; early empiric balanced transfusions with red blood cells, plasma and platelets, or whole blood when available, and the use of intravenous or mechanical hemostatic adjuncts when indicated. The principles used in pediatric and adult trauma patients are quite similar. There are very important recognized physiologic differences in children with traumatic hemorrhagic shock that warrant slight variations in DCR. In pediatric trauma patients, early physiologic signs of shock may be different from adults and the early recognition of this is critical to enable prompt resuscitation and utilization of damage control principles. This review details the current principles of pediatric DCR based on the best available literature, expert consensus recommendations, and also describes a practical guide for implementation of DCR strategies for pediatric trauma patients.

Russell, Robert T, Joseph R Esparaz, Michael A Beckwith, Peter J Abraham, Melania M Bembea, Matthew A Borgman, Randall S Burd, et al. “Pediatric Traumatic Hemorrhagic Shock Consensus Conference Recommendations.”. The Journal of Trauma and Acute Care Surgery 94, no. 1S Suppl 1 (2023): S2-S10. doi:10.1097/TA.0000000000003805.

Hemorrhagic shock in pediatric trauma patients remains a challenging yet preventable cause of death. There is little high-quality evidence available to guide specific aspects of hemorrhage control and specific resuscitation practices in this population. We sought to generate clinical recommendations, expert consensus, and good practice statements to aid providers in care for these difficult patients.The Pediatric Traumatic Hemorrhagic Shock Consensus Conference process included systematic reviews related to six subtopics and one consensus meeting. A panel of 16 consensus multidisciplinary committee members evaluated the literature related to 6 specific topics: (1) blood products and fluid resuscitation for hemostatic resuscitation, (2) utilization of prehospital blood products, (3) use of hemostatic adjuncts, (4) tourniquet use, (5) prehospital airway and blood pressure management, and (6) conventional coagulation tests or thromboelastography-guided resuscitation. A total of 21 recommendations are detailed in this article: 2 clinical recommendations, 14 expert consensus statements, and 5 good practice statements. The statement, the panel's voting outcome, and the rationale for each statement intend to give pediatric trauma providers the latest evidence and guidance to care for pediatric trauma patients experiencing hemorrhagic shock. With a broad multidisciplinary representation, the Pediatric Traumatic Hemorrhagic Shock Consensus Conference systematically evaluated the literature and developed clinical recommendations, expert consensus, and good practice statements concerning topics in traumatically injured pediatric patients with hemorrhagic shock.