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Early fluid balance and mortality following extracorporeal cardiopulmonary resuscitation: a high volume, single center study
No full textBackground: For patients supported with venoarterial extracorporeal membrane oxygenation (VA-ECMO), a positive cumulative fluid balance at day three has been associated with increased mortality. However, there is limited evidence examining this association in patients requiring extracorporeal cardiopulmonary resuscitation (ECPR). The aims of this study were to (1) to describe contemporary fluid practice in patients requiring ECPR and (2) assess the relationship between early cumulative fluid balance and 28-day mortality. Methods: This was a retrospective, single centre, observational study using data collected from the EXCEL registry and the hospital electronic medical record. All patients undergoing ECPR from January 2017 until December 2022 were identified using a prospectively collected database. Patients aged < 18 years old or had extra-corporeal support ceased prior to arrival to the intensive care unit were excluded. Fluid data was collected for days 1,2,3 and 7; and cumulative balances reported for day 3 and day 7. Results: 104 patients were identified, of which 100 were included. The mean age was 48.9 (SD 14.1) years, 72 (72%) were male. 54 (54%) were out-of-hospital cardiac arrests. Median low flow time was 43 (IQR 39–76) minutes. 51 (51%) had died by day 28. After adjusting for location of cardiac arrest, return of spontaneous circulation and duration of ECMO, a 1 L increase in cumulative fluid balance to the end of day 3 was not independently associated with 28-day mortality (adjusted OR 1.09 [95% CI 0.97–1.22]), however by day 7 this was independently associated with an 11% increased risk of 28-day mortality (adjusted OR 1.11 [95% CI 1.001–1.23]). Conclusion: A one litre increase in CFB at the end of day 3 was not associated with 28-day mortality; but a one litre increase in CFB by the end of day 7 was associated with an 11% increase in the odds of day 28 mortality. The impact of restrictive fluid management strategies in those requiring ECPR should be assessed in prospective trials
Circulating immune cells exhibit distinct traits linked to metastatic burden in breast cancer
No full textBACKGROUND: Circulating immune cells play a crucial role in the anti-tumour immune response, yet the systemic immune system in metastatic breast cancers is not fully characterised. Investigating the cellular and molecular changes in peripheral blood mononuclear cells (PBMCs) from breast cancer patients could elucidate the role of circulating immune cells in metastasis and aid in identifying biomarkers for disease burden and progression. METHODS: In this study, we characterised the systemic immune landscape associated with varying levels of metastatic burden by analysing the single-cell transcriptomes of PBMCs from breast cancer patients and healthy controls. Our research focused on identifying changes in immune cell composition, transcriptional programs, and immune-cell communication networks linked to metastatic burden. Additionally, we compared these PBMC features onto a single-cell atlas of primary breast tumours to study corresponding traits in tumour-infiltrating immune cells. RESULTS: In metastatic breast cancer, PBMCs exhibit a significant downregulation of the adaptive immune system and a decreased number and activity of unconventional T cells, such as γδ T cells. Additionally, metastatic burden is associated with impaired cell communication pathways involved in immunomodulatory functions. We also identified a gene signature derived from myeloid cells shared between tumour immune infiltrates and circulating immune cells in breast cancer patients. CONCLUSIONS: Our study provides a comprehensive single-cell molecular profile of the peripheral immune system in breast cancer, offering a valuable resource for understanding metastatic disease in terms of tumour burden. By identifying immune traits linked to metastasis, we have unveiled potential new biomarkers of metastatic disease
A Positive-Reinforcement Training Regimen for Refined Sample Collection in Laboratory Pigs
No full textPositive-reinforcement training of laboratory pigs can reduce the reliance on forced manual restraint and anaesthesia for sample collection, reducing stress and physiological disruption. Training regimens for laboratory pigs typically rely on specialised equipment for restraint, such as Panepinto slings, with a time investment that may not be justified for short-term studies. These training regimens also commonly rely on pigs being lifted into sling restraints, which is not practical for studies involving large pigs. We developed and assessed a rapid, three-phase, positive-reinforcement training regimen for both individually housed and group-housed laboratory pigs to facilitate the collection of minimally invasive samples consciously and voluntarily. The time to complete each phase of training in both individually housed and group-housed pigs was recorded. The behaviour of the individually housed pigs was assessed via an ethogram of behaviours exhibited during a human approach test, and stress response was assessed by analysing salivary corticosterone. The rapid, positive-reinforcement training regimen successfully facilitated oral swabbing, rectal swabbing and rectal thermometer insertion from individually housed (within 18 days) and group-housed (within 6 days) pigs. The trained pigs displayed increasing positive behaviours, no or very few negative behaviours and corticosterone levels within normal limits throughout the study. This training regimen provides a practical and welfare-positive tool for the collection of minimally invasive samples from both small and large laboratory pigs, with a low time investment of 2-5 min/pig/day without the need for specialised restraint equipment
