Biomarkers of gut injury in neonates - where are we in predicting necrotising enterocolitis?

Despite advances in neonatal care Necrotising Enterocolitis (NEC) continues to have a significant mortality and morbidity rate, and with increasing survival of those more immature infants the population at risk of NEC is increasing. Ischaemia, reperfusion, and inflammation underpin diseases affecting intestinal blood flow causing gut injury including Necrotising Enterocolitis. There is increasing interest in tissue biomarkers of gut injury in neonates, particularly those representing changes in intestinal wall barrier and permeability, to determine whether these could be useful biomarkers of gut injury. This article reviews current and newly proposed markers of gut injury, the available literature evidence, recent advances and considers how effective they are in clinical practice. We discuss each biomarker in terms of its effectiveness in predicting NEC onset and diagnosis or predicting NEC severity and then those that will aid in surveillance and identifying those infants are greatest risk of developing NEC.

Could Near Infrared Spectroscopy (NIRS) be the new weapon in our fight against Necrotising Enterocolitis?

There is no ideal single gut tissue or inflammatory biomarker available to help to try and identify Necrotising Enterocolitis (NEC) before its clinical onset. Neonatologists are all too familiar with the devastating consequences of NEC, and despite many advances in neonatal care the mortality and morbidity associated with NEC remains significant. In this article we review Near Infrared Spectroscopy (NIRS) as a method of measuring regional gut tissue oxygenation. We discuss its current and potential future applications, including considering its effectiveness as a possible new weapon in the early identification of NEC.

Regional cerebral and splanchnic tissue oxygen saturation in preterm infants - Longitudinal normative measurements.

BACKGROUND: To investigate regional splanchnic and cerebral tissue oxygen saturation in preterm infants <30 weeks gestation. METHODS: Cerebral (cTOI) and splanchnic (sTOI) Tissue Oxygenation Index were measured weekly in 5 min epochs for a total period of 60 min using NIRS (NIRO-300) for the first 8 weeks of life, in 48 appropriately grown preterm infants born at <30 weeks gestation. Infants who developed HPI and/or NEC (n = 12) and those that died (n = 1) were excluded from our main outcome measure of regional gut and cerebral tissue oxygenation in healthy preterm infants <30 weeks gestation. RESULTS: Median birthweight 789 g (460-1486), gestational age 25+6 weeks (23+0-29+1) and 51.4% female. 217 NIRS measurements were completed across the first 8 weeks of life. Mean weekly cTOI ranged from 56.8-65.4% and sTOI ranged from 36.7-46.0%. Mean cTOI was significantly higher than mean sTOI (p < 0.001) throughout the first 8 weeks of life. Mean cTOI decreased significantly with increasing postnatal age [-0.59% each week (-1.26% to -0.07%) p = 0.04]. None of the examined confounding factors had a significant effect. CONCLUSIONS: This is the first report of regional cerebral and splanchnic tissue oxygen saturation ranges during the first 8 weeks of life for preterm infants born at <30 weeks gestation.

The National Collaborating Centre for Methods and Tools (NCCMT): Supporting evidence-informed decision-making in public health in Canada.

The National Collaborating Centre for Methods and Tools (NCCMT) is part of a network of six National Collaborating Centres for Public Health (NCC) created in 2005 by the federal government following the severe acute respiratory syndrome (SARS) epidemic to strengthen public health infrastructure in Canada. The work of the NCCMT, to support evidence-informed decision-making (EIDM) in public health in Canada, is accomplished by curating trustworthy evidence, building competence to use evidence and accelerating change in EIDM. Ongoing engagement with its target audiences ensures NCCMT's relevance and ability to respond to evolving public health needs. This has been particularly critical during the coronavirus disease 2019 (COVID-19) pandemic, which saw NCCMT pivot its activities to support the public health response by conducting rapid reviews on priority questions identified by decision-makers from federal to local levels as well as create and maintain a national repository of in-progress or completed syntheses. These efforts, along with partnering with the COVID-19 Evidence Network to support Decision-Making (COVID-END), sought to reduce duplication, increase coordination of synthesis efforts and support decision-makers to use the best available evidence in decision-making. Data from website statistics illustrate the successful uptake of these initiatives across Canada and internationally.

Hypertrophic cardiomyopathy in an extremely preterm infant.

