Incidence of Acute Neurological Events in Neonates and Infants Undergoing Cardiac Surgery Using a High-Hematocrit/ High-Flow Bypass Strategy.

Background: The incidence of new acute neurological injury occurring in neonates and infants during cardiac surgery utilizing cardiopulmonary bypass is reportedly 3% to 5%. In 2013, we adopted a high flow rate, and high hematocrit bypass strategy, and sought to assess the incidence of early neurological injuries associated with this strategy. Methods: Neonates and infants undergoing cardiopulmonary bypass between January 2013 and December 2019 (n = 714) comprise the study. Adverse neurological events (ANEs) were defined as any abnormality of pupils, delayed awakening, seizures, focal neurological deficits, concerns prompting neurological consultation, or any abnormality on neurological imaging in the postoperative period. Our bypass strategy included a high flow rate (150-200 mL/kg/min), without reduction of flow rates during cooling and maintaining a target hematocrit on bypass > 32% with a terminal hematocrit of > 42%. Results: Median weight at the time of the procedure was 4.6 kg (IQR 3.6-6.1 kg) with the smallest patient weighing 1.36 kg. There were 46 premature patients (6.4%). There were 149 patients (20.9%) patients who underwent deep hypothermic circulatory arrest with a median time of 26 min (IQR 21-41 min). Hospital mortality was 3.5% (24/714, 95% CI: 2.28-5.13). The incidence of neurological events as defined above was 0.84% (6/714, 95% CI: 0.31-1.82). Neurological imaging identified ischemic injury in 4 patients and intraventricular hemorrhage in 2. Conclusions: High flow/high hematocrit bypass strategy was associated with a low incidence of ANE in this vulnerable population.

Strategies and techniques for percutaneous Veno-Arterial ECMO cannulation and decannulation in children.

OBJECTIVES: To describe the techniques used for percutaneous veno-arterial extracorporeal membrane oxygenation (VA-ECMO) cannulation and decannulation in children with the pediatric interventional cardiologist (PIC) as the primary operator, and present outcomes of this initial clinical experience. BACKGROUND: Percutaneous VA-ECMO during cardiopulmonary resuscitation (CPR) has been successfully performed in adults, but currently, not much data exists on children. METHODS: This is a single-center study including VA-ECMO cannulations performed by the PIC between 2019 and 2021. Efficacy was defined as the successful initiation of VA-ECMO without surgical cutdown. Safety was defined as the absence of additional procedures related to cannulation. RESULTS: Twenty-three percutaneous VA-ECMO cannulations were performed by PIC on 20 children with 100% success. Fourteen (61%) were performed during ongoing CPR, and nine for cardiogenic shock. The Median age was 15 (0.15-18) years, and the median weight was 65 (3.3-180) kg. All arterial cannulations were via the femoral artery except in one, 8-week-old infant who was cannulated in the carotid artery. A distal perfusion cannula was placed in the ipsilateral limb in 17 (78%). The median time from initiating cannulation to ECMO flow was 35 (13-112) minutes. Two patients required arterial graft placement at the time of decannulation and one needed below-knee amputation. ECMO support was maintained for a median of 4 (0.3-38) days. Thirty-day survival was 74%. CONCLUSION: Percutaneous VA-ECMO cannulations can be effectively performed, even during CPR with the Pediatric Interventional Cardiologist being the primary operator. This is an initial clinical experience. Future outcome studies compared with standard surgical cannulations are necessary to advocate routine percutaneous VA-ECMO in children.

Treatment of comatose patient from cyclobenzaprine overdose with therapeutic plasma exchange.

We present a case of a 15-year-old female who was admitted in a comatose state with no spontaneous respiratory effort and absence of brainstem reflexes after cyclobenzaprine ingestion. Due to severe presentation and recent ingestion of high plasma protein binding medication with long half-life, therapeutic plasma exchange (TPE) was performed and resulted in full neurological recovery. This case explores the role of TPE as an effective treatment option for life-threatening cyclobenzaprine overdose. TPE is generally beneficial for drugs that have a low volume of distribution and high plasma protein binding. Cyclobenzaprine is known to have a relatively high volume of distribution. However, in the case of drug intoxication with relatively high-volume distribution, high protein binding, and long half-life, TPE could be effective if it is conducted promptly.

Acute upper extremity flaccid paralysis in a 5year old child secondary to enterovirus infection.

The incidence of acute flaccid paralysis has been on a declining trend with the global efforts on eradication of polio virus. A few scattered clusters of acute flaccid paralysis associated with pathogens like enterovirus other than polio virus and flaviviruses have recently come to limelight. This is a case of acute onset flaccid paralysis of left upper extremity in a fully immunized 5 year old child in New York.

New interleukin-15 superagonist (IL-15SA) significantly enhances graft-versus-tumor activity.

Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors. Herein, we evaluated the effects of IL-15SA in recipients of allogeneic hematopoietic stem cell transplantation. Weekly administration of IL-15SA to transplant recipients significantly increased the number of CD8+ T cells (specifically CD44+ memory/activated phenotype) and NK cells. Intracellular IFN-γ and TNF-α secretion by CD8+ T cells increased in the IL-15SA-treated group. IL-15SA also upregulated NKG2D expression on CD8+ T cells. Moreover, IL-15SA enhanced proliferation and cytokine secretion of adoptively transferred CFSE-labeled T cells in syngeneic and allogeneic models by specifically stimulating the slowly proliferative and nonproliferative cells into actively proliferating cells.We then evaluated IL-15SA's effects on anti-tumor activity against murine mastocytoma (P815) and murine B cell lymphoma (A20). IL-15SA enhanced graft-versus-tumor (GVT) activity in these tumors following T cell infusion. Interestingly, IL-15 SA administration provided GVT activity against A20 lymphoma cells in the murine donor leukocyte infusion (DLI) model without increasing graft versus host disease. In conclusion, IL-15SA could be a highly potent T- cell lymphoid growth factor and novel immunotherapeutic agent to complement stem cell transplantation and adoptive immunotherapy.