Space launch costs have fallen dramatically over the past six decades, opening new economic and scientific frontiers. Yet precise, long-term estimates of these cost reductions remain sparse, and the underlying rate of technological learning is poorly understood. We introduce the largest standardized dataset of rocket launches to date, covering more than 4,400 launches (1960 to 2025) across 16 spacefaring geographical entities and show that the average cost of sending a kilogram to orbit has dropped from 87,023 USD in 1960 to 3,868 USD in 2025. Using a Wright's Law framework, we estimate that for each doubling of cumulative payload to orbit, the average cost of sending a kilogram to orbit decreases by 21.2%, revealing an exceptionally steep experience curve, outpacing that of other transformative technologies, including 19th-century steamship freight and modern solar photovoltaics. We leverage our empirical model to produce out-of-sample projections under a set of scenario-based and data-driven approaches. In our central estimate, the average cost is expected to fall to 1,600 USD/kg by 2030 and 300 USD/kg by 2040. Nonetheless, geopolitical shifts, potential monopolistic behavior in commercial launch markets, and the rising challenges of orbital debris may temper these gains. Overall, our findings underscore the importance of continued research and policy focus on launch technology, given that breakthroughs in cost reduction could accelerate the evolution of the space economy and its diverse near-term applications.
Defoliating (D) strains of the vascular wilt fungus Verticillium dahliae cause severe yield losses in cotton and olive, but the genetic basis of this pathotype remained unknown. Using comparative genomics, functional genetics, structural analysis, and phylogenomics, we identify a D-pathotype-specific genomic region encoding two duplicated secreted effector genes. Simultaneous deletion of both copies abolishes pathogenicity and defoliation in cotton and olive, and affects virulence in Nicotiana benthamiana and Arabidopsis thaliana. Expression of the effector in non-defoliating strains induces cotton defoliation, and purified protein causes wilting and leaf drop. Structural analyses reveal a previously uncharacterized protein fold conserved across Verticillium and Fusarium species, with evidence of functional diversification and host specificity. Phylogenomic and genomic context analyses indicate repeated horizontal transfer mediated by giant transposable elements known as Starships. Together, these findings identify the D effector as a central determinant of defoliation and virulence and show how Starship-mediated gene transfer drives emergence of an agriculturally important fungal trait.
Rapid adaptation in fungal plant pathogens is often attributed to sexual recombination, yet many important pathogens are largely clonal. We investigated how genetic and phenotypic diversity arises in the predominantly asexual fungus Colletotrichum nymphaeae, the main cause of strawberry anthracnose in Europe and North America. We performed comparative genomics on 36 C. nymphaeae genomes and 45 other Colletotrichum genomes sampled from strawberry or from closely related species, assessing population structure, transposable element (TE) content, genome compartmentalisation and signatures of horizontal transfer, and linked these features to phenotypic variation and virulence. Colletotrichum nymphaeae consists of three major lineages, with a globally distributed clonal lineage showing high variability in morphology and virulence. Extensive variation in TE content was detected among and within lineages. Genomes are compartmentalised into core regions and TE-rich accessory regions (ARs) that cluster by lineage and are enriched for gene duplications, genes under relaxed selection and genes linked to stress, virulence and fungicide resistance. We identified a Starship element and a 2 kb region containing two effector genes that were horizontally acquired. TE-rich ARs and horizontal gene transfer drive diversification in this largely asexual pathogen, shaping its evolution and posing challenges for durable strawberry anthracnose management.
