Outcome of extracorporeal membrane oxygenation support among children with methicillin-resistant Staphylococcus aureus infection: A single-center experience.

Introduction: The use of extracorporeal membrane oxygenation (ECMO) in children continues to increase nationally, including patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. Survival of pediatric patients with MRSA sepsis has not improved over the last 20 years. We sought to review our institutional experience and outcomes of ECMO support among children with MRSA infection.Methods: Children aged 0-19 years who received ECMO support from October 2014 to June 2021 were reviewed retrospectively. Patients with laboratory confirmed MRSA infections were identified.Results: Out of 88 unique pediatric patients requiring ECMO support, eight patients had documented MRSA infections. The duration of mechanical ventilation prior to ECMO initiation was an average of seven days (range 0.7 to 21.8 days). The median ECMO duration was 648.1 h (range 15.5 to 1580.5 h). Five patients were successfully decannulated; however, only two patients survived to discharge. The two surviving patients were both cannulated via VV-ECMO. Mechanical ventilation prior to ECMO was 4.5 and 21.8 days in these cases with run durations of 18.9 and 29.9 days, respectively.Conclusions: Our institutional survival of patients with MRSA on ECMO is lower than what has been reported in recent database studies, but notably, 62.5% were successfully decannulated. While both surviving patients were supported with VV-ECMO, there was no other clear trend in factors that contributed to survival. MRSA continues to be a source of significant morbidity and mortality among pediatric patients. On-going investigation of outcomes and factors contributing to survival in patients with MRSA infection on ECMO is warranted.

Development and Evaluation of I-PASS-to-PICU: A Standard Electronic Template to Improve Referral Communication for Interfacility Transfers to the Pediatric ICU.

BACKGROUND: Miscommunication during interfacility handoffs to a higher level of care can harm critically ill children. Adapting evidence-based handoff interventions to interfacility referral communication may prevent adverse events. The objective of this project was to develop and evaluate a standard electronic referral template (I-PASS-to-PICU) to improve communication for interfacility pediatric ICU (PICU) transfers. METHODS: I-PASS-to-PICU was iteratively developed in a single PICU. A core PICU stakeholder group collaboratively designed an electronic health record (EHR)-supported clinical note template by adapting elements from I-PASS, an evidence-based handoff program, to support information exchange between referring clinicians and receiving PICU physicians. I-PASS-to-PICU is a receiver-driven tool used by PICU physicians to guide verbal communication and electronic documentation during PICU transfer calls. The template underwent three cycles of iterative evaluation and redesign informed by individual and group interviews of multidisciplinary PICU staff, usability testing using simulated and actual referral calls, and debriefing with PICU physicians. RESULTS: Individual and group interviews with 21 PICU staff members revealed that relevant, accurate, and concise information was needed for adequate admission preparedness. Time constraints and secondhand information transmission were identified as barriers. Usability testing with six receiving PICU physicians using simulated and actual calls revealed good usability on the validated System Usability Scale (SUS), with a mean score of 77.5 (standard deviation 10.9). Fellows indicated that most fields were relevant and that the template was feasible to use. CONCLUSION: I-PASS-to-PICU was technically feasible, usable, and relevant. The authors plan to further evaluate its effectiveness in improving information exchange during real-time PICU practice.

Enhancement of the anti-melanoma response of Hu14.18K322A by αCD40 + CpG.

Targeted monoclonal antibodies (mAb) can be used therapeutically for tumors with identifiable antigens such as disialoganglioside GD2, expressed on neuroblastoma and melanoma tumors. Anti-GD2 mAbs (αGD2) can provide clinical benefit in patients with neuroblastoma. An important mechanism of mAb therapy is antibody-dependent cellular cytotoxicity (ADCC). Combinatorial therapeutic strategies can dramatically increase the anti-tumor response elicited by mAbs. We combined a novel αGD2 mAb, hu14.18K322A, with an immunostimulatory regimen of agonist CD40 mAb and class B CpG-ODN 1826 (CpG). Combination immunotherapy was more effective than the single therapeutic components in a syngeneic model of GD2-expressing B16 melanoma with minimal tumor burden. NK cell depletion in B6 mice showed that NK cells were required for the anti-tumor effect; however, anti-tumor responses were also observed in tumor-bearing SCID/beige mice. Thus, NK cell cytotoxicity did not appear to be essential. Peritoneal macrophages from anti-CD40 + CpG-treated mice inhibited tumor cells in vitro in an hu14.18K322A antibody-dependent manner. These data highlight the importance of myeloid cells as potential effectors in immunotherapy regimens utilizing tumor-specific mAb and suggest that further studies are needed to investigate the therapeutic potential of activated myeloid cells and their interaction with NK cells.

Hypercarbia in a Pediatric Patient With Relapsed Medulloblastoma.

Pediatric medulloblastoma is a common form of pediatric brain tumor and typically presents with progressive signs of increased intracranial pressure and ataxia. Relapse of the disease is most often diagnosed on surveillance imaging. We present the case of a 13-year-old boy with a previous history of medulloblastoma who presented with chronic hypercarbic respiratory failure as a symptom of a recurrent tumor. Imaging demonstrated a left cerebellar enhancing mass with leptomeningeal thickness and extension to the posterior medulla oblongata, which is the center for respiratory control. His hypercarbic respiratory failure represents a unique presentation of a central nervous system (CNS) tumor. Thus, this case illustrates the importance of thorough evaluation for CNS tumors involving the brainstem in patients with respiratory acidosis and no clear pulmonary etiology.

Tissue-Resident Memory T Cells in the Lungs Protect against Acute Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in young children. The T cell response plays a critical role in facilitating clearance of an acute RSV infection, and memory T cell responses are vital for protection against secondary RSV exposures. Tissue-resident memory (TRM) T cells have been identified as a subset of memory T cells that reside in nonlymphoid tissues and are critical for providing long-term immunity. There is currently limited information regarding the establishment and longevity of TRM T cell responses elicited following an acute RSV infection as well as their role in protection against repeated RSV infections. In this study, we examined the magnitude, phenotype, and protective capacity of TRM CD4 and CD8 T cells in the lungs of BALB/c mice following an acute RSV infection. TRM CD4 and CD8 T cells were established within the lungs and waned by 149 d following RSV infection. To determine the protective capacity of TRMs, FTY720 administration was used to prevent trafficking of peripheral memory T cells into the lungs prior to challenge of RSV-immune mice, with a recombinant influenza virus expressing either an RSV-derived CD4 or CD8 T cell epitope. We observed enhanced viral clearance in RSV-immune mice, suggesting that TRM CD8 T cells can contribute to protection against a secondary RSV infection. Given the protective capacity of TRMs, future RSV vaccine candidates should focus on the generation of these cell populations within the lung to induce effective immunity against RSV infection.