Neonatal sulfur amino acid metabolism

At birth, infants can be classified either by gestational age (GA) or by weight. Neonates born < 37 weeks are classified as preterm, < 28 weeks as very preterm and < 26 weeks as extremely preterm infants. Prematurely born infants can also be classified by birth weight as follows (1): - Low birth weight (LBW) < 2500 g - Very low birth weight (VLBW) < 1500 g - Extremely low birth weight (ELBW) < 1000 g However, both classifications are used arbitrary in the clinical setting and obviously the infant born very prematurely has most likely a birth weight < 1500 g. Over the past 25 years life support in the neonate born prematurely has improved tremendously and has created major advantages in medical treatment possibilities and survival. Nowadays it is generally accepted to treat the very preterm infant and even the extremely preterm infant since survival rates for these infants are still increasing

Retrospective cohort study on factors associated with mortality in high-risk pediatric critical care patients in the Netherlands

Background: High-risk patients in the pediatric intensive care unit (PICU) contribute substantially to PICU-mortality. Complex chronic conditions (CCCs) are associated with death. However, it is unknown whether CCCs also increase mortality in the high-risk PICU-patient. The objective of this study is to determine if CCCs or other factors are associated with mortality in this group. Methods: Retrospective cohort study from a national PICU-database (2006-2012, n = 30,778). High-risk PICU-patients, defined as patients 30% according to either the recalibrated Pediatric Risk of Mortality-II (PRISM) or the Paediatric Index of Mortality 2 (PIM2), were included. Patients with a cardiac arrest before PICU-admission were excluded. Results: In total, 492 high-risk PICU patients with mean predicted risk of 24.8% (SD 22.8%) according to recalibrated PIM2 and 40.0% (SD 23.8%) according to recalibrated PRISM were included of which 39.6% died. No association was found between CCCs and non-survival (odds ratio 0.99; 95% CI 0.62-1.59). Higher Glasgow coma scale at PICU admission was associated with lower mortality (odds ratio 0.91; 95% CI 0.87-0.96). Conclusio

Imaging sublingual microcirculatory perfusion in pediatric patients receiving procedural sedation with propofol: A pilot study

Objective: Procedural sedation with propofol is widely used in the pediatric population. A well-known side effect of propofol is a decrease in peripheral vascular resistance resulting in hypotension, but little is known about the effects on microcirculation in humans. We aimed to evaluate the effects of propofol on the sublingual microcirculatory perfusion by continuous video imaging in pediatric patients undergoing procedural sedation. Methods: Patients admitted to the Pediatric Intensive Care Unit for procedural sedation were recruited. Oral microcirculation was measured employing a continuous monitoring strategy with incident dark-field illumination imaging. Measurements were obtained before and 3 minutes after propofol induction. Total and perfused vessel densities, proportion of perfused vessels, microvascular flow index, blood vessel diameter (Øbv), and systemic hemodynamics were analyzed. Results: Continuous measurements were achieved in seven patients. Three minutes after propofol induction mean arterial pressure decreased (P = 0.028) and total and perfused vessel densities increased by 12% (P = 0.018) and 16% (P = 0.018), respectively. MFI was unaltered and mean Øbv increased but not significantly. Conclusions: Propofol induction induces a reduction in mean arterial pressure and a rise in sublingual microvascular perfusion. The observed effects of propofol on the sublingual microcirculation may be due to a decrease in microvascular resistance

Development of entrustable professional activities for paediatric intensive care fellows: A national modified Delphi study

Contains fulltext : 232752.pdf (Publisher’s version ) (Open Access)Entrustable professional activities (EPAs), as a focus of learner assessment, are supported by validity evidence. An EPA is a unit of professional practice requiring proficiency in multiple competencies simultaneously, that can be entrusted to a sufficiently competent learner. Taken collectively, a set of EPAs define and inform the curriculum of a specialty training. The goal of this study was to develop a set of EPAs for Dutch PICU fellows. A multistage methodology was employed incorporating sequential input from task force members, a medical education expert, PICU fellowship program directors, and PICU physicians and fellows via a modified three-round Delphi study. In the first modified Delphi round, experts rated indispensability and clarity of preliminary EPAs. In the subsequent rounds, aggregated scores for each EPA and group comments were provided. In round two, respondents rated indispensability and clarity of revised EPAs. Round three was used to gain explicit confirmation of suitability to implement these EPAs. Based on median ratings and content validity index (CVI) analysis for indispensability in the first two rounds, all nine preliminary EPAs covered activities that were deemed essential to the clinical practice of PICU physicians. Based on median ratings and CVI analysis for clarity however, four EPAs needed revision. With an agreement percentage of 93-100% for all individual EPAs as well as the set as a whole, a high degree of consensus among experts was reached in the third round. The resulting nine PICU EPAs provide a succinct overview of the core tasks of Dutch PICU physicians. These EPAs were created as an essential first step towards developing an assessment system for PICU fellows, grounded in core professional activities. The robust methodology used, may have broad applicability for other (sub)specialty training programs aiming to develop specialty specific EPAs

Development of entrustable professional activities for paediatric intensive care fellows: A national modified Delphi study