Previously considered rare, penicillin-susceptible Staphylococcus aureus (PSSA) bacteraemia has re-emerged worldwide. Although benzylpenicillin might offer advantages in terms of pharmacokinetic and adverse effect profiles, anti-staphylococcal penicillins are recommended for serious infections because of concern over undetected penicillin resistance. We aimed to compare benzylpenicillin with anti-staphylococcal penicillins (cloxacillin or flucloxacillin) for the treatment of PSSA bacteraemia in adults. This investigator-initiated, international, multicentre, open-label, non-inferiority, randomised controlled trial was conducted within the PSSA silo of the backbone domain of the ongoing S aureus Network Adaptive Platform (SNAP) trial. We enrolled patients of all ages who were admitted with S aureus bacteraemia at 67 hospitals across Australia, New Zealand, Canada, Israel, the Netherlands, the UK, Singapore, and South Africa. Herein, we report results for adult patients (aged ≥18 years). Participants were randomly allocated 1:1 to receive either benzylpenicillin, or flucloxacillin or cloxacillin. Trial staff, staff caring for participants, and participants were aware of the treatment allocated and received. Cloxacillin was used only where flucloxacillin was not available (ie, Canada, Israel, Singapore, and South Africa). Recommended standard dosing for benzylpenicillin was 1·8 g intravenously once every 4 h or 2·4 g once every 6 h; for flucloxacillin 2·0 g intravenously once every 6 h; and for cloxacillin 2·0 g intravenously once every 4 h. The primary outcome was all-cause mortality 90 days after platform entry, assessed in the intention-to-treat population, including all patients with available data. The primary outcome was analysed by use of a hierarchical Bayesian logistic regression model, with non-inferiority of benzylpenicillin defined as an adjusted odds ratio (OR) of less than 1·20. Analyses occurred after every 500 participants reached 90-day follow-up. The SNAP trial is registered with ClinicalTrials.gov (NCT05137119) and is ongoing. Following the fourth interim analysis, the data and safety monitoring committee recommended ceasing recruitment before prespecified stopping thresholds were reached because of increased acute kidney injury (AKI) in participants receiving flucloxacillin or cloxacillin, and the PSSA silo was closed for recruitment on Aug 7, 2024. Between Feb 18, 2022, and June 21, 2024, of 493 adults with PSSA bacteraemia, 125 were randomly assigned to the flucloxacillin or cloxacillin group and 156 to the benzylpenicillin group. The median age was 67 years (IQR 56-77), 87 (31%) were female, and 194 (69%) were male. 21 (14%) of 152 in the benzylpenicillin group and 26 (22%) of 121 in the flucloxacillin or cloxacillin group met the primary outcome of death at 90 days (adjusted OR 0·67, 95% credible interval [CrI] 0·35-1·28), with a posterior probability of benzylpenicillin non-inferiority of 96·1% and of benzylpenicillin superiority of 88·9%. AKI occurred in 17 (11%) of 153 patients in the benzylpenicillin group and 27 (22%) of 124 patients in the flucloxacillin or cloxacillin group (adjusted OR 0·50, 95% CrI 0·26-0·94), corresponding to a posterior probability of non-inferiority of benzylpenicillin of 99·8% and superiority of benzylpenicillin of 98·4%. Seven total serious adverse reactions were reported from six (4%) of 156 participants in the benzylpenicillin group and ten were reported from nine (7%) of 125 participants in the flucloxacillin or cloxacillin group. Although the prespecified non-inferiority criterion for benzylpenicillin was not met, the probability of benzylpenicillin being non-inferior for mortality, along with a reduction in risk of AKI, indicates that benzylpenicillin should be preferred over flucloxacillin or cloxacillin for treatment of PSSA bacteraemia in adults. National Health and Medical Research Council, Medical Research Future Fund, Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, UMC Utrecht, ZonMW Good Use of Medicines programme, Health Research Council of New Zealand, Starship Foundation, National Healthcare Group Fund, National Medical Research Council, National Institute for Health and Care Research, Medical Research Council, and Paterson Family Foundation.
