Paediatric intensive care admissions of preterm children born <32 weeks gestation: a national retrospective cohort study using data linkage

Objective: Survival of babies born very preterm (<32 weeks gestational age) has increased, although preterm-born children may have ongoing morbidity. We aimed to investigate the risk of admission to paediatric intensive care units (PICUs) of children born very preterm following discharge home from neonatal care. Design: Retrospective cohort study, using data linkage of National Neonatal Research Database and the Paediatric Intensive Care Audit Network datasets. Setting: All neonatal units and PICUs in England and Wales. Patients: Children born very preterm between 1 January 2013 and 31 December 2018 and admitted to neonatal units. Main outcome measures: Admission to PICU after discharge home from neonatal care, before 2 years of age. Results: Of the 40 690 children discharged home from neonatal care, there were 2308 children (5.7%) with at least one admission to PICU after discharge. Of these children, there were 1901 whose first PICU admission after discharge was unplanned. The percentage of children with unplanned PICU admission varied by gestation, from 10.2% of children born <24 weeks to 3.3% born at 31 weeks. Following adjustment, unplanned PICU admission was associated with lower gestation, male sex (adjusted OR (aOR) 0.79), bronchopulmonary dysplasia (aOR 1.37), necrotising enterocolitis requiring surgery (aOR 1.39) and brain injury (aOR 1.42). For each week of increased gestation, the aOR was 0.90. Conclusions: Most babies born <32 weeks and discharged home from neonatal care do not require PICU admission in the first 2 years. The odds of unplanned admissions to PICU were greater in the most preterm and those with significant neonatal morbidity. Data availability statement: Data may be obtained from a third party and are not publicly available. Data may be obtained from a third party and are not publicly available. PICANet data may be requested from the data controller, the Healthcare Quality Improvement Partnership (HQIP). A Data Access Request Form can be obtained from https://www.hqip.org.uk/national-programmes/accessing-ncapop-data/%23.XQeml_lKhjU

Impact of prematurity on long-stay paediatric intensive care unit admissions in England 2008-2018

BACKGROUND: Survival following extreme preterm birth has improved, potentially increasing the number of children with ongoing morbidity requiring intensive care in childhood. Previous single-centre studies have suggested that long-stay admissions in paediatric intensive care units (PICUs) are increasing. We aimed to examine trends in long-stay admissions (≥28 days) to PICUs in England, outcomes for this group (including mortality and PICU readmission), and to determine the contribution of preterm-born children to the long-stay population, in children aged <2 years. METHODS: Data was obtained from the Paediatric Intensive Care Audit Network (PICANet) for all children <2 years admitted to National Health Service PICUs from 1/1/2008 to 31/12/2018 in England. We performed descriptive analysis of child characteristics and PICU outcomes. RESULTS: There were 99,057 admissions from 67,615 children. 2,693 children (4.0%) had 3,127 long-stays. Between 2008 and 2018 the annual number of long-stay admissions increased from 225 (2.7%) to 355 (4.0%), and the proportion of bed days in PICUs occupied by long-stay admissions increased from 24.2% to 33.2%. Of children with long-stays, 33.5% were born preterm, 53.5% were born at term, and 13.1% had missing data for gestational age. A considerable proportion of long-stay children required PICU readmission before two years of age (76.3% for preterm-born children). Observed mortality during any admission was also disproportionately greater for long-stay children (26.5% for term-born, 24.8% for preterm-born) than the overall rate (6.3%). CONCLUSIONS: Long-stays accounted for an increasing proportion of PICU activity in England between 2008 and 2018. Children born preterm were over-represented in the long-stay population compared to the national preterm birth rate (8%). These results have significant implications for future research into paediatric morbidity, and for planning future PICU service provision

