Explore the vast range of titles available.

Why did you do this work?The climate crisis is a global emergency that disproportionately affects children and young people. The RCPCH’s climate change action plan calls on paediatricians to be role models in mitigating climate change personally and professionally.1 Road transport is the largest contributor to UK CO2 emissions, with average car commuters (33km round-trip) directly emitting 1.1 metric tonnes of CO2 annually (MTCO2e).2 3 Understanding the environmental cost of commuting for paediatric training is crucial for exploring mitigation strategies. Given that rotational training placements are often outside trainees’ control and assigned on short notice—making green commuting options like carpooling challenging—this study aimed to estimate the CO2 emissions associated with commuting for paediatric rotational training in the East of England (EoE).What did you do?An anonymous electronic survey was distributed to all EoE paediatric trainees in June 2024, with reminders given at regional study days. The survey collected data on commuting modality currently and to furthest rotational placement, home outcodes, LTFT status, and concern for environment and ranked factors influencing commuting choices. Commute distances were calculated using RStudio’s ‘gmapsdistance’ package, and CO2 emissions were derived from UK government data.4 5 Annual emissions were based on 20 round trips per month, adjusted for full-time equivalent (FTE) status over 12 months. Total emissions for all trainees were calculated as a sum of mean emissions per trainee stratified by number of trainees per level of training.What did you find?Of 225 EoE Paediatric trainees, 34% (n=77) responded. Individual car use, mostly fossil-fuelled, is the dominant mode of commuting among trainees. Despite concerns about environmental impact, commute choices were primarily influenced by time, caring responsibilities, and cost and least by environmental concerns. The mean daily round-trip commute to current placements was 84.7km (UK average: 33km), and to furthest placements 141km. Annually, trainees averaged 8,968km commuting to current placements, equivalent to 1.94MTCO2e, and 14,641km to their furthest placements, equivalent to 3.4MTCO2e. Extrapolating these figures to all EoE paediatric trainees estimates 435.8MTCO2e attributable to paediatric training annually.What does it mean?Paediatric rotational training generates significant CO2 emissions, primarily from car commuting. Trainees are concerned about the environmental impact, but cost, time, and caring responsibilities primarily influence their commute choices. As paediatricians, we must reflect on the necessity of frequent rotations and their environmental impact. The RCPCH should consider strategies to alleviate this and lead by example: promoting remote training opportunities, improved longitudinal rota design and facilitating or incentivising green transport options including transition to electric vehicles. These initiatives would reflect the College’s commitment to sustainability, environmental responsibility, and trainee wellbeing.ReferencesThe impact of climate change on global child health – position statement RCPCH. Available from: https://www.rcpch.ac.uk/resources/impact-climate-change-global-child-health-position-statement#key-messages-for-health-professionalsOffice for National Statistics. Available from: https://www.ons.gov.uk/visualisations/dvc99999/covid-emissions-gh-pages/index.html?2020 UK Greenhouse Gas Emissions. Available from: https://www.ipcc-nggip.iges.or.jp/public/wetlands/index.html;UK Government – Department for Energy Security and Net Zero. Greenhouse gas reporting: conversion factors 2023. Available from: https://www.gov.uk/government/publications/greenhouse-gas-reporting-conversion-factors-2023Melo R, Zarruk D. Distance and travel time between two points from google maps. 2016.

ObjectiveReports of hyperinsulinism typically focus on infants managed by highly specialised services. However, neonates with hyperinsulinism are initially managed by neonatologists and often not referred to specialists. This study aimed to characterise the diversity in presentation and management of these infants.SettingLevel 3 neonatal intensive care.PatientsNeonates with hyperinsulinism, defined as blood glucose <2.8 mmol/mL and insulin level >6 pmol/L.Design7-year retrospective study (January 2015–December 2021).Results99 cases were identified: severe—treated with diazoxide (20%), moderate—clinically concerning hyperinsulinism not treated with diazoxide (30%), mild—biochemical hyperinsulinism (50%). Birth weight z-score was −1.02±2.30 (mean±SD), 42% were preterm, but neither variable correlated with clinical severity. The severe group received a higher concentration of intravenous glucose (27±12%) compared with the moderate (15±7%) and mild (16±10%) groups (p<0.001). At diagnosis, the intravenous glucose intake was similar in the severe (7.43±5.95 mg/kg/min) and moderate (5.09±3.86 mg/kg/min) groups, but higher compared with the mild group (3.05+/2.21 mg/kg/min) (p<0.001). In the severe group, term infants started diazoxide earlier (9.9±4.3 days) compared with preterm (37±26 days) (p=0.002). The national congenital hyperinsulinism service was consulted for 23% of infants, and 3% were transferred.ConclusionsThis study highlights the diversity in clinical presentation, severity and prognosis of neonatal hyperinsulinism, irrespective of birth weight and gestational age. More infants were small rather than large for gestational age, and the majority had transient hyperinsulinism and were not referred to the national centre, or treated with diazoxide. Further research is required to understand the breadth of neonatal hyperinsulinism and optimal management.