Intracranial pressure (ICP) is the management focus for improving outcomes after moderate to severe pediatric traumatic brain injury (pTBI). However, contemporary treatment thresholds have limited pediatric specific evidence. To explore ICP thresholds associated with improved functional outcomes in pTBI. This study is a secondary analysis from Studying Trends of AutoRegulation in Severe Head Injury in Pediatrics (STARSHIP) research database, a prospective, multicenter, observational study that enrolled children 16 years and younger requiring invasive arterial and intracranial pressure (ICP) monitoring for clinical management of pTBI between July 1, 2018, to March 30, 2023, from 10 pediatric intensive care units (PICUs) in the UK and completed data in June 2024. Continuous invasive ICP data during a PICU stay. The primary outcome was 12-month Glasgow Outcome Scale Extended for Pediatrics score. ICP dynamics were explored using minute-level ICP calculated from 10-second averages and thresholds tested across 5 to 20 mm Hg. Confounding was addressed using prognostic sliding dichotomy (baseline injury severity) and Pediatric Intensity Level of Therapy score-stratified analyses (treatment intensity). Sensitivity analyses were performed for robustness using propensity score matching, multivariable mixed-effects logistic regression, and marginal structural models. Among the 135 patients included, the median (IQR) age was 96 (26-152) months, and 105 (78%) patients were male. A median (IQR) of 153 (88-275) hours of ICP data were available per patient for 135 patients. Mean (SD) ICP was higher in patients with poor outcome (nonsurvivors vs survivors: 44 [23] mm Hg vs 17 [6] mm Hg; unfavorable vs favorable: 24 [16] mm Hg vs 17 [6] mm Hg). Thresholds of 14 to 15 mm Hg of ICP were identified as most discriminatory for outcome, with an increase in the odds of poor functional outcome at elevations above these levels, using both the static (odds ratio [OR], 6.1; 95% CI, 2.4-15.5; P < .001) and dynamic (dose: OR, 3.7; 95% CI, 1.5-9.3; P = .004; duration: OR, 3.5; 95% CI, 1.5-8.3; P = .007) analyses. Though treatment intensity was not independently associated with outcome or complications, effective ICP control across treatment levels was associated with more favorable prognosis. Sustained ICP greater than 15 mm Hg remained a prognostic factor for poor functional outcome at 12 months, a finding complemented by propensity score matching and causal modeling. In this study, sustained ICP elevations above 14 to 15 mm Hg were associated with poor long-term functional outcomes in pTBI warranting prospective evaluation. These findings suggest that the current treatment threshold of 20 mm Hg maybe too high for pTBI.
To quantify systemic exposure to budesonide following intratracheal administration; evaluate the impact of intratracheal budesonide on blood glucocorticoid activity (cortisol plus betamethasone as cortisol equivalents); and relate the latter to outcomes. Sub-study of the PLUSS randomized trial(ACTRN12617000322336) of intratracheal budesonide with surfactant versus surfactant alone. Among 63 infants enrolled at Kidz First Neonatal Care, Auckland, systemic exposure to intratracheal budesonide was low, and cortisol equivalents were similar between intervention groups at 36-48 h (adjusted-ratio-geometric-means = 1.16, 95% CI 0.52-2.57). Antenatal betamethasone <24 h before birth contributed to neonatal blood glucocorticoid activity for up to 24-48 h. Infants above the upper tertile for cortisol equivalents at <60 h, compared with those below the lower tertile, had increased likelihood of severe intraventricular hemorrhage and possibly death. Systemic exposure to intratracheal budesonide has little to no effect on cortisol equivalents at 36-48 h. High glucocorticoid activity after birth may be associated with poorer neonatal outcomes.
Digital tools are increasingly used to support recruitment and retention of participants in paediatric research, particularly since the COVID-19 pandemic. However, the extent of the evidence supporting this method in paediatric populations has yet to be evaluated. This scoping review aimed to review the literature on digital tools for recruitment and/or retention of participants in paediatric research, including emerging evidence following the pandemic. A scoping review was conducted following Joanna Briggs Institute methodology. We included peer-reviewed quantitative, qualitative, and mixed-method studies evaluating a digital tool for recruitment or retention in paediatric research in any patient population aged <13 years. Records were identified from systematic database searches with a librarian (EMBASE, MEDLINE, CINAHL), limited to English, from 2013 onwards (last search 03/07/2024), and manual searches. Records were screened and extracted independently in duplicate. The data were charted and narratively summarised. Sixty-one out of 4988 records were included. Most evaluations used an observational design; only 5 (8%) involved a randomised experiment. The host studies were mostly aiming to recruit children aged 5-12 years (n = 42; 69%), with a predominantly health promotion (n = 18; 30%), developmental (n = 12; 20%), or oncology (n = 9; 15%) focus. Most studies used multi-component digital interventions for recruitment (n = 39/53; 74%) or retention (n = 17/31; 55%). Social media (n = 33/52; 62%) and websites (n = 19/53; 36%) were most commonly used for recruitment, whereas text/instant messaging (n = 17/31; 55%) and email (n = 11/31; 36%) were the most common retention strategies. The estimates of recruitment and retention rates, and reach per digital tool varied widely between studies. Strategies in underserved populations reflected those used most commonly overall. Multi-component digital strategies were found to support a high rate of retention (84.1-90.7%) during pandemic restrictions. This scoping review highlights the broad array of digital tools that have been used to support recruitment and retention in studies of infants and children, including in subgroups of underserved populations and in response to the COVID-19 pandemic. Most evaluations were observational and examined multi-component digital interventions. The lack of studies with a robust analytical design in the literature signals a need for further high-quality, randomised, within-study evaluations following standardised reporting criteria. The protocol was registered on the Open Science Framework (OSF) at https://osf.io/ybfhr/ . Registered on July 5 2024.
