Clinical Focus


  • Pediatric Critical Care Medicine
  • Neurocritical Care

Academic Appointments


Administrative Appointments


  • Director Pediatric Neurocritical care, Critical Care Medicine (2018 - Present)
  • Associate Medical Director, Pediatric Intensive Care Unit (2020 - Present)
  • Advising APD, Advising APD, Combined Pediatric-Anesthesiology Residency (2023 - Present)

Boards, Advisory Committees, Professional Organizations


  • Appointed Committee Member, Post Graduate and Fellowship Education Committee, Society of Critical Care Medicine (SCCM) (2017 - 2020)
  • Co-Chair, Brain & Behavior Quality Assurance and Performance Improvement Committee (2019 - Present)
  • Co-Chair, Professional Practice Evaluation Committee. Lucile Packard Children’s Hospital, Stanford University (2018 - Present)
  • Member, Society of Critical Care Medicine (SCCM) (2013 - Present)
  • Member, Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) (2016 - Present)
  • Member, Pediatric Neurocritical Care Research Group (PNCRG) (2016 - Present)
  • Member, Neurocritical Care Society (NCS) Pediatric Neurocritical Care Section (2018 - Present)
  • Member, Council on Child Abuse and Neglect (COCAN), American Academy of Pediatrics (2019 - Present)
  • Fellow, American Academy of Pediatrics (2017 - Present)

Professional Education


  • Medical Education: Medical College Of Wisconsin (2010) WI
  • Board Certification: American Board of Pediatrics, Pediatric Critical Care Medicine (2016)
  • Fellowship: Johns Hopkins University School of Medicine (2016) MD
  • Board Certification: American Board of Pediatrics, Pediatrics (2013)
  • Residency: Children's National Medical Center (2013) DC

Current Research and Scholarly Interests


My research interests reside in the field of Neurocritical Care Medicine. My research focus has included inflammation following traumatic brain injury, outcome prediction after cardiac arrest, and neuro-monitoring in the pediatric intensive care setting. These interests are integrated clinically to focus on the merging of specialized neurologic monitoring and care with prognostic efforts in critically ill patients.

Clinical Trials


  • GD2 CAR T Cells in Diffuse Intrinsic Pontine Gliomas(DIPG) & Spinal Diffuse Midline Glioma(DMG) Recruiting

    The primary purpose of this study is to test whether GD2-CAR T cells can be successfully made from immune cells collected from children and young adults with H3K27M-mutant diffuse intrinsic pontine glioma (DIPG) or spinal H3K27M-mutant diffuse midline glioma (DMG). H3K27Mmutant testing will occur as part of standard of care prior to enrollment.

    View full details

All Publications


  • High Variability in the Duration of Chest Compression Interruption is Associated With Poor Outcomes in Pediatric Extracorporeal Cardiopulmonary Resuscitation. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Han, P., Rasmussen, L., Su, F., Dacre, M., Knight, L., Berg, M., Tawfik, D., Haileselassie, B. 2024

    Abstract

    To determine the association between chest compression interruption (CCI) patterns and outcomes in pediatric patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR).Cardiopulmonary resuscitation (CPR) data were collected using defibrillator-electrode and bedside monitor waveforms from pediatric ECPR cases between 2013 and 2021. Duration and variability of CCI during cannulation for ECPR was determined and compared with survival to discharge using Fishers exact test and logistic regressions with cluster-robust ses for adjusted analyses.Quaternary care children's hospital.Pediatric patients undergoing ECPR.None.Of 41 ECPR events, median age was 0.7 years (Q1, Q3: 0.1, 5.4), 37% (15/41) survived to hospital discharge with 73% (11/15) of survivors having a favorable neurologic outcome. Median duration of CPR from start of ECPR cannulation procedure to initiation of extracorporeal membrane oxygenation (ECMO) flow was 21 minutes (18, 30). Median duration of no-flow times associated with CCI during ECMO cannulation was 11 seconds (5, 28). Following planned adjustment for known confounders, survival to discharge was inversely associated with maximum duration of CCI (odds ratio [OR] 0.91 [0.86-0.95], p = 0.04) as well as the variability in the CCI duration (OR 0.96 [0.93-0.99], p = 0.04). Cases with both above-average CCI duration and higher CCI variability (sd> 30 s) were associated with lowest survival (12% vs. 54%, p = 0.009). Interaction modeling suggests that lower variability in CCI is associated with improved survival, especially in cases where average CCI durations are higher.Shorter duration of CCI and lower variability in CCI during cannulation for ECPR were associated with survival following refractory pediatric cardiac arrest.