Routine Quality-of-Life Measurement in Residential Aged Care: Staff, Resident, and Family Perspectives
No full textBACKGROUND AND OBJECTIVES: There is interest in routinely measuring quality of life (QoL) in aged care homes, evidenced by the Australian Government's implementation of QoL as a mandatory quality indicator. This study explores views of aged care staff, residents, and family members on the benefits, challenges, and feasibility of implementing routine QoL measures. METHODS: Qualitative data were gathered to explore staff, resident, and family perspectives on QoL measurement in aged care homes, including purpose, benefits, implementation, and best practice. Two staff workshops were conducted at different aged care homes, and semi-structured interviews were held with 29 proxies (9 family members and 20 staff) and 24 residents. Workshops and interviews were transcribed verbatim, and thematically analysed via a qualitative interpretive approach using NVivo software. RESULTS: Analysis yielded four key themes: (1) benefits of routine QoL measurement; (2) challenges in implementation; (3) best practice for collecting surveys; (4) validity concerns. Identified benefits included potentially improved care, monitoring service performance, and informing family members. Staff participants recommended integrating measures into existing care planning and having oversight from a registered nurse. Participants identified potential implementation challenges, including administrative burden, time and resourcing constraints, conflicts of interest, and resistance from staff, providers, and residents. CONCLUSIONS: This study identifies potential benefits to implementing routine QoL measurement in residential aged care homes. To maximise these benefits, it is important to consider how measurement can be integrated in ways that contribute to existing care planning and practices
Comparative Transcriptomic profiling of Pediatric Cardiomyopathy Arising from Chemotherapy and Inherited Mutations
No full text© 2025 Fatemeh Fardi GolyanAnthracyclines remain foundational in paediatric oncology protocols because of their broad anti-neoplastic efficacy. Nevertheless, their therapeutic window is narrowed by a well-recognized, cumulative and dose-dependent cardiotoxicity: clinical event rates climb from ~7% at 150 mg m-2 to >60% at 550 mg m-2 of cumulative doxorubicin equivalents, and toxicity may manifest years after treatment, culminating in anthracycline-induced heart failure (AHF). Inherited dilated cardiomyopathy (DCM), driven largely by pathogenic variants in genes governing sarcomeric or nuclear architecture, constitutes the most common genetic cause of paediatric heart failure, accounting for roughly one-third to one-half of cases and contributing substantially to early transplant or mortality risk.
Although AHF and DCM arise from fundamentally different insults, chemotherapy-mediated injury versus germline structural disruption, they converge phenotypically, sharing progressive ventricular dilation, systolic dysfunction, and profound deficits in myocardial energetics. While reactivation of foetal gene programs has been previously reported in dilated cardiomyopathy, the extent to which anthracycline-induced heart failure engages similar transcriptional pathways remain unknown. To date, no systematic investigation has explored this phenomenon in human myocardium, making this study the first to address it in the context of chemotherapy-induced cardiomyopathy. To close these knowledge gaps, we applied single-nucleus RNA sequencing (snRNA-seq) to chart the transcriptomic landscape of the paediatric left ventricle across four biologically and clinically informative states: foetal (developmental reference), non-diseased donor (ND), genetically determined DCM, and AHF. Analysis of 103,212 high-quality nuclei from apical ventricular myocardium produced a comprehensive, cell-resolved atlas of paediatric heart biology. Differential expression analyses identified that cardiomyocytes and fibroblasts as the most transcriptionally populations in disease, each displaying discrete yet partially overlapping perturbations. A dominant shared signal was the coordinated downregulation of genes involved in mitochondrial oxidative phosphorylation and fatty-acid beta-oxidation, indicating a common disturbance in cellular energy metabolism across cardiomyopathy subtypes. By contrast, DCM showed selective enrichment of cytoskeletal-remodeling and sarcomeric-assembly transcripts, whereas AHF was characterized by heightened DNA-damage response elements and oxidative redox stress pathways findings consistent with anthracycline-mediated genotoxicity. Both diseases demonstrated partial re-activating of foetal transcriptional programs within cardiomyocytes and fibroblasts; however, the specific gene cohorts re-engaged showed limited intersection, underscoring distinct adaptive trajectories.
