A.S.P.E.N. Clinical Guidelines

Background: Children with severe intestinal failure and prolonged dependence on parenteral nutrition are susceptible to the development of parenteral nutrition–associated liver disease (PNALD). The purpose of this clinical guideline is to develop recommendations for the care of children with PN‐dependent intestinal failure that have the potential to prevent PNALD or improve its treatment. Method: A systematic review of the best available evidence to answer a series of questions regarding clinical management of children with intestinal failure receiving parenteral or enteral nutrition was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the American Society for Parenteral and Enteral Nutrition Board of Directors. Questions: (1) Is ethanol lock effective in preventing bloodstream infection and catheter removal in children at risk of PNALD? (2) What fat emulsion strategies can be used in pediatric patients with intestinal failure to reduce the risk of or treat PNALD? (3) Can enteral ursodeoxycholic acid improve the treatment of PNALD in pediatric patients with intestinal failure? (4) Are PNALD outcomes improved when patients are managed by a multidisciplinary intestinal rehabilitation team?     

Nitrite and Nitrate Concentrations and Metabolism in Breast Milk,Infant Formula,and Parenteral Nutrition

Dietary nitrate and nitrite are sources of gastric NO, which modulates blood flow, mucus production, and microbial flora. However, the intake and importance of these anions in infants is largely unknown. Nitrate and nitrite levels were measured in breast milk of mothers of preterm and term infants, infant formulas, and parenteral nutrition. Nitrite metabolism in breast milk was measured after freeze‐thawing, at different temperatures, varying oxygen tensions, and after inhibition of potential nitrite‐metabolizing enzymes. Nitrite concentrations averaged 0.07 ± 0.01 μM in milk of mothers of preterm infants, less than that of term infants (0.13 ± 0.02 μM) (P < .01). Nitrate concentrations averaged 13.6 ± 3.7 μM and 12.7 ± 4.9 μM, respectively. Nitrite and nitrate concentrations in infant formulas varied from undetectable to many‐fold more than breast milk. Concentrations in parenteral nutrition were equivalent to or lower than those of breast milk. Freeze‐thawing decreased nitrite concentration ~64%, falling with a half‐life of 32 minutes at 37°C. The disappearance of nitrite was oxygen‐dependent and prevented by ferricyanide and 3 inhibitors of lactoperoxidase. Nitrite concentrations in breast milk decrease with storage and freeze‐thawing, a decline likely mediated by lactoperoxidase. Compared to adults, infants ingest relatively little nitrite and nitrate, which may be of importance in the modulation of blood flow and the bacterial flora of the infant GI tract, especially given the protective effects of swallowed nitrite.     

Bladder neck contracture

Bladder neck contracture (BNC) is a well-described complication of the surgical treatment of benign and malignant prostate conditions. Nevertheless, etiologies of BNC development are highly dependent on the primary treatment modality undertaken with BNC also occurring after pelvic radiation. The treatment options for BNC can range from simple, office-based dilation procedures to more invasive, complex abdomino-perineal reconstructive surgery. Although numerous strategies have been described, a patient-specific approach is usually necessary in the management of these complex patients. In this review, we highlight various therapeutic maneuvers described for the management of BNC and further delineate a tailored approach utilized at our institution in these complicated patients.     

A Sequence of events model of episodic memory shows parallels in rats and humans

A critical feature of episodic memory is the ability to remember the order of events as they occurred in time, a capacity shared across species including humans, nonhuman primates, and rodents. Accumulating evidence suggests that this capacity depends on a network of structures including the hippocampus and the prefrontal cortex, but their respective contributions remain poorly understood. As addressing this important issue will require converging evidence from complementary investigative techniques, we developed a cross‐species, nonspatial sequence memory task suitable for behavioral and neurophysiological studies in rodents and in humans. The task involves the repeated presentation of sequences of items (odors in rats and images in humans) and requires subjects to make a judgment as to whether each item is presented “in sequence” or “out of sequence.” To shed light on the cognitive processes and sequence representations supporting performance, different types of “out of sequence” probe trials were used including: (i) repeating an item from earlier in the sequence (Repeats; e.g., ABA D), (ii) skipping ahead in the sequence (Skips; e.g., ABD ), and (iii) inserting an item from a different sequence into the same ordinal position (Ordinal Transfers; e.g., A2 CD). We found a remarkable similarity in the performance of rats and humans, particularly in the pattern of results across probe trial types. Thus, the results suggest that rats and humans not only remember the sequences of events, but also use similar underlying cognitive processes and mnemonic representations. This strong cross‐species correspondence validates this task for use in future basic and clinical interdisciplinary studies aimed at examining the neural mechanisms underlying episodic memory. © 2014 Wiley Periodicals, Inc.     

