Importance of anti-siphon devices in the treatment of pediatric hydrocephalus

The effects of an antisiphon device (ASD) on shunt flow and intracranial pressure (ICP) in 16 children with hypertensive hydrocephalus were examined using quantitative radionuclide shuntography (^99mTc) with the children in supine and sitting positions. The average age of these patients was 9.5 years. Results were compared with those recorded in 36 patients with adult normal-pressure hydrocephalus (NPH). The closing pressure levels of shunt valve used were low in 8 cases, medium in 7 and high in 1. Half the children (8) had shunt systems with, and the other 8 without, ASD. In the children who had the shunt system without ASD, sitting shunt flow was significantly greater than supine shunt flow, which indicated overdrainage. Conversely, in children who had the shunt system with ASD, supine shunt flow was greater than sitting shunt flow. Because ASD prevented overdrainage, ICP was higher with the shunt system with ASD than with the shunt system without ASD. Without ASD, sitting shunt flow of children was lower than that of adult patients with NPH because of the lower hydrostatic pressure, which correlated with their height. Conversely, in the presence of a shunt system with ASD, sitting shunt flow of children was greater than that of adults, because of the higher ICP and lower hydrostatic pressure. The effect of ASD was smaller in children than in adults, because positive pressure over the ASD was greater (hypertension vs normal pressure) and negative pressure under the ASD was less (short vs tall) in children than in adults. Thus, in children the ASD was effective in preventing overdrainage. An overfunction of the ASD, which has sometimes been observed in adult patients with NPH, was not encountered. The relationships among the function of the ASD and ICP, height and position of the ASD are discussed.Presented at the Consensus Conference: Hydrocephalus '92, Assisi, Italy, 26–30 April 1992     

Clinical Real‐Time Monitoring of Gaseous Microemboli in Pediatric Cardiopulmonary Bypass

We describe the occurrence and distribution of gaseous microemboli with real‐time monitoring in a pediatric cardiopulmonary bypass (CPB) circuit and in the cerebral circulation of patients using the Emboli Detection and Classification (EDAC) system and transcranial Doppler (TCD). Four patients (weights 3.2–13.8 kg) were studied. EDAC monitors were located on the venous line and on the postfilter arterial line to measure gaseous microemboli in the CPB circuit. TCD was used to measure high‐intensity transient signals (HITS) in the middle cerebral artery. Before the initiation of CPB, EDAC detected gaseous microemboli in two cases when giving volume through the arterial line. At the initiation of CPB, gross air appeared in the venous line and gaseous microemboli were detected in the arterial line in all patients. EDAC detected a total of 3192–14 699 gaseous microemboli in the arterial line during the whole CPB period, more than 99% of which were smaller than 40 microns. After cessation of CPB, EDAC detected gaseous microemboli in the arterial line in all cases. The TCD detected HITS in two cases (25 and 315), and detected no HITS in two cases. We observed that the venous line acted as a principal source of gaseous microemboli, particularly when using vacuum‐assisted venous drainage, and that a significant number of these gaseous microemboli smaller than 40 microns were subsequently transferred to the patient. Using EDAC and TCD together could strengthen the monitoring of gaseous microemboli in the extracorporeal circuit and cerebral circulation.     

Primary malignant vascular tumors of the liver in children: Angiosarcoma and epithelioid hemangioendothelioma

Primary malignant vascular neoplasms of the liver, angiosarcoma and epithelioid hemangioendothelioma, are extremely rare entities in the pediatric population. International Society for the Study of Vascular Anomalies classification system is recommended for the pathologic diagnosis of hepatic vascular lesions in this age group. In this article, we highlight the clinicopathologic characteristics of hepatic angiosarcoma and epithelioid hemangioendothelioma in the pediatric population. Hepatic angiosarcoma in children shows a slight female predominance with an average age of 40 mo at diagnosis. The distinct histologic features include whorls of atypical spindled cells and eosinophilic globules, in addition to the general findings of angiosarcoma. Histologic diagnosis of pediatric hepatic angiosarcoma is not always straightforward, and the diagnostic challenges are discussed in the article. Hepatic epithelioid hemangioendothelioma also demonstrates a female predominance, but is more commonly identified in adolescents (median age at diagnosis: 12 years). Histologically, the lesion is characterized by epithelioid cells and occasional intracytoplasmic lumina with a background of fibromyxoid stroma. While WWTR1-CAMTA1 and YAP1-TFE3 fusions have been associated with epithelioid hemangioendothelioma, there are currently no known signature genetic alterations seen in pediatric hepatic angiosarcoma. Advancement in molecular pathology, particularly for pediatric hepatic angiosarcoma, is necessary for a better understanding of the disease biology, diagnosis, and development of targeted therapies.     

