Victorian Heart Hospital

Importance: Coronary artery calcium (CAC) scoring provides prognostic information, especially in patients at intermediate risk for coronary artery disease (CAD). However, the benefit of combining CAC score with a primary prevention strategy has not been tested in a randomized trial. Objective: To assess whether combining the CAC score with a prevention strategy can be used to limit plaque progression in intermediate-risk patients with a family history of premature CAD. Design, Setting, and Participants: Prospective, randomized, open-blinded end point clinical trial in 7 hospitals across Australia (between 2013 and 2020; the last date of follow-up was June 5, 2021). Asymptomatic people aged 40 to 70 years with a first-degree relative with CAD onset at younger than 60 years old or second-degree relative with onset at younger than 50 years old were recruited from the community. Interventions: Intermediate-risk participants underwent CAC scoring. Those with a CAC score greater than 0 but less than 400 underwent coronary computed tomography angiography (CCTA) and were randomized to CAC score-informed prevention or usual care. Main Outcomes and Measures: Follow-up CCTA was obtained at 3 years, with plaque volume measured by an independent core laboratory. The primary outcome was total plaque volume, with further analysis for calcified and noncalcified plaque volume. Results: This study included 365 participants (mean [SD] age, 58 [6] years; 57.5% male); 179 in the CAC score-informed and 186 in the usual care groups. Compared with usual care, the CAC score-informed group showed a sustained reduction in total (mean [SD], -3 [31] mg/dL vs -56 [38] mg/dL; P < .001) and LDL (mean [SD], -2 [31] vs -51 [36] mg/dL; P < .001) cholesterol levels at 3 years, which was associated with a reduction in pooled cohort equation risk calculation (mean [SD], 2.1% [2.9%] vs 0.5% [2.9%]; P < .001). Plaque progression was greater in usual care than CAC score-informed participants for total plaque volume (mean [SD], 24.9 [37.7] mm3 vs 15.4 [30.9] mm3; P = .009), noncalcified plaque volume (mean [SD], 15.7 [32.2] mm3 vs 5.6 [28.5] mm3; P = .002), and fibrofatty and necrotic core plaque volume (mean [SD], 4.5 [25.8] mm3 vs -0.8 [12.6] mm3; P = .02). These plaque volume changes were independent of other risk factors including baseline plaque volume, blood pressure, and lipid profile. Conclusions and Relevance: The combination of CAC score with a primary prevention strategy in intermediate-risk patients with a family history of CAD was associated with reduction of atherogenic lipids and slower plaque progression compared with usual care. These data support the use of CAC score to assist intensive preventive strategies in intermediate-risk patients. Trial Registration: anzctr.org.au Identifier: ACTRN12614001294640.

Sugarcane (Saccharum sp.) plants are grown in warmer climates throughout the world and processed to produce sugar as well as other useful byproducts such as molasses and bagasse. Sugarcane is rich in (poly)phenols, but there has been no attempt to critically evaluate the published information based on the use of suitable methodologies. The objective of this review is to evaluate the quantitative and qualitative (poly)phenolic profiles of individual parts of the sugarcane plant and its multiple industrial products, which will help develop new processes and uses for sugarcane (poly)phenols. The quantitative analysis involves the examination of extraction, concentration, and analytical techniques used in each study for each plant part and product. The qualitative analysis indicates the identification of various (poly)phenols throughout the sugarcane processing chain, using only compounds elucidated through robust analytical methodologies such as mass spectrometry or nuclear magnetic resonance. In conclusion, sugarcane (poly)phenols are predominantly flavonoids and phenolic acids. The main flavonoids, derivatives of apigenin, luteolin, and tricin, with a substantial proportion of C-glycosides, are consistently found across all phases of sugarcane processing. The principal phenolic acids reported throughout the process include chlorogenic acids, as well as ferulic and caffeic acids mostly observed after hydrolysis. The derivation of precise quantitative information across publications is impeded by inconsistencies in analytical methodologies. The presence of multiple (poly)phenols with potential benefits for industrial applications and for health suggests sugarcane could be a useful provider of valuable compounds for future use in research and industrial processes.