We present a case of an extreme preterm infant (Baby X) born at 24-week gestation. The echocardiogram showed evidence of hypertrophic cardiomyopathy (HCM) and a patent ductus arteriosus (PDA). There are a number of well-known causes of neonatal HCM including genetic, metabolic and endocrine. PDA is commonly present in preterm infants, and this can contribute to cardiac remodelling and result in cardiac changes mimicking HCM. Furthermore, medications such as steroids can also cause HCM through various mechanisms. A careful consideration of all the different aetiologies for HCM is important for appropriate management of such cases. This report examines the evidence in the literature for the above differential diagnoses and highlights the challenges in diagnosing the underlying cause of HCM in a preterm infant.

Cerebral Oxygenation in Preterm Infants With Necrotizing Enterocolitis.

BACKGROUND AND OBJECTIVES: Preterm infants with necrotizing enterocolitis (NEC) are known to have worse neurodevelopmental outcomes, but there is no substantial evidence to support an underlying pathophysiology. We aimed to examine whether cerebral oxygenation differs in those infants who develop NEC compared to cerebral oxygenation in those who do not. METHODS: We examined 48 infants <30 weeks' gestation admitted to a tertiary level NICU from October 2016 to May 2018. Infants with birth weight less than or equal to the second percentile, abnormal antenatal dopplers or twin-to-twin-transfusion-syndrome were excluded. Cerebral oximetry measurements were performed by using a near-infrared spectroscopy (NIRS) monitor weekly for 60 minutes, allowing measurement of cerebral tissue oxygenation index from the first week of life to 36 weeks postconceptional age. Weekly clinical status was also recorded. NEC was defined as greater than or equal to Bell stage 2. RESULTS: The median birth weight was 884 g (range of 460-1600 g), the median weeks' gestational age was 26 + 3/7 (23 + 0/7 to 29 + 6/7), and 52% were girls. In total, 276 NIRS measurements were completed, and 7 infants developed NEC. NIRS measurements from 1 infant with NEC and 4 infants without NEC who developed hemorrhagic parenchymal infarcts were excluded from analysis. Infants who developed NEC had significantly lower cerebral tissue oxygenation index than those who did not (P = .011), even when adjusted for confounders, including gestational age, birth weight, patent ductus arteriosus, enteral feeds, sex, ethnicity, and hemoglobin. CONCLUSIONS: Infants with NEC have significantly lower cerebral tissue oxygenation throughout their neonatal intensive care stay in comparison with those who did not develop NEC. This is a novel finding and could explain their worse neurodevelopmental outcome.

Red Blood Cell Transfusion in Preterm Infants: Current Evidence and Controversies.

The current evidence regarding the indication, advantages and risks of red blood cell transfusion (RBCT) for preterm infants is discussed. This is an important area in Neonatology to be examined given that 90% of extremely low birth weight infants receive RBCT and many controversies remain regarding when to transfuse and the risks of RBCT. The various treatment thresholds and guidelines used are presented and we compare the short-term clinical benefits of liberal and restrictive RBCT in preterm infants; the majority of these are equivocal and sadly long-term outcome data is limited. The latest evidence on how anaemia and blood transfusion affect organ perfusion in preterm infants is presented. This is important when trying to establish the optimal trigger threshold for RBCT in preterm infants, especially because the knowledge about the adaptive physiological responses to anaemia in very low birth weight infants and the effects of RBCT at various levels of anaemia is also inadequate. Further research into the physiological adaptive response to anaemia of varying degrees and to RBCT at different levels of anaemia in preterm infants of different gestational and post-natal ages is needed before we can conclusively guide the optimal timing and trigger thresholds for RBCT in preterm infants.

The impact and efficacy of routine pulse oximetry screening for CHD in a local hospital.

OBJECTIVES: The objective of this study was to evaluate the impact and efficacy of pulse oximetry screening for CHD in a level-two neonatal unit without on-site access to paediatric echocardiography. METHODS: All neonatal unit admissions between 1 September, 2011 and 31 August, 2013 were reviewed to determine the outcomes of newborns identified by pulse oximetry screening. Record linkage with the National Congenital Heart Disease Audit allowed follow-up of newborns with a negative screening result. RESULTS: There were 11,233 live births during the study period, with 973 neonatal unit admissions unrelated to pulse oximetry screening. From the remaining screening population of 10,260 newborns, 23 were admitted on the basis of a screen-positive result; three of the 23 patients went on to have urgent echocardiograms, and two were found to have critical CHD. In the 21 newborns without critical CHD, an alternative diagnosis was made in 16 cases. Record linkage with the National Congenital Heart Disease Audit indicated that no newborns born in the hospital during the study period received surgery for critical CHD following negative screening. The estimated sensitivity of screening was 100% (95% confidence interval 15.81-100%) and specificity was 99.80% (95% confidence interval 99.69-99.87%), with a false-positive rate of 0.20% (95% confidence interval 0.13-0.31%). CONCLUSION: The introduction of pulse oximetry screening to a hospital where paediatric echocardiography services are not available is practical, results in very few referrals to the regional paediatric cardiology centre, and detects cases of CHD that would otherwise go undiagnosed. Record linkage with a national CHD database provides a straightforward method for tracking cases of CHD that may have been missed by screening.