Ewing sarcoma (EWS), rhabdomyosarcoma (RMS), and osteosarcoma (OSS) are rare in adults; efficacy and feasibility of treating adults with standard paediatric protocols (PP) are uncertain as chemotherapy protocols have been extrapolated from a paediatric population. A systematic review was conducted for EWS, RMS, and OSS using the Population, Intervention, Comparison, and Outcome (PICO) framework. PICO 1 compared adults treated with PP vs personalised "adult protocols" (non-PP). PICO 2 compared adults vs children treated with PP. PP was defined as: VDC/IE, VIDE for EWS; IVA, VAC for RMS; and MAP for OSS. 14, 13 and 9 studies for EWS, RMS and OSS were identified; majority were retrospective. Compared with non-PP, PP was associated with improved survival in adults with RMS (5-year OS of 56.7% vs 39.5% in a non-metastatic cohort, multivariate analysis, p = 0.042). There was limited robust data directly comparing PP vs non-PP in adults with EWS and OSS. Acknowledging many potential confounders, adequate chemotherapy exposure may be associated with improved survival across EWS, RMS and OSS. Compared to children, adults had lower chemotherapy exposure and differential toxicities: more peripheral neuropathy, but similar or reduced haematological toxicity. The treatment of adults with EWS, RMS, and OSS remains an area of unmet need. Adequate chemotherapy exposure and inclusion of disease-specific therapeutic agents may be important elements in the optimal treatment of adults. Referral to a specialised sarcoma reference centre is strongly recommended.
Whether treatment with balanced crystalloid fluid leads to better outcomes than 0.9% saline in children treated for septic shock is debated. In this pragmatic clinical trial conducted at 47 emergency departments in five countries, patients (2 months to <18 years of age) with suspected septic shock and abnormal perfusion were randomly assigned to receive fluid resuscitation with either balanced fluid or 0.9% saline for up to 48 hours. The primary outcome was a major adverse kidney event (a composite of death, new renal-replacement therapy, or persistent kidney dysfunction) at 30 days after enrollment or hospital discharge, whichever occurred first. Of 9041 enrolled patients, 277 (6.1%) in the balanced-fluid group and 282 (6.2%) in the 0.9%-saline group withdrew from the trial, leaving 4235 and 4247 patients, respectively, for analysis. A primary-outcome event occurred in 137 patients (3.4%) in the balanced-fluid group and in 124 (3.0%) in the 0.9%-saline group (difference, 0.4 percentage points; 95% confidence interval [CI], -0.5 to 1.3; risk ratio, 1.10; 95% CI, 0.88 to 1.40; P = 0.85). The median number of hospital-free days during 28 days after enrollment was 23 (interquartile range, 19 to 25) in both groups. Hyperchloremia occurred in 868 patients (31.4%) in the balanced-fluid group and in 1383 (49.0%) in the 0.9%-saline group; hypernatremia in 52 (1.8%) and 89 (3.1%), respectively; and hyperlactatemia in 260 (19.8%) and 228 (16.7%). No differences in other safety outcomes or adverse events were seen. Among children treated for septic shock, no significant difference was seen in the incidence of death, new renal-replacement therapy, or persistent kidney dysfunction when fluid resuscitation was administered with balanced fluid as compared with 0.9% saline. (Funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; PRoMPT BOLUS ClinicalTrials.gov number, NCT04102371.).