Regulatory T cells (Tregs) are key immune regulators that have shown promise in enhancing cardiac repair post-MI, although the mechanisms remain elusive. Here, we show that rapidly increasing Treg number in the circulation post-MI via systemic administration of exogenous Tregs improves cardiac function in male mice, by limiting cardiomyocyte death and reducing fibrosis. Mechanistically, exogenous Tregs quickly home to the infarcted heart and adopt an injury-specific transcriptome that mediates repair by modulating monocytes/macrophages. Specially, Tregs lead to a reduction in pro-inflammatory Ly6CHi CCR2+ monocytes/macrophages accompanied by a rapid shift of macrophages towards a pro-repair phenotype. Additionally, exogenous Treg-derived factors, including nidogen-1 and IL-10, along with a decrease in cardiac CD8+ T cell number, mediate the reduction of the pro-inflammatory monocyte/macrophage subset in the heart. Supporting the pivotal role of IL-10, exogenous Tregs knocked out for IL-10 lose their pro-repair capabilities. Together, this study highlights the beneficial use of a Treg-based therapeutic approach for cardiac repair with important mechanistic insights that could facilitate the development of novel immunotherapies for MI. After myocardial infarction, excessive inflammation impairs heart repair, leading to reduced cardiac function. Here, the authors show that treatment with anti-inflammatory immune cells (regulatory T cells) improves cardiac repair by modulating the activity of a specific subset of macrophages in the heart.

(Poly)phenols inhibit α-amylase by directly binding to the enzyme and/or by forming starch-polyphenol complexes. Conventional methods using starch as the substrate measure inhibition from both mechanisms, whereas the use of shorter oligosaccharides as substrates exclusively measures the direct interaction of (poly)phenols with the enzyme. In this study, using a chromatography-based method and a short oligosaccharide as the substrate, we investigated the detailed structural prerequisites for the direct inhibition of human salivary and pancreatic α-amylases by over 50 (poly)phenols from the (poly)phenol groups: flavonols, flavones, flavanones, flavan-3-ols, polymethoxyflavones, isoflavones, anthocyanidins and phenolic acids. Despite being structurally very similar (97% sequence homology), human salivary and pancreatic α-amylases were inhibited to different extents by the tested (poly)phenols. The most potent human salivary α-amylase inhibitors were luteolin and pelargonidin, while the methoxylated anthocyanidins, peonidin and petunidin, significantly blocked pancreatic enzyme activity. B-ring methoxylation of anthocyanidins increased inhibition against both human α-amylases while hydroxyl groups at C3 and B3' acted antagonistically in human salivary inhibition. C4 carbonyl reduction, or the positive charge on the flavonoid structure, was the key structural feature for human pancreatic inhibition. B-ring glycosylation did not affect salivary enzyme inhibition, but increased pancreatic enzyme inhibition when compared to its corresponding aglycone. Overall, our findings indicate that the efficacy of interaction with human α-amylase is mainly influenced by the type and placement of functional groups rather than the number of hydroxyl groups and molecular weight.

BACKGROUND AND AIMS: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndrome (ACS). Recent data suggest a harmful association of dual antiplatelet therapy compared with single antiplatelet therapy following SCAD. This study investigated independent predictors of major adverse cardiovascular events (MACEs) and recurrence in patients with SCAD. METHODS: This multicentre cohort study involving 23 Australian and New Zealand sites included patients aged ≥18 years with an ACS due to SCAD confirmed on core laboratory adjudication. Multivariable Cox proportional hazard models analysed predictors for the primary MACE outcome. RESULTS: Among 586 patients, 505 (150 prospective, 355 retrospective) with SCAD confirmed by core laboratory adjudication, mean age was 52.2 ± 10.6 years, 88.6% were female, and 74.5% were Caucasian. At long-term follow-up (median 21 months), MACE and SCAD recurrence occurred in 8.6% and 3.6% of patients, respectively. Oral anticoagulation on discharge [adjusted hazard ratio (aHR) 3.8, 95% confidence interval (CI) 1.6-9.3, P = .003], ticagrelor combined with aspirin (aHR 1.8, 95% CI 1.04-3.2, P = .037), fibromuscular dysplasia (aHR 2.2, 95% CI 1.05-4.5, P = .037), and history of stroke (aHR 3.8, 95% CI 1.2-12.2, P = .03) were independently associated with higher MACE. Fibromuscular dysplasia (aHR 3.9, 95% CI 1.5-26.5, P = .01), ticagrelor combined with aspirin (aHR 2.6, 95% CI 2.1-5.3, P = .01), and history of stroke (aHR 6.2, 95% CI 1.8-9.5, P = .01) were also associated with higher SCAD recurrence. CONCLUSIONS: The findings support the hypothesis that SCAD is primarily caused by intramural bleeding, with a harmful association of more potent antiplatelet therapy and anticoagulation with adverse cardiovascular outcomes.

