Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children

Summary

Background

Children often starve for longer than recommended by current preoperative fasting guidelines.

Aims

We studied the effects of implementing a more lenient fasting regimen on the duration of clear fluid fasting, as well as the incidence of extended fasting in children.

Methods

Preoperative duration of clear fluid fasting was recorded for patients scheduled for procedures in a unit applying the standard 6-4-2 fasting regimen. This group was compared with a cohort in the same unit 1 year after transitioning to a 6-4-0 fasting regimen. The latter includes no limitations on clear fluid intake until the child is called to theater. A third cohort from a unit in which the 6-4-0 fasting regimen has been implemented for over a decade was also studied for comparison.

Results

Patients fasting according to the 6-4-2 fasting regimen (n = 66) had a median fasting time for clear fluids of 4.0 h and a 33.3% incidence of fasting more than 6 h. After transitioning to the 6-4-0 fasting regimen (n = 64), median duration of fasting for clear fluids decreased to 1.0 h, and the incidence of fasting more than 6 h decreased to 6.3%. In the second unit (n = 73), median fasting time was 2.2 h and the proportion of patients fasting more than 6 h was 21.9%.

Conclusion

The introduction and implementation of the 6-4-0 fasting regimen reduces median fluid fasting duration and the number of children subjected to extended fasting.

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Biallelic mutations in NALCN: Expanding the genotypic and phenotypic spectra of IHPRF1

Loss-of function mutations in NALCN on chromosome 13q, a sodium leak channel that maintains baseline neuronal excitability, cause infantile hypotonia with psychomotor retardation and characteristic faces 1 (IHPRF1, OMIM #615419). Here, we document two individuals with early onset hypotonia with poor feeding and intellectual disability who were compatible with a diagnosis of IHPRF1. The two patients had bi-allelic mutations in NALCN through two different genetic mechanisms: Patient 1 had bi-allelic splice site mutations, that is c.1267-2A>G, derived from heterozygous parents, while Patient 2 had a partial maternal uniparental isodisomy that harbored a frameshift mutation, that is c.2022_2023delAT, in chromosome 13 that was detected through a dedicated algorithm for homozygosity data mapping in whole exome sequencing. The delineation of the exact pattern of inheritance provided vital information regarding the risk of recurrence. In animal models with Nalcn mutations, two behavioral phenotypes, that are, postnatal dyspnea and sleep disturbance, have been reported. Our observations of the two patients with postnatal dyspnea and one patient with sleep disturbance support an association between these two behavioral phenotypes and NALCN mutations in humans. The routine use of a detection algorithm for homozygosity data mapping might improve the diagnostic yields of next-generation sequencing.

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Novel STRA6 null mutations in the original family described with Matthew–Wood syndrome

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Single suture craniosynostosis: Identification of rare variants in genes associated with syndromic forms

We report RNA-Sequencing results on a cohort of patients with single suture craniosynostosis and demonstrate significant enrichment of heterozygous, rare, and damaging variants among key craniosynostosis-related genes. Genetic burden analysis identified a significant increase in damaging variants in ATR, EFNA4, ERF, MEGF8, SCARF2, and TGFBR2. Of 391 participants, 15% were found to have damaging and potentially causal variants in 29 genes. We observed transmission in 96% of the affected individuals, and thus penetrance, epigenetics, and oligogenic factors need to be considered when recommending genetic testing in patients with nonsyndromic craniosynostosis.

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Congenital limb deficiencies and major associated anomalies in Alberta for the years 1980–2012

There is a wide range of the proportion of congenital anomalies associated with limb deficiencies reported in the literature. This variation is primarily attributed to methodology and classification differences. The distribution of associated anomalies among cases with congenital limb deficiencies in Alberta born between January 1, 1980 and December 31, 2012 is described. Of the 170 cases identified, most were live born (75.3%), male (61.8%), had longitudinal limb deficiencies (78.8%), and had associated anomalies outside the musculoskeletal system (77.6%). Significant associations between the preaxial longitudinal group and the central nervous, gastrointestinal, and cardiovascular systems are reported as well as between the postaxial longitudinal group and congenital hip and foot anomalies. Probable and possible syndrome diagnoses are described for cases with recognized malformation patterns.

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Interdependent feedback regulation of breathing by the carotid bodies and the retrotrapezoid nucleus

Abstract

The retrotrapezoid nucleus, RTN, regulates breathing in a CO₂ and state-dependent manner. RTN neurons are glutamatergic and innervate principally the respiratory pattern generator; they regulate multiple aspects of breathing, including active expiration, and maintain breathing automaticity during non-REM sleep. RTN neurons encode arterial PCO₂ /pH via cell-autonomous and paracrine mechanisms, and via input from other CO₂-responsive neurons. In short, RTN neurons are a pivotal structure for breathing automaticity and arterial PCO₂ homeostasis.

The carotid bodies stimulate the respiratory pattern generator directly and, indirectly, by activating RTN via a neuronal projection originating within the solitary tract nucleus. The indirect pathway operates under normo- or hypercapnic conditions; under respiratory alkalosis (e.g. hypoxia) RTN neurons are silent and the excitatory input from the carotid bodies is suppressed. Also, silencing RTN neurons optogenetically quickly triggers a compensatory increase in carotid body activity. Thus, in conscious mammals, breathing is subject to a dual and interdependent feedback regulation by chemoreceptors. Depending on the circumstance, the activity of the carotid bodies and that of RTN vary in the same or the opposite direction, producing additive or countervailing effects on breathing. These interactions are mediated either via changes in blood gases or by brainstem neuronal connections but their ultimate effect is invariably to minimize arterial PCO₂ fluctuations.

We discuss the potential relevance of this dual chemoreceptor feedback to cardiorespiratory abnormalities present in diseases in which the carotid bodies are hyperactive at rest, e.g. essential hypertension, obstructive sleep apnea and heart failure.

This article is protected by copyright. All rights reserved

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Direct Testing for Allele-Specific Expression Differences Between Conditions

Allelic imbalance (AI) indicates the presence of functional variation in cis regulatory regions. Detecting cis regulatory differences using AI is widespread, yet there is no formal statistical methodology that tests whether AI differs between conditions. Here we present a novel model and formally test differences in AI across conditions using Bayesian credible intervals. The approach tests AI by environment (GxE) interactions and can be used to test AI between environments, genotypes, sex, and any other condition. We incorporate bias into the modeling process. Bias is allowed to vary between conditions, making the formulation of the model general. As gene expression affects power for detection of AI, and as expression may vary between conditions, the model explicitly takes coverage into account. The proposed model has low type I and II error under several scenarios, and is robust to large differences in coverage between conditions. We reanalyze RNA-seq data from a Drosophila melanogaster population panel, with F1 genotypes, to compare levels of AI between mated and virgin female flies and we show that AI*genotype interactions can also be tested. To demonstrate the use of the model to test genetic differences and interactions, a formal test between two F1's was performed, showing the expected 20% difference in AI. The proposed model allows a formal test of GxE and GxG and reaffirms a previous finding, that cis regulation is robust between environments.

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