We sought to determine the current practices of neonatologists in their management of extremely low-birth-weight (< 1000 g) infants. We directly mailed an anonymous survey to the medical directors of ...809 neonatal intensive care units in the United States. More than one-third of those surveyed responded, with a substantial majority from intensive care (level III) nurseries or extracorporeal membrane oxygenation centers. Academic centers and private practice environments were both well represented. Some traditional practices have changed, such as beginning resuscitation with 40% rather than 100% oxygen. Many practices vary based on whether neonates are cared for in private versus academic centers, including initial resuscitation method, type of ventilation used, use of intraventricular hemorrhage prophylaxis, and routine antibiotic therapy. Parenteral nutrition composition and the use of inhaled nitric oxide differ based on the responding center's participation in clinical trials. The number of years in practice as a neonatologist does not affect practice decisions. Among all our findings, the prevalence of one potentially harmful practice, the continued use of dexamethasone for corticosteroid therapy, was particularly noteworthy. In conclusion, the strength of evidence does not always predict whether practices are adopted or abandoned. Further research is necessary to clarify the optimal management for this high-risk patient population.
The PDA: TO LEave it alone or Respond And Treat Early trial compared the effects of 2 strategies for treatment of patent ductus arteriosus (PDA) in infants <280/7 weeks of gestation; however 137 ...potentially eligible infants were not recruited and received treatment of their PDA outside the PDA-TOLERATE trial due to “lack-of-physician-equipoise” (LPE). Despite being less mature and needing more respiratory support, infants with LPE had lower rates of mortality than enrolled infants. Infants with LPE treated before day 6 had lower rates of late respiratory morbidity than infants with LPE treated ≥day 6.
ClinicalTrials.gov: NCT01958320.
In the PDA-TOLERATE trial, persistent (even for several weeks) moderate to large patent ductus arteriosus (PDA) was not associated with an increased risk of BPD when the infant required <10 days of ...intubation. However, in infants requiring intubation for ≥10 days, prolonged PDA exposure (≥11 days) was associated with an increased risk of moderate/severe BPD.
We performed a multicenter study of preterm infants, who were about to undergo patent ductus arteriosus ligation, to determine whether echocardiographic indices of impaired myocardial performance ...were associated with subsequent development of catecholamine-resistant hypotension following ligation.
A standardized treatment approach for hypotension was followed at each center. Infants were considered to have catecholamine-resistant hypotension if their dopamine infusion was > 15 μg kg(-1)min(-1). Echocardiograms and cortisol measurements were obtained between 6 and 14 h after the ligation (prior to the presence of catecholamine-resistant hypotension).
Forty-five infants were enrolled, 10 received catecholamines (6 were catecholamine-responsive and 4 developed catecholamine-resistant hypotension). Catecholamine-resistant hypotension was not associated with decreased preload, shortening fraction or ventricular output. Infants with catecholamine-resistant hypotension had significantly lower levels of systemic vascular resistance and postoperative cortisol concentration.
We speculate that low cortisol levels and impaired vascular tone may have a more important role than impaired cardiac performance in post-ligation catecholamine-resistant hypotension.
Abstract Prematurity is associated with poor neurodevelopmental outcomes, and laws mandate the provision of early intervention services to those infants with disability. However, it is often ...difficult to identify early which infants would benefit most from these services. The Neurobiologic Risk Score (NBRS) and the Neurodevelopmental Risk Exam (NRE) are instruments used to assess infants at near-term corrected age. These instruments have been shown to correlate with later developmental outcomes. However, the environment of the neonatal intensive care unit (NICU) has changed since the NBRS and NRE were first validated, and it is not known whether they are still able to accurately predict future developmental outcomes. The objective of this study was therefore to examine the ability of the NBRS and NRE, both alone and in combination with socio-economic variables, to predict future developmental outcomes in the contemporary NICU. The subjects were 219 neonates of less than 32 weeks' gestational age discharged from the NICU between November 2001 and December 2006 who had undergone both the NBRS and NRE. Infants were assessed at chronological age 6, 12 and 24 months, with developmental quotients being assigned at these ages. Parental socio-economic data were also collected and analysed. The hypothesis was that the NBRS and NRE would be less effective at predicting neurodevelopmental outcomes in the contemporary NICU. The best measure of future developmental outcome is likely to need to include both neurobiological and socio-economic risk factors.
Pheochromocytomas are chromaffin cell-derived neuroendocrine tumors. There is presently no cure for metastatic pheochromocytoma and no reliable way to distinguish malignant from benign tumors before ...the development of metastases. In order to successfully manage pheochromocytoma, it is necessary to better understand the biological determinants of tumor behavior. For this purpose, we have recently established a mouse model of metastatic pheochromocytoma using tail vein injection of mouse pheochromocytoma (MPC) cells. We optimized this model modifying the number of cells injected, length of trypsin pre-treatment, and incubation temperature and duration for the MPC cells before injection, and by serial passage and re-selection of tumors exhibiting the metastatic phenotype. We evaluated the effect of these modifications on tumor growth using serial in vivo Magnetic Resonance Imaging studies. These results show that number of cells injected, the pre-injection incubation temperature, and duration of trypsin treatment are important factors to produce faster growing, more aggressive tumors that yielded secondary metastatic lesions. Serial harvest, culture and re-selection of metastatic liver lesions produced even more aggressive pheochromocytoma cells that retained their biochemical phenotype. Microarray gene expression comparison and quantitative real-time PCR of these more aggressive cells to the MPC-parental cell line identified genes that may be important for the metastatic process.