    View details for DOI 10.1097/PCC.0000000000003461

    View details for PubMedID 38299932

  • Knowledge and Practice Gaps in Pediatric Neurocritical Care Nursing: Lessons Learned From a Specialized Educational Boot Camp. Critical care explorations Chang, N., Sperber, A., Casazza, M., Ciraulo, L., Teeyagura, P., Rasmussen, L. 2023; 5 (12): e1018

    Abstract

    OBJECTIVES: Pediatric neurocritical care (PNCC) is a quickly growing subspecialty within pediatric critical care medicine. Standards for care, education, and application of neuromonitoring technologies in PNCC are still being developed. We sought to identify and improve knowledge deficits in neurocritical care with an educational boot camp for nurses.SETTING: Quaternary children's hospital with 36 PICU beds.DESIGN: Preinterventional and postinterventional study.METHODS: A 2-day boot camp course covering neurologic and neurosurgical topics pertinent to PNCC was provided to 46 pediatric acute and critical care nurses divided into three cohorts over 3 years. Participant characteristics were collected, and precourse and postcourse knowledge assessments were administered.RESULTS: Regarding participant characteristics, neither critical care registered nurse certification nor years of nursing experience were associated with better precourse baseline knowledge. Knowledge gaps spanned bedside neurologic assessments, physiologic goals in brain injury, and side effects of neurocritical care medications. In postcourse assessments, all participants showed improvement in scores, and most participants sustained improvements after 6 months. Nurses reported significant improvement in self-reported confidence in caring for the PNCC population. We also observed shorter ICU lengths of stay, decreased hospital incident reports, and decreased time to stroke imaging, although these programmatic metrics cannot be credited to nursing education alone.CONCLUSIONS: PNCC programs should include nursing expertise in the field. However, topics specific to PNCC may not be adequately addressed by existing general critical care nursing education and certification. A multimodal educational boot camp can be an effective method to improve nursing knowledge in PNCC. Our results demonstrate that specialty nursing education in PNCC is both innovative and feasible, with the potential to improve patient care. Further research is needed to determine the benefits of specialty education on quality of care and clinical outcomes.

    View details for DOI 10.1097/CCE.0000000000001018

    View details for PubMedID 38073667

  • Pediatric Moyamoya Revascularization Perioperative Care: A Modified Delphi Study. Neurocritical care Sun, L. R., Jordan, L. C., Smith, E. R., Aldana, P. R., Kirschen, M. P., Guilliams, K., Gupta, N., Steinberg, G. K., Fox, C., Harrar, D. B., Lee, S., Chung, M. G., Dirks, P., Dlamini, N., Maher, C. O., Lehman, L. L., Hong, S. J., Strahle, J. M., Pineda, J. A., Beslow, L. A., Rasmussen, L., Mailo, J., Piatt, J., Lang, S. S., Adelson, P. D., Dewan, M. C., Mineyko, A., McClugage, S., Vadivelu, S., Dowling, M. M., Hersh, D. S. 2023

    Abstract

    Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities.Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement.Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4 h before and 24 h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24 h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24 h, hourly neurologic assessments for at least 12 h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery.In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia.

    View details for DOI 10.1007/s12028-023-01788-0

    View details for PubMedID 37470933

    View details for PubMedCentralID 5443666

  • Performance of a Provider-Assigned Functional Outcome Score in Critically Ill Children. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Wilson, N. E., Su, F., DaCar, A., Chang, N., Kapphahn, K., Schroeder, A. R., Tawfik, D. S., Knight, L., Rasmussen, L. 2023

    Abstract

    OBJECTIVES: Determine agreement between Pediatric Cerebral Performance Category (PCPC) scores integrated into clinical workflow and traditional investigator-assigned scores.DESIGN: Longitudinal study.SETTING: A single-center quaternary-care academic institution.SUBJECTS: Children admitted to the PICU between November 2019 and April 2020.INTERVENTIONS: Providers assigned PCPC scores as part of daily workflow. Investigators assigned scores using retrospective chart review.MEASUREMENTS AND MAIN RESULT: s: Of 803 patients admitted to the PICU, 782 survived and were included. Admission and discharge scores were recorded in 95% and 90% of patients, respectively. Agreement between provider- and investigator-assigned scores was excellent, with a weighted kappa of 0.87 (95% CI, 0.84-0.90) and 0.80 (95% CI, 0.76-0.84) for admission and discharge.CONCLUSIONS: Provider-assigned PCPC scores, documented as standard of care, are largely concordant with retrospective investigator-assigned scores. Measurement of cognitive functional status can be successfully integrated into daily provider workflow for use in the clinical, quality improvement, and research arenas.