AIMS: Pulsed field ablation (PFA) for the treatment of atrial fibrillation (AF) potentially offers improved safety and procedural efficiencies compared with thermal ablation. Opportunities remain to improve effective circumferential lesion delivery, safety, and workflow of first-generation PFA systems. In this study, we aim to evaluate the initial clinical experience with a balloon-in-basket, 3D integrated PFA system with a purpose-built form factor for pulmonary vein (PV) isolation. METHODS AND RESULTS: The VOLT CE Mark Study is a pre-market, prospective, multi-centre, single-arm study to evaluate the safety and effectiveness of the Volt™ PFA system for the treatment of paroxysmal (PAF) or persistent AF (PersAF). Feasibility sub-study subjects underwent phrenic nerve evaluation, endoscopy, chest computed tomography, and cerebral magnetic resonance imaging. Study endpoints were the rate of primary serious adverse event within 7 days and acute procedural effectiveness. A total of 32 subjects (age 61.6 ± 9.6 years, 65.6% male, 84.4% PAF) were enrolled and treated in the feasibility sub-study and completed a 30-day follow-up. Acute effectiveness was achieved in 99.2% (127/128) of treated PVs (96.9% of subjects, 31/32) with 23.8 ± 4.2 PFA applications/subject. Procedure, fluoroscopy, LA dwell, and transpired ablation times were 124.6 ± 28.1, 19.8 ± 8.9, 53.0 ± 21.0, and 48.0 ± 19.9 min, respectively. Systematic assessments of initial safety revealed no phrenic nerve injury, pulmonary vein stenosis, or oesophageal lesions causally related to the PFA system and three subjects with silent cerebral lesions (9.4%). There were no primary serious adverse events. CONCLUSION: The initial clinical use of the Volt PFA System demonstrates acute safety and effectiveness in the treatment of symptomatic, drug refractory AF.

Importance: Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Protein loading appears nephroprotective; thus, continuous hyperoncotic albumin infusion may impact AKI following high-risk cardiac surgery. Objective: To evaluate the effect of postoperative 20% albumin infusion compared with usual care on the occurrence of AKI in high-risk cardiac surgery patients. Design, Setting, and Participants: This was an investigator-initiated randomized multicenter open-label pragmatic clinical trial. Participants were stratified by site and estimated glomerular filtration rate (eGFR) above and below 60 mL/min/1.73 m2. The study was conducted at 7 cardiac centers in Australia and Italy between July 2019 and August 2024. Patients undergoing on-pump cardiac surgery with a preoperative eGFR of greater than 15 mL/min/1.73 m2 and less than 60 mL/min/1.73 m2 or undergoing a combined cardiac surgical procedure or major aortic surgery were included, excluding those who were in intensive care for longer than 6 hours following the index surgery, had a serum albumin level less than 20 g/L, were dialysis dependent, had a previous kidney transplant, were receiving extracorporeal life support or ventricular assist device, or had an objection to receiving albumin or blood products. Interventions: Participants were randomized 1:1 within 6 hours after surgery to receive a 300-mL infusion of 20% albumin over 15 hours or usual care, as per clinician discretion. All patients received volume resuscitation and hemodynamic treatment according to participating centers' protocols. Main Outcomes and Measures: The primary outcome was stage 1-3 AKI according to the creatinine-based Kidney Disease Improving Global Outcomes definition. The main secondary outcomes included major adverse kidney events and mortality at hospital discharge or day 28 following randomization. Results: The primary analysis included 307 patients randomized to the 20% albumin group and 304 to usual care. The mean (SD) age was 69 (10.8) years, and 281 patients (45.8%) had an eGFR less than 60 mL/min/1.73 m2. The median (IQR) European System for Cardiac Operative Risk Evaluation score-II was 3.23 (1.91-5.30). AKI occurred in 150 of 307 patients in the albumin group (48.9%) vs 132 of 304 in usual care (43.4%) (unadjusted relative risk, 1.13; 95% CI, 0.95-1.34; P = .18; strata-adjusted relative risk, 1.12; 95% CI, 1.04-1.21; P = .003). This effect was more pronounced in patients with an eGFR of <60 mL/min/1.73 m2 (adjusted relative risk, 1.14; 95% CI; 1.07-1.22; P < .001). There were more blood transfusions given in the albumin group (116 [37.8%] vs 91 [29.9%]; P = .04) but no other significant differences in secondary outcomes. Conclusions and Relevance: In this study of cardiac surgery patients at high risk of AKI, an infusion of 20% albumin increased the risk of AKI. These findings do not support the routine use of hyperoncotic albumin infusion in patients undergoing high-risk cardiac surgery. Trial Registration: Anzctr.org.au Identifier: ACTRN12619001355167.

