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Objective: To evaluate the association of donor sex with transfusion-associated recipient immune responses in preterm newborns receiving unwashed and washed blood., Design: A cohort study using data collected during the Effect of Washed versus Unwashed Packed Red Blood Cell Transfusion on Immune Responses in the Extremely Preterm Newborn randomised trial., Setting: Participants were recruited from two South Australian hospitals between September 2015 and December 2020., Patients: Preterm newborns (<29 weeks)., Interventions: Transfusion with unwashed and washed packed red blood cells (PRBCs) from either exclusively male or any female donor for the first three transfusions., Main Outcomes Measures: The primary outcome was the change from baseline in post-transfusion plasma cytokine concentrations, specifically interferon gamma, interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12, IL-17A and tumour necrosis factor (TNF)., Results: In total, 153 newborns were evaluated. By the third transfusion, the magnitude of pretransfusion to post-transfusion change in cytokines between the groups differed for IL-6 (p=0.003), IL-12 (p=0.008), IL-17A (p=0.003) and TNF (p=0.007). On post hoc comparison, compared with the unwashed-any female donor group, IL-6 (p<0.05), IL-12 (p<0.05) and IL-17A (p<0.01) were lower in the washed-exclusively male donor group, and IL-6 (p<0.01), IL-12 (p<0.05) and TNF (p<0.01) were lower in the washed-any female donor group., Conclusion: These findings suggest that transfusion with unwashed PRBCs from female donors is associated with an increased recipient immune response, an effect that can be ameliorated with pretransfusion washing. Larger randomised controlled studies confirming this mechanistic link between donor sex and transfusion-associated morbidity are warranted., Trial Registration Number: ACTRN12613000237785., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objective: Comprehensive data on the burden of severe acute pancreatitis (SAP) in global intensive care units (ICUs) and trends over time are lacking. Our objective was to compare trends in hospital and ICU mortality, in-hospital and ICU length of stay, and costs related to ICU admission in Australia and New Zealand (ANZ) for SAP., Methods: We performed a retrospective, observational, cohort study of ICU admissions reported to the ANZ Intensive Care Society Adult Patient Database over three consecutive six-year time periods from 2003 to 2020., Results: 12,635 patients with SAP from 189 ICUs in ANZ were analysed. No difference in adjusted hospital mortality (11.4% vs 11.5% vs 11.0%, p = 0.85) and ICU mortality rates (7.5% vs 8.0% vs 8.1%, p = 0.73) were noted over the study period. Median length of hospital admission reduced over time (13.9 days in 2003-08, 13.1 days in 2009-14 and 12.5 days in 2015-20; p < 0.01). No difference in length of ICU stay was noted over the study period (p = 0.13). The cost of managing SAP in ANZ ICUs remained constant over the three time periods., Conclusions: In critically-ill SAP patients in ANZ, no change in mortality has been noted over nearly two decades. There was a slight reduction in hospital stay (1 day), while the length of ICU stay remained unchanged. Given the significant costs related to care of patients with SAP in ICU, these findings highlight the need to prioritise resource allocation for healthcare delivery and targeted clinical research to identify treatments aimed at reducing mortality., Competing Interests: Declaration of competing interest None to declare., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

To assess the association between hyponatraemia and long-term functional outcome and other relevant outcomes in patients with aneurysmal subarachnoid haemorrhage (aSAH) we conducted a prospective cohort study in a Neurosciences Intensive Care Unit (ICU) in Sydney, Australia. The primary exposure variable was hyponatraemia (Na + <135 mmol/L). The primary outcome was favourable outcome, a score of 5-8 on the extended Glasgow Outcome Score (GOSe) at 12 months. We also measured mortality, the incidence of delayed cerebral ischaemia (DCI) and cerebral arterial vasospasm and duration of ICU and hospital admission. There were 200 participants, 111 (56%) developed hyponatraemia. Hyponatraemia was not associated with favourable outcome at 12 months (unadjusted odds ratio [OR] OR 1.31, 95% confidence interval [CI] 0.65-2.65, p = 0.56). The result was similar after adjustment for baseline covariates (adjusted OR 0.60, 95% CI 0.16-1.99, p = 0.43). There was no association between hyponatraemia and the incidence of DCI (OR 0.95, 95% CI 0.46 to 2.0, p > 0.99) nor cerebral arterial vasospasm (OR 1.4, 95% CI 0.8 to 2.5, p = 0.27). Those who developed hyponatraemia had a longer median duration of ICU admission (17 days, interquartile range [IQR] 12 to 20, compared to 13 days, IQR 8-21, p = 0.02) and longer median duration of hospital admission (24 days, IQR 21-30, compared to 22 days IQR 14-31, p = 0.05). While hyponatraemia is common following aSAH, it is not associated with worse long-term functional outcome, increased rate of DCI, nor cerebral arterial vasospasm. Hyponatraemia in patients with aSAH was associated with longer duration of ICU and hospital admission., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The first consensus standardised neonatal parenteral nutrition formulations were implemented in many neonatal units in Australia in 2012. The current update involving 49 units from Australia, New Zealand, Singapore, Malaysia and India was conducted between September 2015 and December 2017 with the aim to review and update the 2012 formulations and guidelines., Methods: A systematic review of available evidence for each parenteral nutrient was undertaken and new standardised formulations and guidelines were developed., Results: Five existing preterm Amino acid-Dextrose formulations have been modified and two new concentrated Amino acid-Dextrose formulations added to optimise amino acid and nutrient intake according to gestation. Organic phosphate has replaced inorganic phosphate allowing for an increase in calcium and phosphate content, and acetate reduced. Lipid emulsions are unchanged, with both SMOFlipid (Fresenius Kabi, Australia) and ClinOleic (Baxter Healthcare, Australia) preparations included. The physicochemical compatibility and stability of all formulations have been tested and confirmed. Guidelines to standardise the parenteral nutrition clinical practice across facilities have also been developed., Conclusions: The 2017 PN formulations and guidelines developed by the 2017 Neonatal Parenteral Nutrition Consensus Group offer concise and practical instructions to clinicians on how to implement current and up-to-date evidence based PN to the NICU population.

The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case-control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed before the age of 40 years, recorded on the state Cancer Registries. Controls were women without breast cancer, frequency-matched for age, randomly selected from electoral rolls. Full manual sequencing of the coding region of BRCA1 was conducted in a randomly stratified sample of 91 cases; 47 with, and 44 without, a family history of breast cancer in a first- or second-degree relative. All detected variants were tested in a random sample of 67 controls. Three cases with a (protein-truncating) mutation were detected. Only one case had a family history; her mother had breast cancer, but did not carry the mutation. The proportion of Australian women with breast cancer before age 40 who carry a germline mutation in BRCA1 was estimated to be 3.8% (95% CI 0.3-12.6%). Seven rare variants were also detected, but for none was there evidence of a strong effect on breast cancer susceptibility. Therefore, on a population basis, rare variants are likely to contribute little to breast cancer incidence.