    View details for DOI 10.1097/PCC.0000000000003234

    View details for PubMedID 37098780

  • Novel serum biomarkers associated with pediatric hepatic encephalopathy: A systematic review. Journal of pediatric gastroenterology and nutrition Krishnan, K., Rao, M., Chang, N., Casazza, M., Rasmussen, L. K. 2023

    Abstract

    The pathophysiology of pediatric hepatic encephalopathy (HE) is not well understood. Various serum biomarkers associated with HE may provide insight into its pathology, but their use and interpretation in clinical practice for diagnosis and prognostication remain undetermined. We sought to investigate reported correlations of serum biomarkers with presence and degree of HE in children.We conducted a systematic review of studies examining novel serum biomarkers and cytokines in association with HE that included children on PubMed, Embase, Lilacs, and Scopus. We utilized Covidence for abstract and text review by two independent reviewers for each study.We reviewed 2,824 unique publications; 15 met criteria for inclusion. Categories of biomarkers reported were inflammatory cytokines, products of amino acid metabolism, trace elements and vitamins, and hepatic and neuro biomarkers. Of 19 individual biomarkers, only five were measured in more than one study. Elevations in interleukin-6 (IL-6) and tumor necrosis factor- alpha (TNF-alpha) were most commonly reported as associated with HE. Notably, we observed lower average IL-6 and TNF-alpha levels in pediatric-only studies compared to mixed age studies. Overall, high bias and poor applicability to our review question was observed. We encountered low numbers of studies with pediatric focus, and few conducted with low bias study designs.Investigated biomarkers span a large range of categories and suggest potentially useful correlations with HE. Further well-designed prospective biomarker research is necessary to better elucidate the pathogenesis of HE in children and improve early detection and clinical care.

    View details for DOI 10.1097/MPG.0000000000003801

    View details for PubMedID 37084331

  • Proceedings of the First Pediatric Coma and Disorders of Consciousness Symposium by the Curing Coma Campaign, Pediatric Neurocritical Care Research Group, and NINDS: Gearing for Success in Coma Advancements for Children and Neonates. Neurocritical care Boerwinkle, V. L., Schor, N. F., Slomine, B. S., Molteni, E., Ramirez, J., Rasmussen, L., Wyckoff, S. N., Gonzalez, M. J., Gillette, K., Schober, M. E., Wainwright, M., Suarez, J. I. 2023

    Abstract

    This proceedings article presents the scope of pediatric coma and disorders of consciousness based on presentations and discussions at the First Pediatric Disorders of Consciousness Care and Research symposium held on September 14th, 2021. Herein we review the current state of pediatric coma care and research opportunities as well as shared experiences from seasoned researchers and clinicians. Salient current challenges and opportunities in pediatric and neonatal coma care and research were identified through the contributions of the presenters, who were Jose I. Suarez, MD, Nina F. Schor, MD, PhD, Beth S. Slomine, PhD Erika Molteni, PhD, and Jan-Marino Ramirez, PhD, and moderated by Varina L. Boerwinkle, MD, with overview by Mark Wainwright, MD, and subsequent audience discussion. The program, executively planned by Varina L. Boerwinkle, MD, Mark Wainwright, MD, and Michelle Elena Schober, MD, drove the identification and development of priorities for the pediatric neurocritical care community.