Safety and Efficacy of Chimeric Antigen Receptor T-Cell Therapy in Children With Central Nervous System Leukemia

Backgroundchimeric antigen receptor–modified T cell (CAR-T) therapy is an effective and promising treatment for refractory and multiply relapsed B-cell acute lymphoblastic leukemia (B-ALL). Because of its side effects and poor responses such as neurotoxicity and cytokine release syndrome, patients with central nervous system leukemia were excluded in most previous clinical trials of CAR-T treatment.Patients and MethodsWe enrolled 3 B-ALL patients with central nervous system leukemia relapse. They were infused with CD19-specific CAR-Ts, and their clinical responses were evaluated by bone marrow smear, flow cytometry, and cytogenetic alterations detected by quantitative PCR, interleukin-6, and the expansion and persistence of circulating CAR-Ts in peripheral blood and cerebrospinal fluid.ResultsAfter CAR-T infusion, 2 of the 3 patients experienced bone marrow minimal residual disease–negative complete remission, and all patients tested negative for residual leukemia cells in cerebrospinal fluid tested by flow cytometry. These 3 patients experienced grade 2 or 3 cytokine release syndrome, which resolved completely after symptomatic treatment. None experienced neurotoxicity or needed further intensive care.ConclusionCAR-T infusion is a potentially effective treatment for relapsed/refractory B-ALL patients with central nervous system involvement.     

Phase 2 Clinical Trial of Infusing Haploidentical K562-mb15-41BBL–Activated and Expanded Natural Killer Cells as Consolidation Therapy for Pediatric Acute Myeloblastic Leukemia

BackgroundAcute myeloid leukemia (AML) accounts for approximately 20% of pediatric leukemia cases; 30% of these patients experience relapse. The antileukemia properties of natural killer (NK) cells and their safety profile have been reported in AML therapy. We proposed a phase 2, open, prospective, multicenter, nonrandomized clinical trial for the adoptive infusion of haploidentical K562-mb15-41BBL–activated and expanded NK (NKAE) cells as a consolidation strategy for children with favorable and intermediate risk AML in first complete remission after chemotherapy (NCT02763475).Patients and MethodsBefore the NKAE cell infusion, patients underwent a lymphodepleting regimen. After the NKAE cell infusion, patients were administered low doses (1 × 10⁶/IU/m²) of subcutaneous interleukin-2. The primary study endpoint was AML relapse-free survival. We needed to include 35 patients to demonstrate a 50% reduction in relapses.ResultsSeven patients (median age, 7.4 years; range, 0.78-15.98 years) were administered 13 infusions of NKAE cells, with a median of 36.44 × 10⁶ cells/kg (range, 6.92 × 10⁶ to 193.2 × 10⁶ cells/kg). We observed chimerism in 4 patients (median chimerism, 0.065%; range, 0.05-0.27%). After a median follow-up of 33 months, the disease of 6 patients (85.7%) remained in complete remission. The 3-year overall survival was 83.3% (95% confidence interval, 68.1-98.5), and the cumulative 3-year relapse rate was 28.6% (95% confidence interval, 11.5-45.7). The study was terminated early because of low patient recruitment.ConclusionThis study emphasizes the difficulties in recruiting patients for cell therapy trials, though NKAE cell infusion is safe and feasible. However, we cannot draw any conclusions regarding efficacy because of the small number of included patients and insufficient biological markers.     

Associations of Participation-Focused Strategies and Rehabilitation Service Use With Caregiver Stress After Pediatric Critical Illness

Objective(s)

Determine the associations between having participation-focused strategies and receiving rehabilitation services in the pediatric intensive care unit (PICU) with caregiver stress over 6 months post-PICU discharge.