Tamariki (children) in Aotearoa New Zealand suffer high rates of respiratory morbidity. There are also geographic, socio-economic and ethnicity inequities, with tamariki Māori and Pacific children, experiencing the highest rates. Our aim was to survey New Zealand respiratory health services and identify gaps in delivery. We invited health practitioners from all districts to respond to an online survey and separately contacted individuals known to deliver paediatric respiratory care. We included medical, nursing and allied health staff and collated responses. There were 23 responses from 17 hospitals. Respiratory- and sleep-specialist senior medical officers (SMOs) were employed in only three major centres. Full time equivalent (FTE) for paediatricians with an interest (PWI) in respiratory care was evenly distributed with low numbers reported in the Northern region, Wellington and Canterbury. Senior nurse FTE was fairly constant across the country, except in the Northern region. Allied health staffing was inconsistent across the country with many districts in the Te Manawa Taki region reporting little or no respiratory physiotherapy staffing. More than half of districts reported limited or no access to videofluoroscopic swallow studies. There is poor access to chest computed tomography (CT) scanning under general anaesthetic in more than half of centres. Despite high levels of respiratory disease and morbidity, with serious disparities, there is inadequate staffing and provision of services. There is an urgent need for better co-ordination of care but a lack of both national and regional frameworks despite respiratory health being a current health target.
To describe the clinical characteristics of patients with Wolfram syndrome (WFS) and diabetes mellitus (DM) in Aotearoa, New Zealand. Review of response to therapy in those treated with glucagon-like peptide-1 receptor agonists (GLP1RA). This retrospective cohort study describes 7 patients with WFS1 genetic variants (1 patient with WFS-like syndrome), and DM from 5 New Zealand families (age range 5-33 years, 4 females, 3 males). All are receiving insulin. In 5 patients receiving GLP1RA therapy, we described their pre- and post-treatment biometric parameters, glycaemic control and visual acuity. Genetic testing identified compound heterozygous variants in the WFS1 gene (inherited from each parent) in five patients. Another two were heterozygous carriers of a single WFS1 missense variant, one of which was associated with uniparental disomy. Among patients receiving GLP1RA therapy, reductions were seen in HbA1c (mean 11.6 mmol/mol) and total daily insulin dose (mean 0.25 units/kg/day). We report genotypic and phenotypic variability in association with clinical features, including age of onset and severity. GLP1RA therapy was associated with improvements in diabetic control. Longer-term follow-up is required to monitor for sustained benefit and for progression or improvement in other WFS clinical features.
Despite strong evidence linking nutritional status to treatment efficacy and survival in pediatric cancer, significant knowledge gaps and practice variation persist globally. On 24th October 2025, the International Society of Paediatric Oncology (SIOP) Nutrition Network, in collaboration with Prinsess Máxima Center for Paediatric Oncology and the International Initiative for Pediatrics and Nutrition (IIPAN), convened the first global SIOP Nutrition Network Research Forum. The forum brought together 54 international experts from high-income countries and low- and middle-income countries to define global nutrition research strategies for pediatric oncology. The forum addressed six emerging domains: body composition and treatment outcomes; microbiome, micronutrient status and metabolic health; prehabilitation and rehabilitation strategies; validation of nutritional assessment tools, guideline development for high-income settings; insights from international multicentric research initiatives-the International Atomic Energy Agency (IAEA), SIOP Nutrition Network, the Adapted Resource and Implementation Application (ARIA) guide nutrition portal, the International Collaboration on Nutrition in Cancer (ICONIC) WHO knowledge portal; and IIPAN and the World Cancer Research Fund (WCRF) for funding strategies. Delegates identified three priority working groups, namely prehabilitation optimization, pharmacokinetics, and advocacy, with each outlining collaborative nutrition research priorities for the next five years. This forum represents a critical point in pediatric oncology nutrition research as it established the first coordinated and internationally endorsed roadmap to bridge gaps in cancer care and ensure standard nutrition care worldwide. The research priorities and collaborations will help in creating evidence to improve cancer treatment and survival rate for children globally.