    View details for DOI 10.1007/s12028-023-01673-w

    View details for PubMedID 36759418

  • 23.4% SODIUM CHLORIDE ADMINISTRATION FOR NEUROLOGIC EMERGENCIES AT A CHILDREN'S HOSPITAL Vadasz, E., Moss, J., Rasmussen, L. LIPPINCOTT WILLIAMS & WILKINS. 2023: 405
  • Effect of clevidipine on intracranial pressure in pediatric neurosurgical patients: a single-center retrospective review. Journal of neurosurgery. Pediatrics Vadasz, E., Moss, J., Chang, N., Casazza, M., Rasmussen, L. 2022: 1-6

    Abstract

    OBJECTIVE: Hemodynamic management in pediatric neurosurgical patients is essential for maintaining cerebral perfusion pressure (CPP), avoiding hemorrhage, and preventing secondary neurological injury. Antihypertensive infusions approved for pediatrics are not widely studied in the pediatric neurosurgical population and may have adverse effects on intracranial pressure (ICP), contributing to reduced CPP. Clevidipine is an ultra-rapid-acting intravenous antihypertensive agent used for hemodynamic control in adult surgical patients. In pediatric patients, clevidipine is safe and effective in controlling blood pressure in the perioperative period, although studies evaluating its effect on ICP in neurosurgical patients are lacking. The objective of this research was to evaluate the effect of clevidipine on ICP in pediatric neurosurgical patients.METHODS: This single-center retrospective study involved patients admitted to the pediatric ICU between January 1, 2017, and December 31, 2020. Patients eligible for inclusion had ICP monitoring devices and received clevidipine infusion for a minimum of 6 hours postoperatively, with at least one ICP measurement pre- and postinfusion. Excluded patients had an elevated preinfusion ICP > 20 mm Hg. The primary outcome was the average change in ICP from preinfusion baseline to hours 6 to < 12, 12 to < 24, and 24 to < 48 of clevidipine infusion. Secondary outcomes included frequency of ICP measurements > 20 mm Hg, CPP measurements < 50 mm Hg, treatment failure defined by a need for concurrent antihypertensive infusion, and frequency of elevated serum triglycerides > 200 mg/dL. Descriptive data were expressed as frequency with percentage or median with interquartile range as appropriate. Analysis of continuous outcome variable data involved Mann-Whitney U-tests with an alpha significance of 0.05.RESULTS: Data from 47 patients were included in the analysis. The average change in ICP from preinfusion baseline to 48 hours was < 1 mm Hg. Of 3025 total postinfusion ICP measurements in 47 patients, 67 measurements (2.2%) in 13 patients (28%) were > 20 mm Hg. CPP measurements < 50 mm Hg occurred in 16 of 45 patients (36%). Three patients (6.4%) required use of a secondary antihypertensive medication infusion, and 5 of 14 patients (36%) had serum triglycerides > 200 mg/dL.CONCLUSIONS: Use of clevidipine had minimal effect on ICP. The results of this study suggest that clevidipine is effective at safely maintaining ICP and CPP measurements without detrimental adverse effects in pediatric neurosurgical patients.

    View details for DOI 10.3171/2022.11.PEDS22255

    View details for PubMedID 36681961

  • Exploring Trends in Neuromonitoring Use in a General Pediatric ICU: The Need for Standardized Guidance. Children (Basel, Switzerland) Chang, N., Rasmussen, L. 2022; 9 (7)

    Abstract

    Neuromonitoring has become more standardized in adult neurocritical care, but the utility of different neuromonitoring modalities in children remains debated. We aimed to describe the use of neuromonitoring in critically ill children with and without primary neurological diseases. We conducted a retrospective review of patients admitted to a 32-bed, non-cardiac PICU during a 12-month period. Neuro-imaging, electroencephalogram (EEG), cerebral oximetry (NIRS), automated pupillometry, transcranial doppler (TCD), intracranial pressure (ICP) monitoring, brain tissue oxygenation (PbtO2), primary diagnosis, and outcome were extracted. Neuromonitoring use by primary diagnosis and associations with outcome were observed. Of 1946 patients, 420 received neuro-imaging or neuromonitoring. Primary non-neurological diagnoses most frequently receiving neuromonitoring were respiratory, hematologic/oncologic, gastrointestinal/liver, and infectious/inflammatory. The most frequently used technologies among non-neurological diagnoses were neuro-imaging, EEG, pupillometry, and NIRS. In the multivariate analysis, pupillometry use was associated with mortality, and EEG, NIRS, and neuro-imaging use were associated with disability. Frequencies of TCD and PbtO2 use were too small for analysis. Neuromonitoring is prevalent among various diagnoses in the PICU, without clear benefit on outcomes when used in an ad hoc fashion. We need standard guidance around who, when, and how neuromonitoring should be applied to improve the care of critically ill children.