Generally, these data yield the first integrated single-nucleus transcriptomic atlas of paediatric heart failure encompassing both genetic and chemotherapeutic etiologies. The work delineates shared molecular liabilities, most notably mitochondrial dysfunction alongside disease-specific signatures that may inform precision diagnostics and targeted therapeutic development for paediatric cardiomyopathies
Retrospective Cohort Study of Low-Value Hysterectomy Before and After Publication of the National Heavy Bleeding Clinical Care Standard in Regional Victoria
No full textOBJECTIVE: To evaluate the prevalence of low-value care hysterectomy before and after publication of the National Heavy Menstrual Bleeding Clinical Care Standard (HMB Standard) in a regional Victorian hospital. The secondary aim was to assess whether compliance with the HMB Standard improved. METHODS: Retrospective cohort design. All patients booked for a planned benign hysterectomy were included. Manual chart review was undertaken for demographics, surgical planning, procedure, and outcomes to 28 days. DESIGN SETTING: A single regional Victorian hospital within an area identified to be high volume for benign hysterectomy. PARTICIPANTS: Patients who planned benign hysterectomy in the 10 months prior (Group 1-Control) and 10 months after (Group 2-Post-intervention) publication of the HMB Standard in October 2017. MAIN OUTCOME MEASURES: Low-value hysterectomy was defined as the proportion of benign hysterectomies performed via the abdominal route in the absence of cancer or a previous caesarean section. RESULTS: There were 64 patients in Group 1 and 60 in Group 2 included. Low-value hysterectomy proportion had a non-significant change from 9.4% in Group 1 to 11.7% in Group 2, 95% confidence interval = [-0.1303, 0.0857]. Compliance to the HMB Standard had mixed results. CONCLUSIONS: There was no clinically significant change in low-value hysterectomy in the 10 months following publication of the HMB Standard, compared to 10 months prior, in a regional Victorian hospital. Uptake of therapeutic alternatives to hysterectomy was low
Comparison of Three Physician Global Assessment Instruments in Systemic Sclerosis
No full textOBJECTIVE: Physician global assessments (PhyGAs) are variably applied in systemic sclerosis (SSc) clinical trials. The comparability of different PhyGA results is unknown. We sought to assess the comparability of results from three different PhyGA instruments simultaneously applied in the Australian Scleroderma Cohort Study (ASCS). METHODS: Using data from 1,965 ASCS participants, we assessed the correlation between results of three PhyGA assessments: (1) overall health, (2) activity, and (3) damage. We evaluated the concordance of change in each PhyGA between study visits. Ordered logistic regression analysis was used to evaluate the clinical associations of each PhyGA. RESULTS: The absolute scores of each PhyGA were strongly correlated at individual study visits. Concordant changes of the PhyGA scores occurred between 50% of study visits. Only patient-reported breathlessness was associated with all three PhyGA scores (overall health: odds ratio [OR] 1.67, P < 0.01; activity: OR 1.44, P < 0.01; damage: OR 1.32, P < 0.01). Changes in physician-assessed activity scores were also associated with patient-reported worsening skin disease (OR 1.25, P = 0.03) and fecal incontinence (OR 1.23, P = 0.01), whereas damage scores were associated with respiratory disease (pulmonary arterial hypertension: OR 1.25, P = 0.03; chronic obstructive pulmonary disease: OR 1.37, P = 0.04), as well as skin scores (OR 1.02, P < 0.01) and fecal incontinence (OR 1.21, P = 0.02). CONCLUSION: PhyGAs of overall health, activity, and damage are each associated with different SSc features, and changes in different PhyGA scores are discordant 50% of the time. Our findings suggest results of variably worded PhyGAs are not directly interchangeable and support the development of a standardized PhyGA
Biomechanical Performance of Total Wrist Arthrodesis Plates With and Without Arthrodesis of the Carpometacarpal Joint
No full textBackground: It is unknown whether total wrist arthrodesis (TWA) should be performed with or without arthrodesis of the carpometacarpal joint (CMCJ). The aim of this study is to compare CMCJ-spanning TWA plates using 3D printed wrist arthrodesis model with and without arthrodesis of the CMCJ. Methods: Total wrist arthrodesis plates mounted to 3D printed models were tested under a 4-N bending load at 4 Hz for 50 000 cycles, increased by 15% every 10 000 cycles until failure. Results: Plates with arthrodesis CMCJ were stiffer and failed at a significantly greater load and number of cycles than plates mounted to models without CMCJ arthrodesis. The Synthes stainless steel locking TWA plate performed better than the Trimed plate applied to the model without CMCJ arthrodesis and the Acumed plate applied to the model with CMCJ arthrodesis. Based on these findings, we recommend arthrodesis of the CMCJ in TWA. Conclusions: Incorporation of the CMCJ in TWA may protect against plate failure. If arthrodesis of the CMCJ is not performed, plate removal should be considered before breakage occurs. Level of Evidence: IV