Newborn screening for spinal muscular atrophy provides expedient access to diagnosis and treatment to transform health outcomes. However, because of a lack of high-quality practice standards and inequitable care and support access, health outcomes for affected children vary substantially. The study's purpose was to develop evidence and consensus-based recommendations to optimize and standardize clinical pathways. A total of 35 experts prepared systematic reviews and formulated recommendations using a modified Delphi process. Recommendations were developed for screening, diagnostic, and clinical domains, alongside guidelines to inform the content and quality of information provision and genetic counseling for families. The study generated 25 best practice recommendations. These encompassed pathways to expedite time to diagnosis and treatment through collaboration and coordination between health care services, standardization of screening and diagnostic methodologies, and equitable provision and timely access to specialist care and support. The study informs best practice within a new diagnostic and therapeutic era for spinal muscular atrophy by providing an evidence-based translational framework to improve the health and well-being of affected children. As implementation of these public health programs accelerate globally, this study provides health care professionals and policy makers with a template to develop feasible and equitable newborn screening programs for spinal muscular atrophy.
To synthesize evidence on the clinical utility of chest X-ray (CXR), laboratory and viral testing in infants with bronchiolitis, including in subgroups with unexpected deterioration or intensive care unit (ICU) admission (severe disease). An overview of reviews and systematic review of primary studies were conducted. MEDLINE, EMBASE, PubMed, Cochrane Library, CINAHL were searched (2000 to 19/02/25) for systematic reviews and primary studies evaluating investigations in bronchiolitis management at hospital. Risk of bias (ROBIS, NOS) and certainty of evidence (GRADE) were evaluated. Results were narratively synthesized. Thirty/28,602 publications were included (N = 23,605 infants, N = 59 studies; three systematic reviews [32 studies], 27 observational studies). In typical bronchiolitis: (1) CXR demonstrated insufficient diagnostic accuracy, increased antibiotic prescriptions, and was not associated with ICU length of stay (LOS) (very low quality of evidence); (2) Laboratory test results were not associated with mortality, and were inconsistent for LOS (very low quality of evidence); (3) Viral testing results were not associated with ICU admission, and were inconsistent for hospitalization (very low quality of evidence). In infants with severe disease: serum procalcitonin and c-reactive protein testing at ICU admission had some benefit in predicting bacterial co-infection and/or pneumonia (very low quality evidence). Evidence was lacking for infants with unexpected deterioration. Very low certainty evidence indicates that CXR, laboratory and viral testing may have limited clinical utility in individual management of typical bronchiolitis, and should not be routinely used in this group. Further research is required in subgroups with unexpected deterioration or severe disease.
Although the Fontan operation was originally performed as a single-stage procedure, staged palliation is currently the preferred approach. The current study aimed to evaluate the outcomes of the single-stage Fontan operation. A binational Fontan Registry (n = 1862) was analyzed to identify patients who underwent a single-stage Fontan operation. These patients were compared with staged Fontan patients in the Registry. Patients with atriopulmonary Fontan connections were excluded. The primary composite endpoint was postdischarge Fontan failure, encompassing death, heart transplantation, Fontan takedown or conversion, protein-losing enteropathy, plastic bronchitis, or New York Heart Association functional class III or IV. Other endpoints were early complications, including chylothorax, in-hospital death, time to first arrhythmia episode, time to first thromboembolic event, and first cardiac reintervention. Patients who underwent a single-stage Fontan operation (n = 176) were compared with those who underwent a staged Fontan operation (n = 1421). The median follow-up for the entire cohort was 11.0 years (interquartile range, 5.3-17.9 years). The majority of single-stage Fontan operations were lateral tunnel (86%; n = 152), which were performed before 2006 (169 of 176; 96%). There was no difference in freedom from Fontan failure between the 2 groups (P = .23; hazard ratio, 0.90; 95% confidence interval, 0.60-1.35). Propensity score matching yielded 262 patients (131 pairs) with similar freedom from Fontan failure (P = .72). There was no difference between the 2 groups in early complications or secondary endpoints. In a large binational Fontan population, 11% of patients underwent a single-stage Fontan operation over 48 years. There was no difference in the incidence of freedom from Fontan failure, chylothorax, or reinterventions between patients who underwent a staged Fontan operation and those who underwent a single-stage Fontan operation.