A randomized trial of temazepam versus acetazolamide in high altitude sleep disturbance.

This study is the first comparative trial of sleep medications at high altitude. We performed a randomized, double-blind trial of temazepam and acetazolamide at an altitude of 3540 meters. 34 healthy trekkers with self-reports of high-altitude sleep disturbance were randomized to temazepam 7.5 mg or acetazolamide 125 mg taken at bedtime for one night. The primary outcome was sleep quality on a 100 mm visual analog scale. Additional measurements were obtained with actigraphy; pulse oximetry; and questionnaire evaluation of sleep, daytime drowsiness, daytime sleepiness, and acute mountain sickness. Sixteen subjects were randomized to temazepam and 18 to acetazolamide. Sleep quality on the 100 mm visual analog scale was higher for temazepam (59.6, SD 20.1) than acetazolamide (46.2, SD 20.2; p=0.048). Temazepam also demonstrated higher subjective sleep quality on the Groningen Sleep Quality Scale (3.5 vs. 6.8, p=0.009) and sleep depth visual analog scale (60.3 vs. 41.4, p=0.028). The acetazolamide group reported significantly more awakenings to urinate (1.8 vs. 0.5, p=0.007). No difference was found with regards to mean nocturnal oxygen saturation (84.1 vs. 84.4, p=0.57), proportion of the night spent in periodic breathing, relative desaturations, sleep onset latency, awakenings, wake after sleep onset, sleep efficiency, Stanford Sleepiness Scale scores, daytime drowsiness, or change in self-reported Lake Louise Acute Mountain Sickness scores. We conclude that, at current recommended dosing, treatment of high-altitude sleep disturbance with temazepam is associated with increased subjective sleep quality compared to acetazolamide.

Kawasaki disease: always straight to the heart?

Kawasaki disease is an important differential diagnosis when evaluating prolonged fever in childhood. Although the aetiology of this vasculitic disease process remains obscure, prompt recognition and treatment significantly reduces vascular complications such as coronary artery aneurysms. Patients presenting with atypical or incomplete diagnostic features remain a challenge. Here the authors describe the atypical features of Kawasaki disease that led to profound acute hearing loss in a 6-year-old boy with complex congenital heart disease. Coronary changes were not seen on early follow-up, but the patient required bilateral hearing aids. Considering Kawasaki disease early, even in the possibly confusing context of complex congenital heart disease and atypical symptomatology, is crucial to avoid long-term sequelae.

The views of doctors in their first year of medical practice on the lasting impact of a preparation for house officer course they undertook as final year medical students.

BACKGROUND: The UK General Medical Council recommends that medical students have the opportunity of shadowing the outgoing new doctor whose post they will soon undertake. At the University of Nottingham the two-week shadowing period was preceded by two weeks of lectures/seminars wherein students followed sessions on topics such as common medical/surgical emergencies, contracts, time management, surviving the first two years of clinical practice, careers advice and so on. The present study aimed to gain a better knowledge and understanding of the lasting impact of a four-week preparation course for new Foundation Year 1 doctors [F1 s - interns]. The objectives chosen to achieve this aim were: 1/ to determine the extent to which the lecture/seminar course and shadowing period achieved their stated aim of smoothing the transition from life as a medical student to work as a new doctor; 2/ to evaluate perceptions of the importance of various forms of knowledge in easing the transition between medical student and new doctor METHOD: In the spring of 2007, 90 graduates from Nottingham were randomly selected and then emailed a link to a short, online survey of quantitative and qualitative questions. Of these 76 responded. Analysis of quantitative data was carried out using SPSS 16.0 and employed McNemar's test. Analysis of the qualitative data was carried out using the constant comparative method. RESULTS: Only 31% of respondents strongly agreed or agreed that the lecture/seminar part of the course prepared them well for their first FY1 post; 14% agreed that during their first job they drew on the knowledge gained during the lecture/seminar course; 94% strongly agreed or agreed that the shadowing part of the course was more useful than the lecture/seminar part. Experiential knowledge gained in the shadowing was the most highly valued, followed by procedural knowledge with propositional knowledge coming far behind. CONCLUSIONS: Our study shows that new doctors retrospectively value most the knowledge they are able to transfer to the workplace and value least material which seems to repeat what they had learned for their final exams.