ItemFetal manipulation of maternal metabolism is a critical function of the imprinted Igf2 gene(Cell Press, 2023-07-01) Lopez-Tello, J.; Yong, H. E. J.; Sandovici, I.; Dowsett, G. K. C.; Christoforou, E. R.; Salazar-Petres, E.; Boyland, R.; Napso, T.; Yeo, G. S. H.; Lam, B. Y. H.; Constancia, M.; Sferruzzi-Perri, A. N.Maternal-offspring interactions in mammals involve both cooperation and conflict. The fetus has evolved ways to manipulate maternal physiology to enhance placental nutrient transfer, but the mechanisms involved remain unclear. The imprinted Igf2 gene is highly expressed in murine placental endocrine cells. Here, we show that Igf2 deletion in these cells impairs placental endocrine signaling to the mother, without affecting placental morphology. Igf2 controls placental hormone production, including prolactins, and is crucial to establish pregnancy-related insulin resistance and to partition nutrients to the fetus. Consequently, fetuses lacking placental endocrine Igf2 are growth restricted and hypoglycemic. Mechanistically, Igf2 controls protein synthesis and cellular energy homeostasis, actions dependent on the placental endocrine cell type. Igf2 loss also has additional long-lasting effects on offspring metabolism in adulthood. Our study provides compelling evidence for an intrinsic fetal manipulation system operating in placenta that modifies maternal metabolism and fetal resource allocation, with long-term consequences for offspring metabolic health. ItemAlbumin versus balanced crystalloid for resuscitation in the treatment of sepsis: A protocol for a randomised controlled feasibility study, ABC-Sepsis""(Sage, 2023-02-01) Cafferkey, J.; Ferguson, A.; Grahamslaw, J.; Oatey, K.; Norrie, J.; Lone, N.; Walsh, T.; Horner, D.; Appelboam, A.; Hall, P.; Skipworth, R.; Bell, D.; Rooney, K.; Shankar-Hari, M.; Corfield, A.; Gray, A.BACKGROUND: Patients presenting with suspected sepsis to secondary care often require fluid resuscitation to correct hypovolaemia and/or septic shock. Existing evidence signals, but does not demonstrate, a benefit for regimes including albumin over balanced crystalloid alone. However, interventions may be started too late, missing a critical resuscitation window. METHODS: ABC Sepsis is a currently recruiting randomised controlled feasibility trial comparing 5% human albumin solution (HAS) with balanced crystalloid for fluid resuscitation in patients with suspected sepsis. This multicentre trial is recruiting adult patients within 12 hours of presentation to secondary care with suspected community acquired sepsis, with a National Early Warning Score ≥5, who require intravenous fluid resuscitation. Participants are randomised to 5% HAS or balanced crystalloid as the sole resuscitation fluid for the first 6 hours. OBJECTIVES: Primary objectives are feasibility of recruitment to the study and 30-day mortality between groups. Secondary objectives include in-hospital and 90-day mortality, adherence to trial protocol, quality of life measurement and secondary care costs. DISCUSSION: This trial aims to determine the feasibility of conducting a trial to address the current uncertainty around optimal fluid resuscitation of patients with suspected sepsis. Understanding the feasibility of delivering a definitive study will be dependent on how the study team are able to negotiate clinician choice, Emergency Department pressures and participant acceptability, as well as whether any clinical signal of benefit is detected. ItemCritical care drowning admissions in Southwest England 2009-2020, a retrospective study(Sage, 2023-02-01) Brayne, A. B.; Jones, W.; Lee, A.; Chatfield-Ball, C.; Kaye, D.; Ball, M.; Sacher, G.; Morgan, P.AIM: In the United Kingdom (UK), 600 deaths per annum are attributable to drowning. Despite this there is scarce critical care data on drowning patients globally. We describe drowning cases admitted to critical care units with a focus on functional outcomes. MATERIALS AND METHODS: Medical records for critical care admissions following a drowning event were retrospectively reviewed across six hospitals in Southwest England for cases presenting in the period between 2009 and 2020. Data was collected according to the Utstein international consensus guidelines on drowning. RESULTS: Forty-nine patients were included, 36 males and 13 females, including seven children. Median submersion duration was 2.5 min 20 cases were in cardiac arrest when rescued. At discharge 22 patients had preserved functional status, 10 patients had a reduced functional status. 17 patients died in hospital. CONCLUSION: Admission to critical care following drowning is uncommon and associated with high rates of mortality and poor functional outcomes. We find that 31% of those who survived a drowning event subsequently required an increased level of assistance with their activities of daily living. ItemPrevalence of skin pressure injury in critical care patients in the UK: results of a single-day point prevalence evaluation in adult critically ill patients(BMJ, 2022-11-23) Rubulotta, F.; Brett, S.; Boulanger, C.; Blackwood, B.; Deschepper, M.; Labeau, S. O.; Blot, S.OBJECTIVES: Hospital-acquired pressure injuries (PIs) are a source of morbidity and mortality, and many are potentially preventable. DESIGN: This study prospectively evaluated the prevalence and the associated factors of PIs in adult critical care patients admitted to intensive care units (ICU) in the UK. SETTING: This service evaluation was part of a larger, international, single-day point prevalence study of PIs in adult ICU patients. Training was provided to healthcare givers using an electronic platform to ensure standardised recognition and staging of PIs across all sites. PARTICIPANTS: The characteristics of the ICUs were recorded before the survey; deidentified patient data were collected using a case report form and uploaded onto a secure online platform. PRIMARY AND SECONDARY OUTCOME MEASURES: Factors associated with ICU-acquired PIs in the UK were analysed descriptively and using mixed multiple logistic regression analysis. RESULTS: Data from 1312 adult patients admitted to 94 UK ICUs were collected. The proportion of individuals with at least one PI was 16% (211 out of 1312 patients), of whom 8.8% (n=115/1312) acquired one or more PIs in the ICU and 7.3% (n=96/1312) prior to ICU admission. The total number of PIs was 311, of which 148 (47.6%) were acquired in the ICU. The location of majority of these PIs was the sacral area, followed by the heels. Braden score and prior length of ICU stay were associated with PI development. CONCLUSIONS: The prevalence and the stage of severity of PIs were generally low in adult critically ill patients admitted to participating UK ICUs during the study period. However, PIs are a problem in an important minority of patients. Lower Braden score and longer length of ICU stay were associated with the development of injuries; most ICUs assess risk using tools which do not account for this. TRIAL REGISTRATION NUMBER: NCT03270345.