BACKGROUND: In the context of expanding digital health tools, the health system is ready for Learning Health System (LHS) models. These models, with proper governance and stakeholder engagement, enable the integration of digital infrastructure to provide feedback to all relevant parties including clinicians and consumers on performance against best practice standards, as well as fostering innovation and aligning healthcare with patient needs. The LHS literature primarily includes opinion or consensus-based frameworks and lacks validation or evidence of benefit. Our aim was to outline a rigorously codesigned, evidence-based LHS framework and present a national case study of an LHS-aligned national stroke program that has delivered clinical benefit. MAIN TEXT: Current core components of a LHS involve capturing evidence from communities and stakeholders (quadrant 1), integrating evidence from research findings (quadrant 2), leveraging evidence from data and practice (quadrant 3), and generating evidence from implementation (quadrant 4) for iterative system-level improvement. The Australian Stroke program was selected as the case study as it provides an exemplar of how an iterative LHS works in practice at a national level encompassing and integrating evidence from all four LHS quadrants. Using this case study, we demonstrate how to apply evidence-based processes to healthcare improvement and embed real-world research for optimising healthcare improvement. We emphasize the transition from research as an endpoint, to research as an enabler and a solution for impact in healthcare improvement. CONCLUSIONS: The Australian Stroke program has nationally improved stroke care since 2007, showcasing the value of integrated LHS-aligned approaches for tangible impact on outcomes. This LHS case study is a practical example for other health conditions and settings to follow suit.

One approach to controlling type 2 diabetes (T2D) is to lower postprandial glucose spikes by slowing down the digestion of carbohydrates and the absorption of glucose in the small intestine. The consumption of walnuts is associated with a reduced risk of chronic diseases and T2D, suggested to be partly due to the high content of (poly)phenols. This study evaluated, for the first time, the inhibitory effect of a (poly)phenol-rich walnut extract on human carbohydrate digesting enzymes (salivary and pancreatic α-amylases, brush border sucrase-isomaltase) and on glucose transport across fully differentiated human intestinal Caco-2/TC7 monolayers. The walnut extract was rich in multiple (poly)phenols (70 % w/w) as analysed by Folin-Ciocalteau and by LCMS. It exhibited potent inhibition of both human salivary (IC50: 32.2 ± 2.5 µg walnut (poly)phenols (WP)/mL) and pancreatic (IC50: 56.7 ± 1.7 µg WP/mL) α-amylases, with weaker effects on human sucrase (IC50: 990 ± 20 µg WP/mL), maltase (IC50: 1300 ± 80 µg WP/mL), and isomaltase (IC25: 830 ± 60 µg WP/mL) activities. Selected individual walnut (poly)phenols inhibited human salivary α-amylase in the order: 1,3,4,6-tetragalloylglucose > ellagic acid pentoside > 1,2,6-tri-O-galloyl-β-D-glucopyranose, with no inhibition by ellagic acid, gallic acid and 4-O-methylgallic acid. The (poly)phenol-rich walnut extract also attenuated (up to 59 %) the transfer of 2-deoxy-D-glucose across differentiated Caco-2/TC7 cell monolayers. This is the first report on the effect of (poly)phenol-rich extracts from any commonly-consumed nut kernel on any human starch-digesting enzyme, and suggests a mechanism through which walnut consumption may lower postprandial glucose spikes and contribute to their proposed health benefits.

Food innovation that utilises agricultural waste while enhancing nutritional value is important for waste valorisation and consumer health. This study investigated incorporating spinach (Spinacia oleracea), as a model leafy agricultural waste, into wheat bread. We analysed the nutrient content, colour, texture, sensory attributes and purchase/consume intention ratings. Adding 10–40% spinach (w/w) yielded loaves with similar heights but significantly different colour and texture (p &lt; 0.05) from white bread. Increasing spinach decreased total carbohydrates (including starch) while significantly increasing other nutrients (protein, fibre, iron, magnesium, potassium, zinc, calcium, vitamins A, C, E, folate, niacin, pyridoxine, nitrate/nitrite and polyphenols) (p &lt; 0.05). Spinach addition increased bread porosity, linked to higher pasting parameters (peak, trough, breakdown, final and setback viscosity) with reduced pasting time and temperature. Texture analysis resulted in decreased hardness, chewiness, gumminess and firmness while increasing cohesiveness, with maximum resilience at 20% spinach enrichment. Sensory analysis with 21 untrained panellists revealed decreased visual appeal, less preferred taste, odour and overall liking (p &lt; 0.05) with increasing spinach, with no significant difference in texture acceptance, but the 20% enrichment had comparable acceptance to white bread. Enriching staple foods like bread with leafy vegetable waste offers a promising approach for increasing daily vegetable intake.

