Embracing bioethics in neonatal intensive care, part II: case histories in neonatal ethics

Ethical treatment dilemmas are not new to the NICU. With technologic advances over the past 20 years, NICU care has developed rapidly, and survival rates have improved for some of the tiniest and most critically ill infants. In guiding clinical practice, however, standards in evidenced- based medicine have often superseded standards in evidence-based ethics. Neonatal nurses attain a more in-depth understanding of the clinical significance of the four principles of bioethics: autonomy, nonmaleficence, beneficence, and justice. Case studies illustrate the principles discussed.     

Stability of the high on-treatment platelet reactivity phenotype over time in clopidogrel-treated patients

Interindividual response variability to clopidogrel treatment is a well established phenomenon. In recent studies and ongoing large-scale trials where patients with high on-treatment platelet reactivity (HPR) to clopidogrel are being randomised to an intensified antiplatelet treatment, confirmation of the HPR phenotype is based on one single platelet function assessment. The stability of the HPR phenotype over time has never been investigated but should be considered crucial for justification of intensified antiplatelet treatment regimens beyond clinical trials. The goal of this study was to test for the stability of the HPR phenotype over time in clopidogrel-treated patients. Patients (n=31) under chronic clopidogrel treatment (75 mg/day) were investigated by serial adenosine diphosphate (ADP)-induced platelet aggregation assessment with multiple electrode aggregometry (MEA) on a Multiplate analyser and light transmission aggregometry (LTA) at three different time points (once per week) during monitored antiplatelet treatment. On the basis of a cut-off level approach (468 AU*min for MEA, 53% for LTA) patients were classified into patients with (n=27) or without (n=4) HPR. For MEA, the phenotype was stable in 93.5% (n=29) of patients whereas 6.5% (n=2) crossed the cut-off level. For LTA, the phenotype was stable in 68% (n=21) of patients whereas 32% (n=10) patients crossed the cut-off level (chi-square P=0.01 for comparison of phenotype stability between both assays). In conclusion, the HPR phenotype is stable over time in the majority of clopidogrel-treated patients. Comparative assessment of phenotype stability across available platelet function assays warrants further investigation.     

Cumulative perinatal steroids: child development of preterm infants

Within a small cohort study, it is unwise to make broad conclusions based upon preliminary findings. Future research should consider the fetus/infant in a state of evolution that is on a continuum from uterine life throughout the NICU stay. By conceptualizing cumulative PNS exposures and examining relationships with severity of illness and latent development of preterm infants, this study sought to add to the body of scientific knowledge in this area and challenge conventional wisdom. Concern should continue to exist for those children previously exposed to higher steroid treatment. To accurately evaluate steroid exposure, clinical researchers need to look back and quantify doses offered to patients to identify childhood outcomes that reflect potentially mixed blessings. The moratorium on PNS may have already altered clinical practice and limited usage of dexamethasone or led to substituting another steroid, hydrocortisone, about which even less is known. Thus, it seems that the search should continue for safer minimal dose steroid guidelines with a focus on cumulative exposure and close assessment of infant development throughout childhood.     

Therapeutic targeting of chemokine signaling in Multiple Sclerosis

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that is initiated and maintained by continuous migration of inflammatory immune cells from the periphery into the target organ. However, in autoimmunity, migration of immune cells is not only involved in the pathogenesis but also in the down-modulation of the autoimmune attack, which is probably mediated by the infiltration of certain regulatory immune cell populations inside the affected organs. The migratory activity of both proinflammatory and regulatory leucocytes is controlled by chemokines and their receptors. Thus, targeting the directed migration of immune cells and regulating leukocyte trafficking across the blood-brain barrier (BBB) by means of modulation of chemokine signaling receptors might open up new therapeutic avenues not only for MS but also for other autoimmune diseases. In this review we summarize the chemotactic signaling pathways known to be involved in neuroinflammation to date and the viability of these pathways as targets for therapeutic strategies.