Prematurity is associated with poor neurodevelopmental outcomes, and laws mandate the provision of early intervention services to those infants with disability. However, it is often difficult to ...identify early which infants would benefit most from these services. The Neurobiologic Risk Score (NBRS) and the Neurodevelopmental Risk Exam (NRE) are instruments used to assess infants at near-term corrected age. These instruments have been shown to correlate with later developmental outcomes. However, the environment of the neonatal intensive care unit (NICU) has changed since the NBRS and NRE were first validated, and it is not known whether they are still able to accurately predict future developmental outcomes. The objective of this study was therefore to examine the ability of the NBRS and NRE, both alone and in combination with socio-economic variables, to predict future developmental outcomes in the contemporary NICU. The subjects were 219 neonates of less than 32 weeks' gestational age discharged from the NICU between November 2001 and December 2006 who had undergone both the NBRS and NRE. Infants were assessed at chronological age 6, 12 and 24 months, with developmental quotients being assigned at these ages. Parental socio-economic data were also collected and analysed. The hypothesis was that the NBRS and NRE would be less effective at predicting neurodevelopmental outcomes in the contemporary NICU. The best measure of future developmental outcome is likely to need to include both neurobiological and socio-economic risk factors.
To determine the association of genetic variants in known age-related macular degeneration (AMD) risk-associated genes with outcome of anti-vascular endothelial growth factor (VEGF) treatment in ...neovascular AMD.
Prospective cohort study.
We enrolled 224 consecutive patients with neovascular AMD at the Royal Victorian Eye and Ear Hospital, Australia.
Patients were treated with 3 initial monthly ranibizumab or bevacizumab injections followed by 9 months of "as required" injections based on clinician's decision at each follow-up visit according to retreatment criteria. Seventeen single nucleotide polymorphisms (SNPs) in known AMD risk-associated genes including CFH (rs800292, rs3766404, rs1061170, rs2274700 and rs393955), HTRA1 (rs11200638), CFHR1-5 (rs10922153, rs16840639, rs6667243, and rs1853883), LOC387715/ARMS2 (rs3793917 and rs10490924), C3 (rs2230199 and rs1047286), C2 (rs547154), CFB (rs641153) and F13B (rs6003) were examined. Multivariate analysis was used to determine the role of each SNP in treatment outcome.
The influence of selected SNPs on mean change in visual acuity (VA) at 12 months.
Mean baseline VA was 51 ± 16.8 Early Treatment Diabetic Retinopathy Study letters. Overall, the mean change in VA from baseline was +3.2 ± 14.9 letters at 12 months. The AA (homozygote risk) genotype at rs11200638 - HTRA1 promoter SNP (P = 0.001) and GG (homozygote risk) genotype at rs10490924 (A69S) in LOC387715/ARMS2 (P = 0.002) were each significantly associated with poorer VA outcome at 12 months after multiple correction. Mean ± standard deviation change in VA from baseline in patients with AA genotype at rs11200638 was -2.9 ± 15.2 letters after 12 months compared with +5.1 ± 14.1 letters in patients with AG or GG genotypes at this SNP. Patients with either of these genotypes were also significantly more likely to lose >15 letters after 12 months. SNPs rs11200638 and rs10490924 were in high linkage disequilibrium (r(2) = 0.92). None of the other examined SNPs was associated with outcome.
The HTRA1 promoter SNP (rs11200638) and A69S at LOC387715/ARMS2 were associated with a poorer visual outcome for ranibizumab or bevacizumab treatment in neovascular AMD, suggesting strong pharmacogenetic associations with anti-VEGF treatment. This finding could aid in applying more individualized treatment regimens based on patients' genotype to achieve optimal treatment response in AMD.
The authors have no proprietary or commercial interest in any materials discussed in this article.
To determine the association of genetic variants of the VEGFA gene with outcome of anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (AMD).
A ...prospective cohort study.
We included 201 consecutive patients receiving anti-VEGF injections for neovascular AMD.
Patients were followed over 12 months. They were treated with 3 initial monthly ranibizumab or bevacizumab injections. Thereafter, the decision to retreat was made by clinicians at each follow-up visit on the basis of retreatment criteria. Seven tagged single nucleotide polymorphisms (tSNPs) in the VEGFA gene were selected and examined. Multivariate data analysis was used to determine the role of each tSNP in treatment outcome.
The influence of selected VEGFA tSNPs on visual acuity (VA) outcome at 6 months.
Mean baseline VA was 51±17 Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores. Overall, the mean change in VA from baseline was +6.5±12, +4.4±13.4, and +2.3±14.6 letters at 3, 6, and 12 months, respectively. The tSNP rs3025000 was the only SNP significantly associated (P<1 × 10(-4)) with visual outcome at 6 months with multiple correction. The presence of the T allele (TC or TT genotypes) at this tSNP predicted a better outcome of +7 letters at 6 months compared with the CC genotype. In a subgroup analysis, presence of the T allele predicted a significantly higher chance of the patients belonging to the responder group (gain of ≥5 letters from baseline) after 3, 6, and 12 months treatment (odds ratio, 2.7, 3.5, and 2.4; 95% confidence interval, 1.46-5.07, 1.82-6.71, and 1.27-4.57, respectively) than any other outcome group.
Pharmacogenetic association with anti-VEGF treatments may influence the visual outcomes in neovascular AMD. In patients with the T allele in tSNP rs3025000, there was a significantly better visual outcome at 6 months and a greater chance of the patients belonging to the responder group with anti-VEGF treatment at 3, 6, and 12 months. The VA outcomes of patients harboring the T allele at SNP rs3025000 were comparable with those of the pivotal clinical trials but with fewer injections, making the treatment perhaps more cost effective in certain subgroups of patients.
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
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