Background: Clinical work-up for suspected acute coronary syndrome (ACS) is resource intensive. Objectives: This study aimed to develop a machine learning model for digitally phenotyping myocardial injury and infarction and predict 30-day events in suspected ACS patients. Methods: Training and testing data sets, predominantly derived from electronic health records, included suspected ACS patients presenting to 6 and 26 South Australian hospitals, respectively. All index presentations and 30-day death and myocardial infarction (MI) were adjudicated using the Fourth Universal Definition of MI. We developed 2 diagnostic prediction models which phenotype myocardial injury and infarction according to the Fourth UDMI (chronic myocardial injury vs acute myocardial injury patterns, the latter further differentiated into acute non-ischaemic myocardial injury, Types 1 and 2 MI) using eXtreme Gradient Boosting (XGB) and deep-learning (DL). We also developed an event prediction model for risk prediction of 30-day death or MI using XGB. Analyses were performed in Python 3.6. Results: and achieved 95.5% ± 0.2% and 94.6% ± 0.9%, respectively, for differentiating type 1 MI from type 2 MI or acute nonischemic myocardial injury. The 30-day death/MI event prediction model achieved an area under the curve of 88.5% ± 0.5%. Conclusions: Machine learning models can digitally phenotype suspected ACS patients at index presentation and predict subsequent events within 30 days. These models require external validation in a randomized clinical trial to evaluate their impact in clinical practice.

BACKGROUND: Frailty in patients undergoing craniotomy may affect perioperative outcomes. There have been a number of studies published in this field; however, evidence is yet to be summarized in a quantitative review format. We conducted a systematic review and meta-analysis to examine the effects of frailty on perioperative outcomes in patients undergoing craniotomy surgery. METHODS: Our eligibility criteria included adult patients undergoing open cranial surgery. We searched MEDLINE via Ovid SP, EMBASE via Ovid SP, Cochrane Library, and grey literature. We included retrospective and prospective observational studies. Our primary outcome was a composite of complications as per the Clavien-Dindo classification system. We utilized a random-effects model of meta-analysis. We conducted three preplanned subgroup analyses: patients undergoing cranial surgery for tumor surgery only, patients undergoing non-tumor surgery, and patients older than 65 undergoing cranial surgery. We explored sources of heterogeneity through a sensitivity analysis and post hoc analysis. RESULTS: In this review of 63,159 patients, the pooled prevalence of frailty was 46%. The odds ratio of any Clavien-Dindo grade 1-4 complication developing in frail patients compared to non-frail patients was 2.01 [1.90-2.14], with no identifiable heterogeneity and a moderate level of evidence. As per GradePro evidence grading methods, there was low-quality evidence for patients being discharged to a location other than home, length of stay, and increased mortality in frail patients. CONCLUSION: Increased frailty was associated with increased odds of any Clavien-Dindo 1-4 complication. Frailty measurements may be used as an integral component of risk-assessment strategies to improve the quality and value of neurosurgical care for patients undergoing craniotomy surgery. ETHICS AND DISSEMINATION: Formal ethical approval is not needed, as primary data were not collected. SYSTEMATIC REVIEW REGISTRATION: PROSPERO identification number: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=405240.