    View details for DOI 10.3390/children9070934

    View details for PubMedID 35883918

  • Major tumor regressions in H3K27M-mutated diffuse midline glioma (DMG) following sequential intravenous (IV) and intracerebroventricular (ICV) delivery of GD2-CAR T cells Majzner, R. G., Mahdi, J., Ramakrishna, S., Patel, S., Chinnasamy, H., Yeom, K., Schultz, L., Barsan, V., Richards, R., Campen, C., Reschke, A., Toland, A., Baggott, C., Mavroukakis, S., Egeler, E., Moon, J., Jacobs, A., Yamabe-Kwong, K., Rasmussen, L., Nie, E., Green, S., Kunicki, M., Fujimoto, M., Ehlinger, Z., Reynolds, W., Prabhu, S., Warren, K. E., Cornell, T., Partap, S., Fisher, P., Grant, G., Vogel, H., Sahaf, B., Davis, K., Feldman, S., Monje, M., Mackall, C. L. AMER ASSOC CANCER RESEARCH. 2022
  • MAJOR TUMOR REGRESSIONS IN H3K27M-MUTATED DIFFUSE MIDLINE GLIOMA (DMG) FOLLOWING SEQUENTIAL INTRAVENOUS (IV) AND INTRACEREBROVENTRICULAR (ICV) DELIVERY OF GD2-CAR T-CELLS Monje, M., Majzner, R., Mahdi, J., Ramakrishna, S., Patel, S., Chinnasamy, H., Yeom, K., Schultz, L., Barsan, V., Richards, R., Campen, C., Reschke, A., Toland, A., Baggott, C., Mavroukakis, S., Egeler, E., Moon, J., Jacobs, A., Yamabe-Kwong, K., Rasmussen, L., Nie, E., Green, S., Kunicki, M., Fujimoto, M., Ehlinger, Z., Reynolds, W., Prabhu, S., Warren, K. E., Cornell, T., Partap, S., Fisher, P., Grant, G., Vogel, H., Sahaf, B., Davis, K., Feldman, S., Mackall, C. OXFORD UNIV PRESS INC. 2022: 20-21
  • A PHASE I TRIAL OF PANOBINOSTAT FOLLOWING RADIATION THERAPY IN CHILDREN WITH DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) OR H3K27M-MUTATED THALAMIC DIFFUSE MIDLINE GLIOMA (DMG): REPORT FROM THE PEDIATRIC BRAIN TUMOR CONSORTIUM (PBTC-047) Monje, M., Cooney, T., Glod, J., Huang, J., Baxter, P., Vinitsky, A., Kilburn, L., Robison, N. J., Peer, C. J., Figg, W. D., Fouladi, M., Fangusaro, J., Onar-Thomas, A., Dunkel, I. J., Warren, K. E. OXFORD UNIV PRESS INC. 2022: 19
  • Continuing Care For Critically Ill Children Beyond Hospital Discharge: Current State of Follow-up. Hospital pediatrics Williams, C. N., Hall, T. A., Francoeur, C., Kurz, J., Rasmussen, L., Hartman, M. E., O'meara, A. I., Ferguson, N. M., Fink, E. L., Walker, T., Drury, K., Carpenter, J. L., Erklauer, J., Press, C., Wainwright, M. S., Lovett, M., Dapul, H., Murphy, S., Risen, S., Guerriero, R. M., Woodruff, A., Guilliams, K. P. 2022

    Abstract

    OBJECTIVES: Survivors of the PICU face long-term morbidities across health domains. In this study, we detail active PICU follow-up programs (PFUPs) and identify perceptions and barriers about development and maintenance of PFUPs.METHODS: A web link to an adaptive survey was distributed through organizational listservs. Descriptive statistics characterized the sample and details of existing PFUPs. Likert responses regarding benefits and barriers were summarized.RESULTS: One hundred eleven respondents represented 60 institutions located in the United States (n = 55), Canada (n = 3), Australia (n = 1), and the United Kingdom (n = 1). Details for 17 active programs were provided. Five programs included broad PICU populations, while the majority were neurocritical care (53%) focused. Despite strong agreement on the need to assess and treat morbidity across multiple health domains, 29% were physician only programs, and considerable variation existed in services provided by programs across settings. More than 80% of all respondents agreed PFUPs provide direct benefits and are essential to advancing knowledge on long-term PICU outcomes. Respondents identified "lack of support" as the most important barrier, particularly funding for providers and staff, and lack of clinical space, though successful programs overcome this challenge using a variety of funding resources.CONCLUSIONS: Few systematic multidisciplinary PFUPs exist despite strong agreement about importance of this care and direct benefit to patients and families. We recommend stakeholders use our description of successful programs as a framework to develop multidisciplinary models to elevate continuity across inpatient and outpatient settings, improve patient care, and foster collaboration to advance knowledge.