ObjectivesHypoglycaemia is a common finding in the newborn and may be associated with hyperinsulinism (HI). Congenital HI is a rare cause of neonatal hypoglycaemia and is associated with severe neurodevelopmental impairment.1 Previous reports on neonatal HI focus on congenital HI rather than the more commonly presenting transient HI. The primary objective of this study is to describe a cohort of neonates with hyperinsulinism from a neonatal, rather than a supra-specialist perspective.MethodsWe conducted a service evaluation of the management of neonatal hyperinsulinism in a level 3 Neonatal Intensive Care Unit, over seven years (1/2015 – 12/2021). We collected demographic data, maternal health details, information regarding clinical care, associated conditions and follow-up. The cohort was subdivided into subgroups based on clinical severity, gestational age and growth. Clinical severity was defined as:(1) Severe: treated with diazoxide,(2) Moderately severe: clinically worrying HI without diazoxide,(3) Mild: biochemical evidence of HI without clinically worrying criteria.Results99 cases identified – Severe(n=20), Moderately-severe(n=30), Mild(n=49).77% were born locally. Hypoglycaemia was the primary reason for admission in 58% of locally born and 30% of transferred from other hospitals. 12% of infants were Large for gestational age (LGA), 35% Small for Gestational Age (SGA), 42% preterm (<37 weeks), and 17% had diabetic mothers. Birthweight z-score, gestational age, and maternal diabetes did not influence clinical severity.When exploring subgroups of clinical severity, age on diagnosis was lower in Mild infants, compared to Severe (p=0.008). Length of admission was longer for Severe and Moderate compared to Mild(p<0.001). Severe infants received a higher maximum strength of dextrose compared to Moderate and Mild(p<0.001). Glucose requirement on diagnosis was higher in Severe(9.0 ± 5.0mg/kg/min) and Moderate(7.4 ± 3.6mg/kg/min), compared to Mild (5.3 ± 2.3mg/kg/min)(p<0.001).Severe infants had not established full enteral feeds when started on diazoxide, with a mean glucose requirement of 13.2±4.8mg/kg/min. The Severe group achieved full enteral feeds on day 26±15, significantly later than the Moderate group (11±7, p<0.0001).ConclusionThis study highlights the diversity of infants with HI cared for in the NICU. SGA, LGA and preterm infants may be at increased risk from both HI and limited availability of alternative fuels.2 Management of HI is challenging, as the decision to treat with diazoxide is not straightforward and is influenced by multiple objective and subjective variables. Further research is needed into larger cohorts from different centres to explore the range of clinical practice, and long-term outcomes of this diverse group of infants.ReferencesMartino, Sartorelli, Gragnaniello, Burlina. Congenital hyperinsulinism in clinical practice: from biochemical pathophysiology to new monitoring techniques, 23 September 2022.Stanley, Thornton, De Leon. New approaches to screening and management of neonatal hypoglycemia based on improved understanding of the molecular mechanism of hypoglycemia, 10 March 2023.

The BRCA Challenge is a long-term data-sharing project initiated within the Global Alliance for Genomics and Health (GA4GH) to aggregate BRCA1 and BRCA2 data to support highly collaborative research activities. Its goal is to generate an informed and current understanding of the impact of genetic variation on cancer risk across the iconic cancer predisposition genes, BRCA1 and BRCA2. Initially, reported variants in BRCA1 and BRCA2 available from public databases were integrated into a single, newly created site, www.brcaexchange.org. The purpose of the BRCA Exchange is to provide the community with a reliable and easily accessible record of variants interpreted for a high-penetrance phenotype. More than 20,000 variants have been aggregated, three times the number found in the next-largest public database at the project's outset, of which approximately 7,250 have expert classifications. The data set is based on shared information from existing clinical databases-Breast Cancer Information Core (BIC), ClinVar, and the Leiden Open Variation Database (LOVD)-as well as population databases, all linked to a single point of access. The BRCA Challenge has brought together the existing international Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium expert panel, along with expert clinicians, diagnosticians, researchers, and database providers, all with a common goal of advancing our understanding of BRCA1 and BRCA2 variation. Ongoing work includes direct contact with national centers with access to BRCA1 and BRCA2 diagnostic data to encourage data sharing, development of methods suitable for extraction of genetic variation at the level of individual laboratory reports, and engagement with participant communities to enable a more comprehensive understanding of the clinical significance of genetic variation in BRCA1 and BRCA2.