Entrustable professional activities (EPAs), as a focus of learner assessment, are supported by validity evidence. An EPA is a unit of professional practice requiring proficiency in multiple competencies simultaneously, that can be entrusted to a sufficiently competent learner. Taken collectively, a set of EPAs define and inform the curriculum of a specialty training. The goal of this study was to develop a set of EPAs for Dutch PICU fellows. A multistage methodology was employed incorporating sequential input from task force members, a medical education expert, PICU fellowship program directors, and PICU physicians and fellows via a modified three-round Delphi study. In the first modified Delphi round, experts rated indispensability and clarity of preliminary EPAs. In the subsequent rounds, aggregated scores for each EPA and group comments were provided. In round two, respondents rated indispensability and clarity of revised EPAs. Round three was used to gain explicit confirmation of suitability to implement these EPAs. Based on median ratings and content validity index (CVI) analysis for indispensability in the first two rounds, all nine preliminary EPAs covered activities that were deemed essential to the clinical practice of PICU physicians. Based on median ratings and CVI analysis for clarity however, four EPAs needed revision. With an agreement percentage of 93-100% for all individual EPAs as well as the set as a whole, a high degree of consensus among experts was reached in the third round. The resulting nine PICU EPAs provide a succinct overview of the core tasks of Dutch PICU physicians. These EPAs were created as an essential first step towards developing an assessment system for PICU fellows, grounded in core professional activities. The robust methodology used, may have broad applicability for other (sub)specialty training programs aiming to develop specialty specific EPAs

Methionine transmethylation and transsulfuration in the piglet gastrointestinal tract

Methionine is an indispensable sulfur amino acid that functions as a key precursor for the synthesis of homocysteine and cysteine. Studies in adult humans suggest that splanchnic tissues convert dietary methionine to homocysteine and cysteine by means of transmethylation and transsulfuration, respectively. Studies in piglets show that significant metabolism of dietary indispensable amino acids occurs in the gastrointestinal tissues (GIT), yet the metabolic fate of methionine in GIT is unknown. We show here that 20% of the dietary methionine intake is metabolized by the GIT in piglets implanted with portal and arterial catheters and fed milk formula. Based on analyses from intraduodenal and intravenous infusions of [1-13C]methionine and [2H3]methionine, we found that the whole-body methionine transmethylation and remethylation rates were significantly higher during duodenal than intravenous tracer infusion. First-pass splanchnic metabolism accounted for 18% and 43% of the whole-body transmethylation and remethylation, respectively. Significant transmethylation and transsulfuration was demonstrated in the GIT, representing \xe2\x89\x8827% and \xe2\x89\x8823% of whole-body fluxes, respectively. The methionine used by the GIT was metabolized into homocysteine (31%), CO2(40%), or tissue protein (29%). Cystathionine \xce\xb2-synthase mRNA and activity was present in multiple GITs, including intestinal epithelial cells, but was significantly lower than liver. We conclude that the GIT consumes 20% of the dietary methionine and is a significant site of net homocysteine production. Moreover, the GITs represent a significant site of whole-body transmethylation and transsulfuration, and these two pathways account for a majority of methionine used by the GITs

Cyst(e)ine requirements in enterally fed very low birth weight preterm infants

OBJECTIVE. Optimal nutrition is of utmost importance for the preterm infant's later health and developmental outcome. Amino acid requirements for preterm infants differ from those for term and older Infants, because growth rates differ. Some nonessential amino acids, however, cannot be sufficiently synthesized endog-enously. Cyst(e)ine is supposed to be such a conditionally essential amino acid in preterm infants. The objective of this study was to determine, at 32 and 35 weeks' postmenstrual age, cyst(e)ine requirements in fully enterally fed very low birth weight preterm infants with gestational ages of <29 weeks. METHODS. Infants were randomly assigned to 1 of the 5 graded cystine test diets that contained generous amounts of methionine. Cyst(e)ine requirement was determined with the indicator amino acid oxidation technique ([I-13C]phenylaIanlne) after 24-hour adaptation. RESULTS.Fractional [I13-CJphenylalanine oxidation was established in 47 very low birth weight preterm infants (mean gestational age: 28 weeks ± 1 week SD; birth weight: 1.07 kg ± 0.21 kg SD). Increase in dietary cyst(e)ine intake did not result in a decrease in fractional [l-13,CJphenylalanine oxidation. CONCLUSIONS.These data do not support the hypothesis that endogenous cyst(e)ine synthesis is limited in very low birth weight preterm infants with gestational ages of <29 weeks, both at 32 and 35 weeks postmenstrual age. It is safe to conclude that cyst(e)ine requirement is <I8 mg/kg per day in enterally fed very low birth weight preterm infants who are older than 32 weeks' postmenstrual age and whose methionine intake is adequate. Therefore, cyst(e)ine is probably not a conditionally essential amino acid in these infants. Copyrigh

Amino acids for the neonate: Search for the ideal dietary composition

Amino acids play crucial roles as precursors for proteins and neurotransmitters, as transport molecules, and in cell signaling. In this review, we describe the unique functions of the individual amino acids and conclude that the amino acid requirements of parenterally fed neonates are inadequately defined. Parenterally fed neonates are at risk of amino acid deficiency or toxicity because the intestines serve as an important site of metabolism, regulating systemic availability of individual amino acids