    View details for DOI 10.1542/hpeds.2021-006464

    View details for PubMedID 35314865

  • GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature Majzner, R. G., Ramakrishna, S., Yeom, K. W., Patel, S., Chinnasamy, H., Schultz, L. M., Richards, R. M., Jiang, L., Barsan, V., Mancusi, R., Geraghty, A. C., Good, Z., Mochizuki, A. Y., Gillespie, S. M., Toland, A. M., Mahdi, J., Reschke, A., Nie, E., Chau, I. J., Rotiroti, M. C., Mount, C. W., Baggott, C., Mavroukakis, S., Egeler, E., Moon, J., Erickson, C., Green, S., Kunicki, M., Fujimoto, M., Ehlinger, Z., Reynolds, W., Kurra, S., Warren, K. E., Prabhu, S., Vogel, H., Rasmussen, L., Cornell, T. T., Partap, S., Fisher, P. G., Campen, C. J., Filbin, M. G., Grant, G., Sahaf, B., Davis, K. L., Feldman, S. A., Mackall, C. L., Monje, M. 2022

    Abstract

    Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMG) are universally lethal paediatric central nervous system tumours1. We previously discovered that the disialoganglioside GD2 is highly expressed on H3K27M-mutant glioma cells and demonstrated promising preclinical efficacy of GD2-directed chimeric antigen receptor (CAR) T cells2, providing the rationale for a first-in-human Phase 1 clinical trial (NCT04196413). Because CAR T-cell-induced brainstem inflammation can result in obstructive hydrocephalus, increased intracranial pressure, and dangerous tissue shifts, neurocritical care precautions were incorporated. Here we present the clinical experience from the first four patients with H3K27M-mutant DIPG/DMG treated with GD2-CAR T cells (GD2-CART) at dose level 1 (1e6 GD2-CAR T cells/kg administered intravenously). Patients who exhibited clinical benefit were eligible for subsequent GD2-CAR T infusions administered intracerebroventricularly3. Toxicity was largely related to tumor location and reversible with intensive supportive care. On-target, off-tumor toxicity was not observed. Three of four patients exhibited clinical and radiographic improvement. Proinflammatory cytokines were increased in plasma and cerebrospinal fluid (CSF). Transcriptomic analyses of 65,598 single cells from CAR T cell products and CSF elucidate heterogeneity in response between subjects and administration routes. These early results underscore the promise of this approach for H3K27M+ DIPG/DMG therapy.

    View details for DOI 10.1038/s41586-022-04489-4

    View details for PubMedID 35130560

  • Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C. Pediatric neurology Fink, E. L., Robertson, C. L., Wainwright, M. S., Roa, J. D., Lovett, M. E., Stulce, C., Yacoub, M., Potera, R. M., Zivick, E., Holloway, A., Nagpal, A., Wellnitz, K., Czech, T., Even, K. M., Brunow de Carvalho, W., Rodriguez, I. S., Schwartz, S. P., Walker, T. C., Campos-Mino, S., Dervan, L. A., Geneslaw, A. S., Sewell, T. B., Pryce, P., Silver, W. G., Lin, J. E., Vargas, W. S., Topjian, A., Alcamo, A. M., McGuire, J. L., Dominguez Rojas, J. A., Munoz, J. T., Hong, S. J., Muller, W. J., Doerfler, M., Williams, C. N., Drury, K., Bhagat, D., Nelson, A., Price, D., Dapul, H., Santos, L., Kahoud, R., Francoeur, C., Appavu, B., Guilliams, K. P., Agner, S. C., Walson, K. H., Rasmussen, L., Janas, A., Ferrazzano, P., Farias-Moeller, R., Snooks, K. C., Chang, C. H., Yun, J., Schober, M. E., Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) Investigators 1800; 128: 33-44

    Abstract

    BACKGROUND: Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C).METHODS: Multicenter, cross-sectional study of neurological manifestations in children aged <18years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed.RESULTS: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P<0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P<0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P<0.05.CONCLUSIONS: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.

