P. Pearl O'Rourke

Delayed repair and preoperative ECMO does not improve survival in high-risk congenital diaphragmatic hernia

It has been suggested that delayed repair with preoperative stabilization might improve survival in high-risk (symptomatic within 6 hours of birth) congenital diaphragmatic hernia (CDH). This study compares the results of immediate operation versus delayed repair using extracorporeal membrane oxygenation (ECMO) when necessary. Since we first used ECMO in 1984, 101 high-risk CDH infants have been treated. Prior to 1987, we used immediate repair and postoperative ECMO if necessary. Between 1987 and 1990 we combined delayed operation (24 to 36 hours) with preoperative ECMO as necessary. No infant in this series was excluded from ECMO therapy unless absolute contraindications existed (prematurity, intracranial hemorrhage, or other major anomalies). Fifty-five patients received immediate operation and 46 had delayed repair. The two groups were comparable populations based on gestational age, birth weight, age at onset of symptoms, Apgar scores, best postductal PO2 (BPDPO2), and frequency of antenatal diagnosis. There was no statistically significant difference in overall survival between the two groups. Differences in survival among subpopulations (BPDPO2 greater than 100 or less than 100, antenatal diagnosis, inborn v outborn) also are not significant. The requirement for ECMO was similar in both groups. Survivors in the delayed repair group were ventilated longer and on ECMO longer, but had fewer late deaths (greater than 21 days) and fewer pulmonary sequelae (O2 dependency at discharge) than infants in the immediate repair group (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Global implementation of genomic medicine: We are not alone

Human-genomics programs work together worldwide to speed the translation of genomic medicine to the clinic. Around the world, innovative genomic-medicine programs capitalize on singular capabilities arising from local health care systems, cultural or political milieus, and unusual selected risk alleles or disease burdens. Such individual efforts might benefit from the sharing of approaches and lessons learned in other locales. The U.S. National Human Genome Research Institute and the National Academy of Medicine recently brought together 25 of these groups to compare projects, to examine the current state of implementation and desired near-term capabilities, and to identify opportunities for collaboration that promote the responsible practice of genomic medicine. Efforts to coalesce these groups around concrete but compelling signature projects should accelerate the responsible implementation of genomic medicine in efforts to improve clinical care worldwide.

Halothane in status asthmaticus.

The authors administered halothane anesthesia to treat a child with status asthmaticus that was refractory to conventional pharmacological therapy and mechanical ventilation. Halothane is an inhalation anesthetic with potent bronchodilator properties. Marked improvement in gas exchange occurred in this patient after 10 min of treatment with halothane. The pharmacology of halothane is reviewed and a possible role for its use in childhood asthma is proposed.

Neurological Complications of Hemolytic-Uremic Syndrome

Of 78 children identified with hemolytic-uremic syndrome at the Childrens Hospital, Boston, from 1976 to 1986, 16 patients (20.5%) had neurological manifestations during their hospitalization. The most common manifestations were significant alterations in consciousness (coma, stupor) in 12 patients, and either generalized or partial seizures in ten patients. Others included hemiplegia (4 patients), decerebrate posturing (3), cortical blindness (2), hallucinations (1), and dystonic posturing (1). Cranial computed tomographic scans were abnormal in eight of 11 patients scanned. The abnormalities included diffuse cerebral edema (4 patients), large vessel infarctions (3), diffuse multiple small infarcts (4), and multiple hemorrhages (1). Five patients died as a result of their central nervous system complications, and six had neurological sequelae at discharge. Five patients recovered and at discharge had no evidence of neurological dysfunction. (J Child Neurol 1989;4:108-113).

The effect of extracorporeal membrane oxygenation on the survival of neonates with high-risk congenital diaphragmatic hernia: 45 cases from a single institution.

At The Childrens Hospital, Boston (TCH), in the 3 years before extracorporeal membrane oxygenation (ECMO) was available, infants with high-risk congenital diaphragmatic hernia (CDH) had a 47% survival rate. In February 1984, ECMO was introduced and offered to all high-risk CDH infants with a 100% predicted mortality. Since February 1984, 45 infants with high-risk CDH presented to TCH. Twenty-six (58%) were supported with ECMO; 19 (42%) never met the criteria for 100% predicted mortality and were supported with conventional mechanical ventilation (CMV). Overall survival was 49%. Nine (35%) of the 26 ECMO patients survived. Thirteen (68%) of the 19 CMV patients survived. Although there was no change in survival, there was a change in the cause of death. Deaths in the ECMO group were either early (n = 8, secondary to a complication of ECMO or lack of pulmonary improvement) or late (n = 9). The late deaths were infants who were successfully weaned from ECMO, never weaned from CMV, and who died secondary to complications of chronic lung disease.

The OHRP and SUPPORT

A group of medical ethicists and pediatricians asks for reconsideration of the recent Office for Human Research Protections decision about informed consent in SUPPORT.

Return of research results from genomic biobanks: cost matters.

Return of individual research results (IRRs) to study participants has been, and continues to be, hotly debated. The role of biobanks in the return of research results had received little attention until the recent publication from Susan Wolf et al.,1 which presents a detailed discussion and 10 recommendations regarding the return of results from biobanks. The authors propose that if reidentification of an individual participant (whom they also call a “contributor”) is possible, the biobank, as the central hub in a biobank research system, should enable the system to (i) clarify the criteria for evaluating findings and develop a list of returnable findings; (ii) analyze a particular finding in relation to the aforementioned list/criteria; (iii) reidentify the individual participant/contributor; and (iv) recontact them to offer the finding. Wolf et al.1 propose that the biobank would bear the long-term responsibility for the return of incidental findings (IFs) and IRRs rather than the investigators themselves. These recommendations neither sufficiently reflect the wide variability in both the purpose and nature of biobanks nor do they take into account the associated costs to biobanks and the research system. Biobanks encompass disease-specific and healthy cohorts and range from small collections in individual laboratories to international collections involving many thousands of people.2

Centralized Banks for Human Embryonic Stem Cells: A Worthwhile Challenge

Centralized banking of human embryonic stem (hES) cells is an endeavor that can benefit individual research efforts and enhance international collaboration but is complicated by the fact that the science is rapidly evolving in an environment of heterogeneous laws, guidelines, and ethical standards. Written from the vantage point of regulatory professionals, this article provides an overview of the benefits of and challenges facing hESC banking enterprises in general with a focus on a global centralized banking effort.

Extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation is still a relatively new technology that has recently achieved recognition after initial clinical disappointment in the late 1970s. At present, it is considered standard therapy for the full-term infant with PPHN who fails CMV and extraordinary, heroic therapy for older children and adults with ARF or cardiac failure, or both. Currently, the emphasis is on developing new technologies for increasing safety and effectiveness. Areas of interest include heparinless circuits, carotid artery reconstruction, improved monitoring, and expanding applications of VV ECMO. As ECMO becomes safer and more effective, it is believed that new and expanding patient populations will emerge to include premature infants, earlier intervention in term infants, and more liberal application to pediatric and adult populations.

Effect of isoproterenol on measured theophylline levels.

Aggressive pharmacotherapy for the treatment of patients with severe status asthmaticus includes theophylline and beta-adrenergic agonists such as isoproterenol. We found that the measured theophylline level decreased when an isoproterenol infusion was started, and this decrease persisted throughout the entire exposure to isoproterenol. When the isoproterenol infusion was discontinued, the theophylline level increased. The etiology of this observed effect is unknown.