Post-bronchoscopy fatal endobronchial hemorrhage in a woman with bronchopulmonary mucormycosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>During infection, Mucorales fungi invade major blood vessels, leading to extensive necrosis, and in cases of extensive pulmonary disease, bleeding into the lungs may occur.</p> <p>Case presentation</p> <p>We report an unexpected event of post-bronchoscopy fatal endobronchial hemorrhage in a 62-year-old HIV-negative Italian woman with well controlled diabetes mellitus who presented with diffuse cavitated pulmonary lesions. Fiberoptic bronchoscopy revealed bilateral obstruction of the segmental bronchi. Fatal massive bleeding occurred after standard biopsy procedures. Histologic examination showed that the hyphae were more deeply colored by hematoxylin-eosin (H&E) than by other stains for fungi. Culture and autopsy confirmed bronchopulmonary mucormycosis.</p> <p>Conclusion</p> <p>Infection by Mucorales fungi should be considered in the diabetes population regardless of the degree of metabolic control. In these patients, particular caution should be taken during bronchoscopic procedures because of the greater friability of the fungal lesions.</p

Cardiovascular, endocrine and behavioural responses to suckling and permanent separation in goats

<p>Abstract</p> <p>Background</p> <p>Suckling can be a peaceful or vulnerable event for goats and kids, whereas, separation is suggested as stressful. The aim of this study was to investigate physiology and behaviour in these two different situations in dairy goats.</p> <p>Methods</p> <p>Four studies were performed with seven goats kept with their first-born kid in individual boxes. The goats were videotaped and heart rate and arterial blood pressure were recorded every minute by telemetry from parturition until 24 hours after separation. One to two days after parturition, Study 1 was performed with analyses of heart rate and blood pressure around a suckling. In Study 2, performed 3-5 days after parturition, blood sampling was done before, during and after suckling. Study 3 was performed 4-6 days post partum, with blood sampling before and after a permanent goat and kid separation. In addition, vocalisations were recorded after separation. Blood samples were obtained from a jugular vein catheter and analysed for plasma cortisol, β-endorphin, oxytocin, and vasopressin concentrations. Study 4 was performed during the first (N1) and second nights (N2) after parturition and the nights after Study 2 (N3) and 3 (N4). Heart rate, blood pressure and time spent lying down were recorded.</p> <p>Results</p> <p>The kids suckled 2 ± 0.2 times per hour and each suckling bout lasted 43 ± 15 s. In Study 1, heart rate and blood pressure did not change significantly during undisturbed suckling. In Study 2, plasma cortisol (P ≤ 0.05 during suckling and P ≤ 0.01 five minutes after suckling) and β-endorphin (P ≤ 0.05) concentrations increased during suckling, but oxytocin and vasopressin concentrations did not change. In Study 3, the goats and kids vocalised intensively during the first 20 minutes after separation, but the physiological variables were not affected. In Study 4, heart rate and arterial blood pressure declined gradually after parturition and were lowest during N4 (P ≤ 0.05) when the goats spent longer time lying down than during earlier nights (P ≤ 0.01 during N1 and N3 and P ≤ 0.05 during N2).</p> <p>Conclusions</p> <p>Suckling elevated plasma cortisol and β-endorphin concentrations in the goats. The intensive vocalisation in the goats after separation, earlier suggested to indicate stress, was not accompanied by cardiovascular or endocrine responses.</p

Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function

Neurodegenerative disorders are associated with impaired cognitive function and worse physical health outcomes. This study aims to test whether polygenic risk for Alzheimer’s disease, Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) is associated with cognitive function and physical health in the UK Biobank, a cohort of healthy individuals. Group-based analyses were then performed to compare the top and bottom 10% for the three neurodegenerative polygenic risk scores; these groups were compared on the cognitive and physical health variables. Higher polygenic risk for AD, ALS, and FTD was associated with lower cognitive performance. Higher polygenic risk for FTD was also associated with increased forced expiratory volume in 1s and peak expiratory flow. A significant group difference was observed on the symbol digit substitution task between individuals with high polygenic risk for FTD and high polygenic risk for ALS. The results suggest some overlap between polygenic risk for neurodegenerative disorders, cognitive function and physical health

Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (<i>N</i>=112 151) and 24 GWAS consortia