BACKGROUND: Switching from a conventional to a high-sensitivity cardiac troponin (hs-cTn) assay enables detection of smaller amounts of myocardial damage, but the clinical benefit is unclear. We investigated whether switching to a hs-cTnI assay with a sex-specific 99th centile diagnostic threshold was associated with lower 1-year death or new myocardial infarction (MI) in patients with suspected acute coronary syndrome (ACS). METHODS: This pre-post study included nine tertiary hospitals in Australia. During the pre-hs-cTn period, all hospitals used conventional troponin assays, and during the postperiod, four switched to using hs-cTnI. Participants were ≥20 years old and presenting to emergency departments (EDs) with suspected ACS between March 2011 and November 2015. Outcomes were determined using linked administrative data and compared using Kaplan-Meier and Cox regression analyses. RESULTS: We identified 179 681 consecutive patients (62 (SD 19) years, 47% women), 87 019 (48%) during the preperiod, and 92 662 (52%) during the postperiod. Following the switch to hs-TnI, the proportion of patients diagnosed with new MI was not significantly different (3.9% postperiod vs 4.2% preperiod; p=0.08) while diagnoses of unstable angina were lower (1.5% postperiod vs 2.5% preperiod; p<0.0001). In non-switching jurisdictions, rates of new MI remained stable, while diagnoses of unstable angina increased. Switching to hs-cTnI assay was associated with lower mortality at 30 days (adjusted HR 0.88 (0.82, 0.95)) and 1 year (aHR 0.90 (0.85, 0.94)). The corresponding aHRs for non-switching jurisdictions were not statistically different. CONCLUSION: The use of an hs-cTnI assay in an ED population with suspected ACS was associated with lower mortality at 1 year.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) on host cells, via its spike protein, and transmembrane protease, serine 2 (TMPRSS2) cleaves the spike-ACE2 complex to facilitate virus entry. As rate-limiting steps for virus entry, modulation of ACE2 and/or TMPRSS2 may decrease SARS-CoV-2 infectivity and COVID-19 severity. In silico modeling suggested the natural bioactive flavonoid quercetin can bind to ACE2 and a recent randomized clinical trial demonstrated that oral supplementation with quercetin increased COVID-19 recovery. A range of cultured human cells were assessed for co-expression of ACE2 and TMPRSS2. Immortalized Calu-3 lung cells, cultured and matured at an air-liquid interface (Calu-3-ALIs), were established as the most appropriate. Primary bronchial epithelial cells (PBECs) were obtained from healthy adult males (N = 6) and cultured under submerged conditions to corroborate the outcomes. Upon maturation or reaching 80% confluence, respectively, the Calu-3-ALIs and PBECs were treated with quercetin, and mRNA and protein expression were assessed by droplet digital PCR and ELISA, respectively. SARS-CoV-2 infectivity, and the effects of pre- and co-treatment with quercetin, was assessed by median tissue culture infectious dose assay. Quercetin dose-dependently decreased ACE2 and TMPRSS2 mRNA and protein in both Calu-3-ALIs and PBECs after 4 h, while TMPRSS2 remained suppressed in response to prolonged treatment with lower doses (twice daily for 3 days). Quercetin also acutely decreased ADAM17 mRNA, but not ACE, in Calu-3-ALIs, and this warrants further investigation. Calu-3-ALIs, but not PBECs, were successfully infected with SARS-CoV-2; however, quercetin had no antiviral effect, neither directly nor indirectly through downregulation of ACE2 and TMPRSS2. Calu-3-ALIs were reaffirmed to be an optimal cell model for research into the regulation of ACE2 and TMPRSS2, without the need for prior genetic modification, and will prove valuable in future coronavirus and respiratory infectious disease work. However, our data demonstrate that a significant decrease in the expression of ACE2 and TMPRSS2 by a promising prophylactic candidate may not translate to infection prevention.

BACKGROUND: National stroke clinical quality registries/audits support improvements in stroke care. In a 2016 systematic review, 28 registries were identified. Since 2016 there have been important advances in stroke care, including the development of thrombectomy services. Therefore, we sought to understand whether registries have evolved with these advances in care. The aim of this systematic review was to identify current, hospital-based national stroke registries/audits and describe variables (processes, outcome), methods, funding and governance). METHODS: We searched four databases (21st May 2015 to 1st February 2024), grey literature and stroke organisations' websites. Initially two reviewers screened each citation; when agreement was satisfactory, one of four reviewers screened each citation. The same process was applied to full texts. If there were no new publications from registries identified in the original 2016 review, we contacted the registry leads. We extracted data using predefined categories on country (including income level), clinical/process variables, methods, funding and governance. RESULTS: We found 37 registries from 31 countries (28 high income, four upper-middle income, five lower-middle income) of which 16 had been identified in 2016 and 21 were new. Twenty-two of the same variables were collected by >50% of registries/audits (mostly acute care, including thrombectomy, and secondary prevention), compared with only four variables in 2016. Descriptions of funding, management, methods of consent and data privacy, follow-up, feedback to hospitals, linkage to other datasets and alignment of variables with guidelines were variably reported. Reasons for apparent termination of some registries was unclear. CONCLUSIONS: The total number of stroke registries has increased since 2016, and the number of variables collected has increased, reflecting advances in stroke care. However, some registries appeared to have ceased; the reasons are unclear.