Acute kidney injury (AKI) is increasingly recognized as a critical and underdiagnosed condition among neonates, with significant short and long-term implications for survival, kidney function, and long-term cardiovascular health. Neonatal physiology, including ongoing nephrogenesis, immature renal haemodynamics, and limited glomerular filtration, makes this population vulnerable to AKI. Advances in consensus definitions, particularly the modified neonatal Kidney Disease Improving Global Outcomes (KDIGO) criteria, have enhanced epidemiologic understanding and facilitated global research collaboration. Despite this, significant variability in AKI surveillance, diagnosis, and follow-up persists. Recent research efforts within Australia emphasize the need to incorporate AKI metrics into quality registries and improve equity of kidney care for infants. Integration of protocolized monitoring, preventative strategies such as nephrotoxin stewardship and methylxanthine therapy, and long-term follow-up for AKI survivors are essential to mitigating progression to chronic kidney disease. This narrative review synthesizes evolving evidence in neonatal renal physiology, AKI definition and biomarkers, epidemiology, management, and policy directions, emphasizing opportunities for education, protocol development, and collaborative improvement across Australia, New Zealand and beyond.
Micronutrient abnormalities are common in children and young people (CYP) with cancer, yet their clinical implications remain unclear. This systematic review and meta-analysis examined the prevalence of micronutrient abnormalities and their associations with treatment complications and prognostic indicator outcomes in CYP undergoing cancer therapy. We searched PubMed, EMBASE and Cochrane Library (inception-April 2025) for studies evaluating blood micronutrient status in CYP (0-21 years) with cancer. Primary outcomes were treatment-related toxicities; secondary outcomes were prognostic indicators outcomes including overall survival (OS) and event free survival (EFS). Two reviewers screened, extracted data and assessed risk of bias (JBI). Where ≥2 studies reported similar outcomes, random-effects meta-analyses pooled RRs, ORs or HRs with 95% CIs. Ten studies involving 1,229 CYP were included. Micronutrient abnormalities were frequent: folate deficiency ranged from 10 to 56%, selenium 20-58%, and zinc 30-70%, with several micronutrients declining during treatment. Lower folate showed the strongest association with toxicity, with significantly increased risks of febrile neutropenia (RR 2.22), neutropenia (RR 2.30), and thrombocytopenia (RR 2.80). Lower selenium was linked to poorer survival in individual studies and consistently associated with more treatment complications, although pooled EFS estimates were non statistically significant. Zinc, vitamin B12, and copper showed no significant pooled associations with EFS, and evidence for vitamins A, C, E, and magnesium was limited or inconsistent. Micronutrient abnormalities, particularly low folate, selenium, and zinc, are prevalent in CYP undergoing cancer treatment, with folate showing the most consistent associations with treatment complications. This supports the need for routine monitoring; however, large international multicentre population-based and international mechanistic studies are warranted. PROSPERO Registration: Registration ID: CRD42025646467. Link: https://www.crd.york.ac.uk/PROSPERO/recorddashboard.