Simultaneous coinfection with influenza virus and an arbovirus impedes influenza-specific but not Semliki Forest virus–specific responses
No full textOutbreaks of respiratory virus infections and arbovirus infections both pose a substantial threat to global public health. Clinically, both types of infection range from mild to severe and coinfections may occur more commonly than supposed. Our previous experimental coinfection study in mice demonstrated that prior infection with the arbovirus Semliki Forest virus (SFV) negatively impacted immune responses to influenza A virus (IAV). Here, we investigate whether simultaneous coinfection impacts the outcome of immune responses or disease. Simultaneous SFV and IAV infection did not lead to exacerbated or attenuated disease compared with the single virus infection control groups. SFV brain virus titers and brain pathology, including inflammation and immune responses, were comparable in the coinfection and single infection groups. By contrast, there was enhanced IAV replication, but no exacerbated lung pathology in coinfected mice. The magnitude of IAV-specific CD8+ T-cell responses in the lungs was lower compared with IAV-only infection. Considered along with our previous study, this study provides evidence that the timing of viral coinfection is pivotal in determining effects on immune responses, pathological changes and disease outcome
Life cycle environmental benchmarks for new-built Belgian residential buildings: A comparison of bottom-up and top-down approaches
No full text© 2025 Lise MoutonBuilding environmental impacts are increasingly quantified with life cycle assessment (LCA). In recent years, several countries have implemented LCA requirements in their building regulations. These regulations often include benchmark values, i.e. reference values with which designers can compare, or even binding limit values that must be achieved. Currently, most building regulations, including benchmark values, only focus on one environmental impact category, namely climate change. However, buildings contribute to multiple impact categories, some of which are currently critical at the global level.
Two approaches exist to develop environmental benchmark values for buildings: (1) bottom-up, based on a statistical analysis of reference buildings, and (2) top-down, where global environmental targets are translated into target values for buildings. The comparison of both reveals if the environmental impacts of typical buildings exceed global environmental targets that define the Earth’s carrying capacity. However, the current focus on climate change risks that other critical global carrying capacities are neglected.
This research compares bottom-up and top-down benchmark values of new-built Belgian residential buildings for multiple environmental impact categories, specifically all LCA impact indicators recommended by the European standards. The benchmark values obtained are applicable in the context of the TOTEM tool, i.e. the Belgian LCA tool for buildings.
The bottom-up benchmark values are derived from a statistical analysis of the TOTEM LCA results of 117 reference buildings, derived from 39 geometries and three materials applied to each. Three benchmark types are calculated, i.e. a limit (90th percentile), reference (median), and best-practice value (10th percentile), for all individual impact indicators and a single aggregated environmental impact.
The top-down benchmark values are derived by allocating global environmental target values to buildings in different steps: from global to Belgium, to the Belgian residential building sector, to new-built residential buildings in Belgium. In each step, multiple allocation principles are applied. Based on data availability and quality, ethical judgements, and recommendations from the literature, the preferred principles are: equal per capita allocation to Belgium, financial consumption expenditure allocation to the Belgian residential building sector, and an egalitarian allocation to m2 of new residential building floor area.
The three bottom-up benchmark values of 15 individual indicators are compared to the target values resulting from the different allocation principles, focusing on the recommended allocation approach. For five indicators, the bottom-up benchmark values exceed the recommended top-down target value, i.e. particulate matter emissions, eco-toxicity (freshwater), climate change, and abiotic resource depletion, both fossil fuels and minerals and metals. The main drivers for these impacts are operational energy use and conventional building materials. Key mitigation strategies thus include decarbonising the electricity mix, increasing renewable energy use, and adopting low-impact building materials. Impacts should also be reduced by minimising material use per m2 building floor area, extending building and material lifespans, and reusing materials to limit raw material demand. Reducing floor area per resident was identified as most effective but challenging to implement in practice. Therefore, a combination of innovative mitigation measures is needed to reduce building environmental impacts to achieve the targets