Profiling gut microbiota and bile acid metabolism in critically ill children.

Broad-spectrum antimicrobial use during the treatment of critical illness influences gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary to secondary bile acids. We previously observed reduced fermentation capacity in the faecal microbiota of critically ill children upon hospital admission. Here, we further explore the timecourse of the relationship between the microbiome and bile acid profile in faecal samples collected from critically ill children. The microbiome was assayed by sequencing of the 16S rRNA gene, and faecal water bile acids were measured by liquid chromatography mass spectrometry. In comparison to admission faecal samples, members of the Lachnospiraceae recovered during the late-acute phase (days 8-10) of hospitalisation. Patients with infections had a lower proportion of Lachnospiraceae in their gut microbiota than controls and patients with primary admitting diagnoses. Keystone species linked to ecological recovery were observed to decline with the length of PICU admission. These species were further suppressed in patients with systemic infection, respiratory failure, and undergoing surgery. Bile acid composition recovers quickly after intervention for critical illness which may be aided by the compositional shift in Lachnospiraceae. Our findings suggest gut microbiota recovery can be readily assessed via measurement of faecal bile acids.

Predicting use of high-flow nasal cannula therapy following extubation in paediatrics.

BACKGROUND: High-flow nasal cannula (HFNC) therapy is widely used for respiratory support within paediatrics, most commonly used as a supportive measure in acute respiratory failure, aiming to avoid invasive mechanical ventilation (IMV). It is increasingly being used following extubation of critically ill children potentially at a higher risk of requiring re-intubation. Less data indicate the use for post-extubation HFNC therapy or possible clinical outcomes of this therapy. AIMS AND OBJECTIVES: To identify reasons for, and variables to predict, the use of HFNC therapy post-extubation. DESIGN: This was a retrospective case-control study. METHODS: All children admitted to a nine-bedded regional paediatric intensive care unit requiring IMV between 18 December 2017 and 28 November 2018 were identified. The demographic data and bedside clinical and laboratory variables of the patients requiring HFNC therapy were compared with those who did not require HFNC. RESULTS: There was no statistical difference in the median age and weight of children receiving HFNC therapy post-extubation compared with children not receiving it. In a logistic regression model, the highest ventilation (peak inspiratory pressure) and oxygen requirements in the first 24 hours of admission, along with the presence of comorbidity and use of HFNC therapy prior to intubation, predicted the use of HFNC following extubation, (r2 0.42, area under the receiver operating curve 0.843, P < .0001). CONCLUSIONS: The direct correlation between high initial ventilatory requirements and pre-existing comorbidity was significant for the use of post-extubation HFNC therapy. This may be useful to stratify children in the use of HFNC therapy post-extubation in the critically ill population. RELEVANCE TO CLINICAL PRACTICE: This study provides evidence that it may be possible to predict the use of HFNC therapy post-extubation. Avoiding unnecessary use of this therapy improves patient care while providing a positive economic impact.

Corpus callosum and inferior forebrain white matter microstructure are related to functional outcome from raised intracranial pressure in child traumatic brain injury.

In severe paediatric traumatic brain injury (TBI), a common focus of treatment is raised intracranial pressure (ICP). We have previously reported frontal cerebral vulnerability with executive deficits from raised ICP in paediatric TBI. Now, using diffusion tensor imaging (DTI) in a different population, we have examined fractional anisotropy (FA), and mean, axial and radial diffusivity (MD, AD, RD) in 4 regions of the corpus callosum (CC) and in both inferior frontal regions. Our aim was to examine during the chronic phase of TBI whether the CC cross-sectional area correlated with regional DTI metrics of white matter microstructure, with global outcome ratings of function (Functional Independence Measure and Multiattribute Health Status Classification) and with performance in the Rey-Osterrieth Complex Figure (ROCF) test. We examined 33 paediatric TBI cases who were followed, on average, 4.9 years after severe injury. All cases had received mechanical ventilation during their acute treatment and, a priori, they were assigned to a non-ICP or a raised ICP group. Twenty-two participants had mainly right-sided injury at the time of acute ictus. The findings confirm that severe TBI in childhood, complicated by intracranial hypertension, results in CC vulnerability. In the chronic phase of recovery, it is reduced in the cross-sectional area, it is more compact and thinned, and the anterior region is disproportionately small. Late after raised ICP, we have also found that individuals exhibit regional microstructural abnormality with combined reduced FA and increased MD, AD and RD. Smaller size and such microstructural changes in the anterior CC were associated with similar right-sided (rather than left-sided) frontal microstructural changes in the ICP group. Taken together, this evidence points to an interaction between raised ICP-related brain tissue perturbation and focal frontal extracallosal injury, leading to anterior CC regional vulnerability, most likely wallerian degeneration. At long-term follow-up, this lack of white matter integrity in the anterior CC is correlated with functional outcome, particularly in aspects of social interaction and the copy component of the ROCF test, which suggests that the CC-to-forebrain function warrants further study in chronic TBI.

Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency.