    View details for DOI 10.1016/j.pediatrneurol.2021.12.010

    View details for PubMedID 35066369

  • GD2 CAR T cells mediate clinical activity and manageable toxicity in children and young adults with DIPG and H3K27M-mutated diffuse midline gliomas. Majzner, R. G., Ramakrishna, S., Mochizuki, A., Patel, S., Chinnasamy, H., Yeom, K., Schultz, L., Richards, R., Campen, C., Reschke, A., Mahdi, J., Toland, A., Baggott, C., Mavroukakis, S., Egeler, E., Moon, J., Landrum, K., Erickson, C., Rasmussen, L., Barsan, V., Tamaresis, J. S., Marcy, A., Kunicki, M., Fujimoto, M., Ehlinger, Z., Kurra, S., Cornell, T., Partap, S., Fisher, P., Grant, G., Vogel, H., Sahaf, B., Davis, K., Feldman, S., Mackall, C. L., Monje, M. AMER ASSOC CANCER RESEARCH. 2021
  • SINGLE CELL RNA SEQUENCING FROM THE CSF OF SUBJECTS WITH H3K27M+DIPG/DMG TREATED WITH GD2 CAR T-CELLULAR THERAPY Mochizuki, A., Ramakrishna, S., Good, Z., Patel, S., Chinnasamy, H., Yeom, K., Schultz, L., Richards, R., Campen, C., Reschke, A., Mahdi, J., Toland, A., Baggot, C., Mavroukakis, S., Egeler, E., Moon, J., Landrum, K., Erickson, C., Rasmussen, L., Barsan, V., Tamaresis, J., Marcy, A., Kunicki, M., Celones, M., Ehlinger, Z., Kurra, S., Cornell, T., Partap, S., Fisher, P., Grant, G., Vogel, H., Davis, K., Feldman, S., Sahaf, B., Majzner, R., Mackall, C., Monje, M. OXFORD UNIV PRESS INC. 2021: 39
  • Characteristics of Pediatric Extracorporeal Membrane Oxygenation Programs in the United States and Canada. ASAIO journal (American Society for Artificial Internal Organs : 1992) Troy, L. n., Su, F. n., Kilbaugh, T. n., Rasmussen, L. n., Kuo, T. n., Jett, E. n., Cornell, T. n., Berg, M. n., Haileselassie, B. n. 2020

    Abstract

    The aim of this study was to evaluate the current infrastructure and practice characteristics of pediatric extracorporeal membrane oxygenation (ECMO) programs. A 40-question survey of center-specific demographics, practice structure, program experience, and support network utilized to cannulate and maintain a pediatric patient on ECMO was designed via a web-based survey tool. The survey was distributed to pediatric ECMO programs in the United States and Canada. Of the 101 centers that were identified to participate, 41 completed the survey. The majority of responding centers are university affiliated (73%) and have an intensive care unit (ICU) with 15-25 beds (58%). Extracorporeal membrane oxygenation has been offered for >10 years in 85% of the centers. The median number of total cannulations per center in 2017 was 15 (interquartile range [IQR] = 5-30), with the majority occurring in the cardiovascular intensive care unit (median = 13, IQR = 5-25). Fifty-seven percent of responding centers offer ECPR, with a median number of four cases per year (IQR = 2-7). Most centers cannulate in an operating room or ICU; 11 centers can cannulate in the pediatric ED. Sixty-three percent of centers have standardized protocols for postcannulation management. The majority of protocols guide anticoagulation, sedation, or ventilator management; left ventricle decompression and reperfusion catheter placement are the least standardized procedures. The majority of pediatric ECMO centers have adopted the infrastructure recommendations from the Extracorporeal Life Support Organization. However, there remains broad variability of practice characteristics and organizational infrastructure for pediatric ECMO centers across the United States and Canada.