INTRODUCTION: Atrial fibrillation (AF) ablation often involves large-diameter catheters, posing challenges for post-procedure hemostasis and discharge. The impact of Perclose Prostyle vascular closure device (VCD) on time to ambulation and vascular access complications in patients undergoing pulsed field ablation (PFA) is uncertain. METHODS: Patients undergoing PFA for AF with 16.8 French (F) sheaths were randomly assigned in a 1:1 ratio to Prostyle (Abbott Vascular, USA) or standard closure with a figure-of-eight suture (FO8) at a single center in an open-label design. A maximum of three VCDs were allowed. Pre-closure was achieved with deployment at 2 and 10 o'clock positions and a final Prostyle secured the second 6F short sheath. Ultrasound guidance was used in all patients. The primary end point was time to ambulation post-procedure. Secondary end points included major and minor periprocedural adverse events. Follow-up occurred up to 2 weeks post-procedure. RESULTS: Sixty patients were randomized to undergo VCD (30 patients) or F08 suture (30 patients). There were no significant differences in baseline characteristics between groups. Time to ambulation was significantly reduced (215 ± 113 min) in the VCD group compared with the FO8 group (338 ± 71 min; p < 0.001). There were no major peri-procedural adverse events in either group. Rate of minor bleeding was significantly increased in the FO8 group (27%; 8/30) compared with none in the VCD group ((0%; 0/30; p = 0.005)). Rate of manual compression was numerically higher in the FO8 group (33%; 10/30) compared with the VCD group (10%; 3/30; p = 0.057). There were no differences in acute pain score, confidence in walking, overall patient satisfaction, or overall nurse satisfaction between groups. CONCLUSION: In this randomized controlled trial, VCD with Prostyle reduced time to ambulation and reduced minor bleeding in patients undergoing PFA for AF.

This study aimed to develop a low-fructose (< 3 g/serve) carbohydrate (CHO) gel for athletes. Various prototypes with 30 g CHO/serve and differing water content (12%, 21%, 32%, 39% w/v) were created and evaluated for sensory attributes. The final gel contained 62.1 ± 0.2 g CHO/100 g with 0.17% w/w fructose. Endurance athletes (n = 21) underwent a feeding-challenge protocol, ingesting the gel every 20 min during 2 h of running (60% O2max), followed by a 1 h self-paced distance test. Blood glucose increased significantly from baseline (4.0 ± 0.9 vs. 6.6 ± 0.6 mmol/L, p < 0.001) and remained elevated after the distance test (4.9 ± 0.7 mmol/L, p < 0.05). Breath hydrogen levels increased (5 ± 4 ppm, p < 0.05) without substantial CHO malabsorption detected. Gastrointestinal symptoms (GIS) increased during exercise but were mild. The low-fructose CHO gel demonstrated good tolerance, promoting glucose availability without severe GIS or CHO malabsorption.

Importance: Liquid-stored platelets have a shelf-life of 5 to 7 days, limiting availability and resulting in wastage. Objective: To assess the effectiveness and safety of dimethyl sulfoxide-cryopreserved platelets, which have a shelf-life of 2 years, as a treatment for cardiac surgery bleeding. Design, Setting, and Participants: The Cryopreserved vs Liquid Platelets II (CLIP-II) trial was a multicenter, randomized, double-blind, parallel-group noninferiority trial, which enrolled patients between August 2021 and April 2024 at 11 Australian tertiary hospitals, with follow-up completed in July 2024. Patients at high risk of platelet transfusion were eligible. Patients were excluded if they had a history of deep vein thrombosis or pulmonary embolism, were coagulopathic, or were females aged 18 to 55 years who were rhesus D (RhD) negative or of unknown RhD status. Of 879 patients meeting inclusion criteria, 182 were excluded and 285 did not consent, leaving 412. Of these, 388 were randomized and 202 received study platelets. Interventions: Patients received up to 3 units of either group O cryopreserved platelets or conventional liquid-stored platelets, commencing intraoperatively or in the first 24 postoperative hours. Main Outcomes and Measures: The primary outcome was postsurgical chest drain bleeding within the first 24 hours following intensive care unit admission. Noninferiority was defined prospectively as less than 20% greater bleeding in this period. Five secondary and 42 tertiary outcomes were defined a priori. Results: Of the 202 transfused patients (mean [SD] age, 64.4 [13] years; 75.7% male), 61 (30.2%) underwent nonelective surgery. The primary outcome did not differ between groups (605 mL in cryopreserved platelet group vs 535 mL in liquid-stored platelet group; ratio of geometric means [cryopreserved to liquid ratio], 1.13 [95% CI, 0.96-1.34]; P = .07). As the confidence interval includes bleeding exceeding the noninferiority margin, noninferiority was not established. Cryopreserved platelet transfusion was associated with higher intraoperative and total perioperative blood loss (ratio of geometric means [cryopreserved to liquid ratio], 1.42 [95% CI, 1.12-1.80]; 1.31 [95% CI, 1.07-1.60], respectively), and increased red cell, plasma, and cryoprecipitate transfusion. While there were no differences in the incidence of prespecified adverse events, patients receiving cryopreserved platelets experienced longer times to extubation and intensive care unit/hospital discharge (median [IQR] duration of ventilation, 25.5 hours [16.1-77.3] vs 23.6 hours [13.1-52.8]; median [IQR] intensive care unit length of stay, 3.8 days [2.0-6.0] vs 3.0 days [1.9-4.9]; median hospital length of stay, 10.9 days [7.87-17.0] vs 9.1 [6.9-14.9]). Conclusions and Relevance: Cryopreserved platelets did not meet the predefined threshold for noninferiority in hemostatic effectiveness at 24 hours after ICU admission. Additional predefined end points consistently indicated diminished hemostatic effectiveness, although prespecified adverse events were comparable. Trial Registration: ClinicalTrials.gov Identifier: NCT03991481.