ObjectivesTo quantify the economic and psychological impact of the cancellation of operations due to winter pressures on patients, their families and the economy.DesignThis questionnaire study was designed with the help of patient groups. Data were collected on the economic and financial burden of cancellations. Emotions were also quantified on a 5-point Likert scale.SettingFive NHS Hospital Trusts in the East Midlands region of England.ParticipantsWe identified 796 participants who had their elective operations cancelled between 1 November 2017 and 31 March 2018 and received responses from 339 (43%) participants.InterventionsParticipants were posted a modified version of a validated quality of life questionnaire with a prepaid return envelope.Main outcome measuresThe primary outcome measures were the financial and psychological impact of the cancellation of elective surgery on patients and their families.ResultsOf the 339 respondents, 163 (48%) were aged <65 years, with 111 (68%) being in employment. Sixty-six (19%) participants had their operations cancelled on the day. Only 69 (62%) of working adults were able to return to work during the time scheduled for their operation, with a mean loss of 5 working days (SD 10). Additional working days were lost subsequently by 60 (54%) participants (mean 7 days (SD 10)). Family members of 111 (33%) participants required additional time off work (mean 5 days (SD 7)). Over 30% of participants reported extreme levels of sadness, disappointment, anger, frustration and stress. At least moderate concern about continued symptoms was reported by 234 (70%) participants, and 193 (59%) participants reported at least moderate concern about their deteriorating condition.ConclusionsThe cancellation of elective surgery during the winter had an adverse impact on patients and the economy, including days of work lost and health-related anxiety. We recommend better planning, and provision of more notice and better support to patients.

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1 1000 Genomes Project data, we assessed associations of 11 11 11 11 million genetic variants with EOC risk from 1 15,437 cases unselected for family history and 30,845 controls and from 1 15,252 BRCA1 mutation carriers and 8,211 11 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 1 17q1111.2 (ATAD5) were associated with EOC risk, and at 1 1p34.3 (RSPO1) and 6p22.1 1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 1 10−8. Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

Summary Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point. Introduction Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome. Methods VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry. Results Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3–17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2–15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), −0.5 ± 1.1; p  = 0.001) and at 3 months (−0.6 ± 1.1; p  < 0.001), but not at 6 months (−0.3 ± 1.3; p  = 0.066) or 12 months (−0.3 ± 1.2; p  = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p  = 0.003). A subgroup ( N  = 16; 25 %) had LS BMD Z-scores that were ≤−1.0 at 12 months. In these children, each additional 1,000 mg/m 2 of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, −0.71 to −0.07; p  = 0.017). Conclusions The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤−1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.

Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r 2  > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer ( P  < 10 -7 ). Four of these contain plausible causative genes ( FGFR2 , TNRC9 , MAP3K1 and LSP1 ). At the second stage, 1,792 SNPs were significant at the P  < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach. Novel breast cancer genes Until the genome-wide association study on page 1087 was published online, known susceptibility genes — such as BRCA1 and BRCA2 — accounted for less than 25% of the familial risk of breast cancer. The new study, which involved 21,860 patients and 22,578 controls, has identified four genes positively associated with genetic susceptibility to breast cancer ( FGFR2 , TNRC9 , MAP3K1 and LSP1 ). Most previously identified breast cancer susceptibility genes are involved in DNA repair, but the newly discovered associations appear to relate more to the control of cell growth or to cell signalling. Only one of the genes — FGFR2 — had a clear prior relevance to breast cancer. The identification of these genes opens up new avenues of research into the causes of breast cancer. They may also become part of a new strategy to classify women's risk, paving the way for better disease prevention. Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.

PURPOSE : To evaluate the association between a previously published 313 variant–based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. METHODS : We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. RESULTS : For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06–1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR= 1.15, 95% CI (1.07–1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. CONCLUSION : The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decisionmaking.