Differential developmental trajectories of magnetic susceptibility in human brain gray and white matter over the lifespan

As indicated by several recent studies, magnetic susceptibility of the brain is influenced mainly by myelin in the white matter and by iron deposits in the deep nuclei. Myelination and iron deposition in the brain evolve both spatially and temporally. This evolution reflects an important characteristic of normal brain development and ageing. In this study, we assessed the changes of regional susceptibility in the human brain in vivo by examining the developmental and ageing process from 1 to 83 years of age. The evolution of magnetic susceptibility over this lifespan was found to display differential trajectories between the gray and the white matter. In both cortical and subcortical white matter, an initial decrease followed by a subsequent increase in magnetic susceptibility was observed, which could be fitted by a Poisson curve. In the gray matter, including the cortical gray matter and the iron‐rich deep nuclei, magnetic susceptibility displayed a monotonic increase that can be described by an exponential growth. The rate of change varied according to functional and anatomical regions of the brain. For the brain nuclei, the age‐related changes of susceptibility were in good agreement with the findings from R2^* measurement. Our results suggest that magnetic susceptibility may provide valuable information regarding the spatial and temporal patterns of brain myelination and iron deposition during brain maturation and ageing. Hum Brain Mapp 35:2698–2713, 2014. © 2013 Wiley Periodicals, Inc .     

Paternal age of schizophrenia probands and endophenotypic differences from unaffected siblings

We evaluated the discrepancy of endophenotypic performance between probands with schizophrenia and unaffected siblings by paternal age at proband birth, a possible marker for de novo mutations. Pairs of schizophrenia probands and unaffected siblings (N=220 pairs) were evaluated on 11 neuropsychological or neurophysiological endophenotypes previously identified as heritable. For each endophenotype, the sibling-minus-proband differences were transformed to standardized scores. Then for each pair, the average discrepancy was calculated from its standardized scores. We tested the hypothesis that the discrepancy is associated with paternal age, controlling for the number of endophenotypes shared between proband and his or her sibling, and proband age, which were both associated with paternal age. The non-significant association between the discrepancy and paternal age was in the opposite direction from the hypothesis. Of the 11 endophenotypes only sensori-motor dexterity was significant, but in the opposite direction. Eight other endophenotypes were also in the opposite direction, but not significant. The results did not support the hypothesized association of increased differences between sibling/proband pairs with greater paternal age. A possible explanation is that the identification of heritable endophenotypes was based on samples for which schizophrenia was attributable to inherited rather than de novo/non-inherited causes.     

Safety of a quadrivalent meningococcal serogroups A,C, W and Y conjugate vaccine (MenACWY-CRM) administered with routine infant vaccinations: Results of an open-label,randomized, phase 3b controlled study in healthy infants

Background

The highest risk for invasive meningococcal disease (IMD) is in infants aged <1 year. Quadrivalent meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A, C, W and Y. This phase 3b, multinational, open-label, randomized, parallel-group, multicenter study evaluated the safety of a 4-dose series of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, concomitantly administered with routine vaccinations to healthy infants.

Methods

Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2, 4, 6 and 12 months. Adverse events (AEs) that were medically attended and serious adverse events (SAEs) were collected from all subjects from enrollment through 18 months of age. In a subset, detailed safety data (local and systemic solicited reactions and all AEs) were collected for 7 days post vaccination. The primary objective was a non-inferiority comparison of the percentages of subjects with ≥1 severe systemic reaction during Days 1–7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone (criterion: upper limit of 95% confidence interval [CI] of group difference <6%).

Results

A total of 7744 subjects were randomized with 1898 in the detailed safety arm. The percentage of subjects with severe systemic reactions was 16% after MenACWY-CRM plus routine vaccines and 13% after routine vaccines alone (group difference 3.0% (95% CI −0.8, 6.4%). Although the non-inferiority criterion was not met, post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone (group difference −0.1% [95% CI −4.9%, 4.7%]). Rates of solicited AEs, medically attended AEs, and SAEs were similar across groups.

Conclusion

In a large multinational safety study, a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable with a similar safety profile to routine vaccines given alone.