OBJECTIVE: Untreated GH-deficient adults are predisposed to insulin resistance and excess cardiovascular mortality. We showed previously that short-term treatment with a very low GH dose (LGH) enhanced insulin sensitivity in young healthy adults. The present study was therefore designed to explore the hypothesis that LGH, in contrast to the standard GH dose titrated to normalize serum IGF-I levels (SGH), may have differing effects on insulin sensitivity, body composition, and cardiovascular risk markers [lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and adiponectin] in adults with severe GH deficiency. PATIENTS AND METHODS: In this 12-month open, prospective study, 25 GH-deficient adults were randomized to receive either a fixed LGH (0.10 mg/day, n = 13) or SGH (mean dose 0.48 mg/day, n = 12), and eight age- and body mass index (BMI)-matched GH-deficient adults acted as untreated controls. Fasting blood samples were collected at baseline and at months 1, 3, 6, 9 and 12. Assessments of insulin sensitivity, using the hyperinsulinaemic euglycaemic clamp technique, and body composition, using dual-energy X-ray absorptiometry, were performed at baseline and at month 12. RESULTS: The LGH decreased fasting glucose levels (P < 0.01) and enhanced insulin sensitivity (P < 0.02), but body composition, nonesterified fatty acid (NEFA) levels and cardiovascular risk markers were unchanged. The SGH did not modify insulin sensitivity, decreased truncal fat mass (P < 0.05), CRP (P < 0.05) and IL-6 (P < 0.05) levels, and increased NEFA levels (P < 0.05). No changes were observed with the untreated controls. CONCLUSION: Our data indicate that, in contrast to the SGH, fixed administration of the LGH enhances insulin sensitivity with no apparent effects on body composition, lipolysis and other surrogate cardiovascular risk markers in adults with severe GH deficiency. Thus, the LGH may potentially be a beneficial replacement dose in reducing type 2 diabetes risk in adults with severe GH deficiency.

The neuroendocrine stress response and severity of acute respiratory syncytial virus bronchiolitis in infancy.

OBJECTIVE: Neuroendocrine hormones have profound effects on the immune system. The immune response is a major factor in the pathogenesis of acute respiratory syncytial virus (RSV) infection. We hypothesised that there is a relationship between the neuroendocrine response in acute RSV infection, the severity of illness, and the degree of lymphopenia. DESIGN: Prospective, non-randomised cohort study of infants hospitalised for RSV infection requiring mechanical ventilation or managed conservatively. The study assessed the effect of age, gender, birth gestation, and severity of illness on stress hormone profile and its relationship to lymphocyte count. SETTING: Regional Paediatric Intensive Care Unit (PICU) and children's wards. PATIENTS: Thirty-two consecutive infants with RSV infection were enrolled, of which thirteen were mechanically ventilated on PICU (study subjects) and nineteen treated on the ward (comparison group). Twenty-three children (72%) returned for follow-up. MEASUREMENTS AND MAIN RESULTS: A specific neuroendocrine profile was found in PICU patients compared to ward patients (Wilks Lambda = 0.36, F = 9.05, P =.03). PICU patients had significantly higher prolactin and growth hormone, and significantly lower leptin and IGF-1. Cortisol levels were the same. PICU patients were more lymphopenic compared to ward patients (P =.0001). On multiple regression analysis, prolactin and leptin levels accounted for 57% of the variation in lymphocyte count. CONCLUSIONS: Whereas the effect of intensive care (mechanical ventilation and medication) could not be controlled for, our results suggest that there is an association between the neuroendocrine hormone response, severity of illness and degree of lymphopenia.

Evaluation of ventilatory efficiency during exercise in patients with idiopathic scoliosis undergoing spinal fusion.

STUDY DESIGN: A prospective evaluation of ventilatory function following spinal fusion in adolescent idiopathic scoliosis. OBJECTIVES: To prospectively evaluate pulmonary function, maximal oxygen uptake, and ventilatory efficiency during exercise in patients with adolescent idiopathic scoliosis before surgery and a minimum of 2 years postoperation. SUMMARY OF BACKGROUND DATA: For reasons that are unclear, patients with untreated adolescent idiopathic scoliosis tend to avoid aerobic exercise. Their reluctance may be the result of low ventilatory efficiency, as they often approach their ventilatory ceiling at maximum oxygen uptake despite forced vital capacities that are near normal. This inefficiency of ventilation with exercise may explain the reluctance of patients with scoliosis to pursue aerobic fitness. No study has evaluated the effect spinal fusion has on the ventilatory function of patients with scoliosis during exercise. METHODS: Forty-two patients with adolescent idiopathic scoliosis (36 female and 6 male) at an average age of 14 +/- 3 years (range 10-18 years) underwent spinal fusion. Twenty patients underwent a posterior spinal fusion alone, 20 an anterior spinal fusion alone, and 2 an anterior spinal fusion and posterior spinal fusion. The average Cobb measurement was 55 degrees (range 40-85 degrees). Pulmonary function values (forced vital capacity, total lung capacity, maximum voluntary ventilation), maximum oxygen uptake (VO2max), and ventilatory efficiency were obtained before surgery and a minimum of 2 years postoperation. RESULTS: For all patients, forced vital capacity percent predicted decreased from 88.1% to 81.4% (P < 0.0001). Total lung capacity also declined from 90.5% to 88.5% but was not statistically significant (P = 0.189). Percent predicted maximum oxygen uptake (VO2max) declined from 93.6% to 85.1% (P = 0.00029). Ventilatory efficiency, as measured by VEmax/maximum voluntary ventilation, improved from 0.76 to 0.68 (P = 0.005), whereas measured by VEmax/FEV1 x 40 was unchanged from 0.69 to 0.70 (P = 0.172) postoperation. The choice of operative approach [anterior (n = 20) versus posterior (n = 20)] or whether rib graft was harvested (n = 33) versus iliac crest graft (n = 7) did not change these results. CONCLUSION: Improvement in ventilatory efficiency during exercise does not occur in the majority of patients with adolescent idiopathic scoliosis following spinal fusion and thus cannot be relied on to foster increases in aerobic activity.