To describe anogenital examination findings in a large cohort seen for child sexual abuse concerns, with findings classified following current international guidelines. Retrospective review of records of the Starship Children's Hospital child protection team for all children and adolescents (0-17 years) seen over 20 years. A total of 4443 children and adolescents were seen, of whom 3942 (89%) were female. The age distribution was bimodal, with a small peak in childhood and a larger peak in adolescence. Anogenital examination occurred in 2975 (67%), more often in those < 8 years (1197/1394, 86%) compared to those 8 years and older (1778/3049, 58%), p < 0.0001. The proportion examined declined steadily, from 93% in 1999 to 54% in 2018. 2263 examinations (76%) were normal, 425 (14%) had findings unrelated to sexual abuse and 287 (10%) had abnormal findings possibly related to sexual abuse. Of 1426 examined at Tanner Stage 1, 41 (3%) had abnormal findings, compared to 246/1549 (16%) at Tanner Stages 2-5. Of 16 pregnant adolescents examined, 2 (13%) had anogenital findings of previous trauma. In adolescents examined acutely where semen was observed on Gram stain, 8/17 (47%) had anogenital findings of acute trauma. The cohort seen for sexual abuse concerns has changed over 20 years, becoming increasingly adolescent. This has resulted in a decrease in the proportion examined and an increase in the rate of abnormal findings. Anogenital examinations are often normal in pregnancy or with semen present, reinforcing the international consensus that normal does not mean nothing happened.
INTRODUCTION: The efficacy of endoscopic management of recurrent ureteropelvic junction obstruction (rUPJO) compared to redo pyeloplasty (RP) after primary intervention remains unclear. We performed a systematic review and meta-analysis (SR/MA) of comparative studies on endoscopic procedures (EP), specifically endopyelotomy or balloon dilation versus RP. METHODS: We conducted a PRISMA-compliant SR/MA registered in PROSPERO (CRD420251046758). We searched MEDLINE, Embase, Scopus, CINAHL, CENTRAL, and Web of Science without language or date restrictions (initial search in May 2025; updated in November 2025). Comparative studies evaluating EP versus RP for rUPJO were identified. Two reviewers performed screening, data extraction, and risk-of-bias assessment in duplicate. The outcomes assessed were treatment success (radiographic and/or functional patency, and/or symptom resolution) and perioperative complications. Subgroup analysis was conducted for adult vs pediatric patients. The Haenszel-Mantel Method with random-effects model meta-analyses generated pooled odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 1945 records were retrieved; ultimately, 12 studies with 549 patients (EP, n = 304; RP, n = 245) met the inclusion criteria. Definitions of success and follow-up duration varied across studies. Surgical approaches included open, laparoscopic, and robotic RP. EP techniques comprised endopyelotomy and balloon dilation, with selective use based on stricture length and vascular anatomy. Across all included comparative studies, RP demonstrated higher success than EP; the pooled effect size favored RP, with an OR of 6.32 (95% CI 3.25–12.32). Composite complication rates did not show a statistically significant difference between RP and EP 1.31 (95% CI 0.54–3.18). Secondary outcomes were heterogeneous but generally favored EP, including shorter operative time, shorter length of stay, and minimal blood loss. The heterogeneity among subgroups was low to moderate. The risk of bias assessment was determined to be high to serious, specifically due to confounders and retrospective designs, which introduced clinical selection bias and limited the overall quality of the evidence. CONCLUSIONS: For rUPJO, RP was associated with higher odds of success than endoscopic management, without a demonstrable difference in complications. EP may be appropriate in carefully selected, favorable strictures; however, current comparative data support RP as the more reliable salvage option. Future work should prioritize standardized outcome definitions, prospective risk-adjusted comparisons, and transparent reporting of complication severity to refine patient selection and quantify trade-offs between approaches.
Current guidelines for the management of meticillin-susceptible Staphyloccocus aureus bloodstream infection/bacteraemia (SAB) recommend intravenous (flu)cloxacillin as the first-line treatment. This is based on decades of clinical practice. The high acute kidney injury rates seen with (flu)cloxacillin in the recently published SNAP trial, which is the largest randomized clinical trial ever in S. aureus bacteraemia (SAB), shows us the need to regularly test and question our usual clinical practice. Acute kidney injury is common in SAB when high doses of (flu)cloxacillin are used. The contribution of (flu)cloxacillin to developing or exacerbating acute kidney injury is likely to have been under recognized until now. Caution needs to be taken with (flu)cloxacillin. Cefazolin provides a safer and equally efficacious treatment for SAB. We discuss how this new evidence might be combined with our existing knowledge and the results of the CloCeBa trial to guide us how to appropriately manage our patients.