BACKGROUND: The Australian College of Critical Care Nurses published the third edition of practice standards (PSs) for specialist critical care nurses in 2015. Higher-education providers currently use these standards to inform critical care curricula; however, how critical care nurses perceive and use PSs in clinical practice is unknown. OBJECTIVES: The objective of this study was to explore critical care nurses' perceptions about the Australian College of Critical Care Nurses PS for specialty critical care nursing, to understand how the PSs are used in clinical practice, and what opportunities exist to support their implementation. METHODS: An exploratory qualitative descriptive design was used. A purposive sampling strategy was used, with 12 critical care specialist nurses consenting to participate in semistructured interviews. The interviews were recorded and transcribed verbatim. Transcripts were analysed thematically using an inductive coding approach. FINDINGS: Three main themes were identified: (i) lack of awareness of the PS; (ii) minimal to no utilisation of the PS in clinical practice and the challenges contributing to this; and (iii) improving the implementation and utilisation of the PS in clinical practice. CONCLUSIONS: There is a significant lack of awareness and utilisation of the PS in clinical practice. To overcome this, increasing recognition, endorsement, and valuation of the PSs to stakeholders at an individual, health service, and legislative level are suggested. Further research is required to establish relevance of the PS in clinical practice and understand how clinicians use the PS to promote and develop critical care nursing.

Inflammation is associated with the pathophysiology of type 2 diabetes and COVID-19. Phytochemicals have the potential to modulate inflammation, expression of SARS-CoV-2 viral entry receptors (angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2)) and glucose transport in the gut. This study assessed the impact of phytochemicals on these processes. We screened 12 phytochemicals alongside 10 pharmaceuticals and three plant extracts, selected for known or hypothesised effects on the SARS-CoV-2 receptors and COVID-19 risk, for their effects on the expression of ACE2 or TMPRSS2 in differentiated Caco-2/TC7 human intestinal epithelial cells. Genistein, apigenin, artemisinin and sulforaphane were the most promising ones, as assessed by the downregulation of TMPRSS2, and thus they were used in subsequent experiments. The cells were then co-stimulated with pro-inflammatory cytokines interleukin-1 beta (IL-1β) and tumour necrosis factor-alpha (TNF-α) for ≤168 h to induce inflammation, which are known to induce multiple pathways, including the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Target gene expression (ACE2, TMPRSS2, SGLT1 (sodium-dependent glucose transporter 1) and GLUT2 (glucose transporter 2)) was measured by droplet digital PCR, while interleukin-1 (IL-6), interleukin-1 (IL-8) and ACE2 proteins were assessed using ELISA in both normal and inflamed cells. IL-1β and TNF-α treatment upregulated ACE2, TMPRSS2 and SGLT1 gene expression. ACE2 increased with the duration of cytokine exposure, coupled with a significant decrease in IL-8, SGLT1 and TMPRSS2 over time. Pearson correlation analysis revealed that the increase in ACE2 was strongly associated with a decrease in IL-8 (r = −0.77, p &lt; 0.01). The regulation of SGLT1 gene expression followed the same pattern as TMPRSS2, implying a common mechanism. Although none of the phytochemicals decreased inflammation-induced IL-8 secretion, genistein normalised inflammation-induced increases in SGLT1 and TMPRSS2. The association between TMPRSS2 and SGLT1 gene expression, which is particularly evident in inflammatory conditions, suggests a common regulatory pathway. Genistein downregulated the inflammation-induced increase in SGLT1 and TMPRSS2, which may help lower the postprandial glycaemic response and COVID-19 risk or severity in healthy individuals and those with metabolic disorders.