    View details for DOI 10.1097/MAT.0000000000001311

    View details for PubMedID 33181543

  • NAUSEA AND VOMITING AFTER CRANIOTOMY IN THE PEDIATRIC ICU: INCIDENCE AND VARIATIONS IN PRACTICE Chang, N., Duethman, L., Young, N., Rasmussen, L. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • Sedation and Analgesia in Brain-Injured Children Sedation and Analgesia for the Pediatric Intensivist: A Clinical Guide Rasmussen, L. Springer. 2020; 1
  • INFRASTRUCTURE AND PRACTICE CHARACTERISTICS OF PEDIATRIC ECMO PROGRAMS ACROSS NORTH AMERICA Troy, L., Su, F., Berg, M., Rasmussen, L., Kuo, T., Jett, E., Jacobs, K., Haileselassie, B. LIPPINCOTT WILLIAMS & WILKINS. 2019
  • Trauma Bay Disposition of Infants and Young Children With Mild Traumatic Brain Injury and Positive Head Imaging Pediatric Critical Care Medicine Noje, C., Jackson, E., Nasr, I., Costabile, P., Cerullo, M., Hoops, K., Rasmussen, L., Henderson, E., Ziegfeld, S., Puett, L., Robertson , C. 2019
  • A Case Series of Parechovirus Encephalopathy: Apnea and Autonomic Dysregulation in Critically Ill Infants JOURNAL OF CHILD NEUROLOGY Ristagno, E. H., Bhalla, S. C., Rasmussen, L. K. 2018; 33 (12): 788–93

    Abstract

    This article aims to describe a rare cause of severe encephalitis in 2 cases of infants with signs of intracranial hypertension and severe autonomic dysregulation. The authors conclude that human parechoviruses are becoming a more recognized cause of encephalitis because of the increasing use of rapid detection methods. With early recognition of this clinical entity, improved care can be administered.

    View details for DOI 10.1177/0883073818789317

    View details for Web of Science ID 000444976000007

    View details for PubMedID 30105932

  • Traumatic Injury Leads to Inflammation and Altered Tryptophan Metabolism in the Juvenile Rabbit Brain JOURNAL OF NEUROTRAUMA Zhang, Z., Rasmussen, L., Saraswati, M., Koehler, R. C., Robertson, C., Kannan, S. 2019; 36 (1): 74–86
  • Neurocritical Care for Severe Pediatric Traumatic Brain Injury Rasmussen, L., Raghupathi, R., Lang Chen , S., Huh, J., Su, F. Medscap Drugs and Diseases. 2018
  • Albuterol Use in Children Hospitalized with Human Metapneumovirus Respiratory Infection INTERNATIONAL JOURNAL OF PEDIATRICS Rasmussen, L. K., Schuette, J., Spaeder, M. C. 2016: 7021943

    Abstract

    Introduction. Human metapneumovirus (HMPV) is a paramyxovirus from the same subfamily as respiratory syncytial virus (RSV) and causes similar acute lower respiratory tract infection. Albuterol in the setting of acute RSV infection is controversial and has not yet been studied in HMPV. We sought to determine the frequency of albuterol use in HMPV infection and the association between albuterol administration and patient outcomes. Methods. We conducted a retrospective cohort study identifying all patients hospitalized in a tertiary care children's hospital with laboratory-confirmed HMPV infection between January 2010 and December 2010. Results. There were 207 patients included in the study; 57% had a chronic medical condition. The median hospital length of stay was 3 days. Only 31% of patients in the study had a documented wheezing history, while 69% of patients received at least one albuterol treatment. There was no difference in length of stay between patients who received albuterol and those who did not. Conclusion. There is a high frequency of albuterol use in children hospitalized with HMPV infection. As with RSV, evidence may not support routine use of bronchodilators in patients with acute HMPV respiratory infection. Research involving additional patient outcomes and illness severity indicators would be useful in future studies.

    View details for PubMedID 26925109

    View details for PubMedCentralID PMC4748140

  • PERIPHERAL IMMUNE RESPONSE AFTER PEDIATRIC TRAUMATIC BRAIN INJURY IN RABBIT Rasmussen, L., Zhang, Z., Saraswati, M., Kannan, S., Robertson, C. MARY ANN LIEBERT, INC. 2015: A88
  • Infrastructure and Practice Characteristics of Pediatric ECMO Programs in the US and Canada Society of Critical Care Medicine Troy , L., Su, F., Berg, M., Rasmussen , L., Kuo, T., Jett, E., Jacobs, K., Haileselassie , B. 2019