Causes of the well-documented association between low levels of cognitive functioning and many adverse neuropsychiatric outcomes, poorer physical health and earlier death remain unknown. We used linkage disequilibrium regression and polygenic profile scoring to test for shared genetic aetiology between cognitive functions and neuropsychiatric disorders and physical health. Using information provided by many published genome-wide association study consortia, we created polygenic profile scores for 24 vascular–metabolic, neuropsychiatric, physiological–anthropometric and cognitive traits in the participants of UK Biobank, a very large population-based sample (N=112 151). Pleiotropy between cognitive and health traits was quantified by deriving genetic correlations using summary genome-wide association study statistics and to the method of linkage disequilibrium score regression. Substantial and significant genetic correlations were observed between cognitive test scores in the UK Biobank sample and many of the mental and physical health-related traits and disorders assessed here. In addition, highly significant associations were observed between the cognitive test scores in the UK Biobank sample and many polygenic profile scores, including coronary artery disease, stroke, Alzheimer’s disease, schizophrenia, autism, major depressive disorder, body mass index, intracranial volume, infant head circumference and childhood cognitive ability. Where disease diagnosis was available for UK Biobank participants, we were able to show that these results were not confounded by those who had the relevant disease. These findings indicate that a substantial level of pleiotropy exists between cognitive abilities and many human mental and physical health disorders and traits and that it can be used to predict phenotypic variance across samples

Low Frequency and Variability of FLT3 Mutations in Korean Patients with Acute Myeloid Leukemia

FLT3 mutations are common genetic changes, and are reported to have prognostic significance in acute myeloid leukemia (AML). The FLT3 internal tandem duplication (ITD) and the D835 activating mutation in the tyrosine kinase domain (TKD) were analyzed by polymerase chain reaction (PCR) in the genomic DNA of Korean patients with AML at diagnosis and during follow-up. There were 226 patients with AML enrolled between March 1996 and August 2005. The incidence of ITD and TKD at diagnosis was 13% (29/226) and 3% (6/226). When compared to Western and other Asian patients with AML, Korean patients had a lower frequency by about two-thirds of ITD and TKD. Among the non-M3 cases (N=203), the patients with an ITD had a significantly shorter event-free survival when compared with those without an ITD (p=0.0079). Among 54 relapsed patients, 9 patients had the FLT3 ITD at diagnosis. Six patients demonstrated a reappearance of the ITD and 3 patients remained negative at relapse. One patient, among 45 patients who relapsed, had a negative baseline ITD but acquired a de novo ITD at relapse. There were 101 samples from 93 patients in remission; they were all negative for an ITD. Among 34 patients who failed to achieve a remission, five patients had a persistent ITD and one patient had a de novo ITD. These results support the concept of resistance of FLT3 ITD leukemic clones to chemotherapy. Therefore, effective therapy with FLT3 targeting agents may improve the prognosis of non-M3 AML patients with the FLT3 mutation

A Role for Phosphatidic Acid in the Formation of “Supersized” Lipid Droplets

Lipid droplets (LDs) are important cellular organelles that govern the storage and turnover of lipids. Little is known about how the size of LDs is controlled, although LDs of diverse sizes have been observed in different tissues and under different (patho)physiological conditions. Recent studies have indicated that the size of LDs may influence adipogenesis, the rate of lipolysis and the oxidation of fatty acids. Here, a genome-wide screen identifies ten yeast mutants producing “supersized” LDs that are up to 50 times the volume of those in wild-type cells. The mutated genes include: FLD1, which encodes a homologue of mammalian seipin; five genes (CDS1, INO2, INO4, CHO2, and OPI3) that are known to regulate phospholipid metabolism; two genes (CKB1 and CKB2) encoding subunits of the casein kinase 2; and two genes (MRPS35 and RTC2) of unknown function. Biochemical and genetic analyses reveal that a common feature of these mutants is an increase in the level of cellular phosphatidic acid (PA). Results from in vivo and in vitro analyses indicate that PA may facilitate the coalescence of contacting LDs, resulting in the formation of “supersized” LDs. In summary, our results provide important insights into how the size of LDs is determined and identify novel gene products that regulate phospholipid metabolism