Background: Sepsis remains the leading cause of death in intensive care units. Sepsis is characterised by an inability of the immune system to resolve an infection leading to hypotension and multi-organ dysfunction. We discovered that the brain can suppress innate immune responses to inflammatory stimuli via the splanchnic sympathetic nerves.

Aims: To determine the effects of bilateral splanchnic
sympathetic nerve denervation on blood pressure, plasma cytokines, bacterial clearance and clinical state in sheep with established Gram-negative sepsis.

Methods: Conscious Merino ewes received an intravenous infusion of Escherichia coli for 30-h (1 × 10⁹ colony forming units/mL/h) to induce bacteremia. At 24-h, sheep were randomised to have bilaterally surgically implanted snares anaesthetised and pulled to induce splanchnic-denervation (N = 10), or not (sham; N = 9).

Results: Splanchnic-denervation did not affect mean arterial pressure compared with sham-treatment at 30-h of bacteremia. Splanchnic-denervation increased the plasma concentration of pro-inflammatory cytokine interleukin-6 (9.2 ± 2.5 vs. 3.8 ± 0.3 ng/mL, P Group = 0.031) at 25-h and reduced blood bacterial counts (2.31 ± 0.45 vs. 3.45 ± 0.11 log₁₀ [CFU/mL + 1], P Group = 0.027) at 26-h compared to sham-treatment. There was a sustained improvement in clinical status, characterised by reduced respiratory rate (P Group = 0.024) and increased cumulative water consumption (P Group = 0.008) in splanchnic-denervation compared with sham-treatment.

Conclusion: In Gram-negative bacteremia, interrupting splanchnic sympathetic nerve activity increased plasma interleukin-6, accelerated bacterial clearance, and improved clinical state without inducing hypotension. These findings suggest that splanchnic neural manipulation is a potential target for pharmacological or non-pharmacological interventions.

Background: Haemoadsoprtion is a form of extracorporeal blood purification aimed at removing harmful cells or pathogens and has emerged as an adjunct intervention for sepsis in intensive care units (ICUs). However, it may also cause cardiovascular haemodynamic instability and unintentional removal of antimicrobial drugs, potentially offsetting its therapeutic benefits. Evidence in this area is scarce, and the existing data suggest that drug removal varies depending on the specific drug and cartridges used for the procedure.
Aim: To evaluate the cardiovascular safety and the removal of two widely used antibiotics, meropenem and piperacillin, in a clinically relevant sheep model of haemoadsorption.
Methods: Healthy adult sheep (n=6) received 2 g of meropenem, and 4 g of piperacillin intravenously over 30 minutes, followed by haemoadsorption with a HA380 cartridge at a blood flow rate of 120 mL/min for 4 hours. Blood pressure and heart rate were monitored before and during the procedure. The sorbent-based removal ratio, clearance, and mass removal were calculated at multiple time points.
Results: Mean arterial pressure and heart rate remained stable during hamoadsorption. The sorbent-based removal ratio of meropenem decreased from 95.4% (SD 1.8) at 10 minutes to less than 20% at 4-hours of haemoadsorption. Its cumulative sorbent-based mass removal was 386.6 mg (SD 78.8) over 4 hours with 65.6% (SD 7.1) occurring in the first 60 minutes. In contrast, the sorbent-based removal ratio of piperacillin decreased more gradually from 98.4% (SD 0.6) at 10 minutes to 37.4% (SD 7.2) at 4 hours. Its cumulative sorbent-based mass removal was 647.4 mg (SD 191.3) over 4 hours with 63.4% (SD 4.2) occurring in the first 60 minutes. The overall sorbent-based clearance of piperacillin was significantly greater than meropenem (Pgroup<0.0001).
Conclusion: Haemoadsorption using the HA380 cartridge was haemodynamically safe and achieved a very high adsorption of both drugs at the initiation of the procedure, followed by a progressive decline in sorbent-based removal ratio and clearance. These findings suggest that dose adjustments, potentially increasing by 15–25%, may be necessary to avoid underdosing during haemoadsorption in patients. This study provides critical insights for optimizing antibiotic therapy during haemoadsorption in ICUs.

Background and Aim: The gut microbiota is pivotal in linking diet to cardiovascular disease (CVD). Gut microbiota can produce beneficial metabolites like short-chain fatty acids (SCFAs) through the fermentation of dietary fibre. Nonetheless, the mechanisms driving the relationship between the host and gut microbiome in CVD development remain largely unknown. To address this, we utilized faecal metaproteomics, a novel technique that simultaneously analyses human and microbial protein expression in the gut.
Method: Metaproteomics data from 63 faecal samples of healthy participants and 26 faecal samples from patients with heart failure with preserved ejection fraction (HFpEF) were generated by mass spectrometry. Unsupervised learning was employed to identify clusters based on the expression profiles of human proteins. Pathway analyses were performed to explore functional differences between these clusters. Additionally, we conducted a comparative analysis of paired cross-sectional data, including ambulatory blood pressure monitoring, dietary intake, and medical and demographic information, to further characterise these clusters. A random forest model was subsequently trained using the microbial protein profiles of healthy participants and then applied to the metaproteomics data from HFpEF patients.
Results: Unsupervised clustering based on human proteome data revealed two distinct clusters with different CVD risk profiles—identified as low-risk and high-risk groups. The high-risk group exhibited higher blood pressure (mean±SD, low-risk: 109±15mmHg vs high-risk: 117±17mmHg, P=0.035) and lower dietary potassium (median[Q1, Q3], low-risk: 3987[3508,4507] mg/day vs high risk: 3128[2805,3700] mg/day, P=0.021) and fibre (low-risk: 31±8g/day vs high-risk: 23±7g/day, P=0.022) consumption in men. In the human proteome, the low-risk group showed reduced levels of angiotensin-converting enzymes (CTSD and CTSG) and inflammatory proteins like LCN2. In the microbial proteome, the low-risk group had elevated expression of acetate kinase and phosphate acetyltransferase, involved in SCFA production, particularly by fibre-fermenting bacteria. Furthermore, the microbial protein profiles identified by unsupervised machine learning could predict clinical outcomes in patients with HFpEF.
Conclusion: Through unsupervised clustering of human and microbial proteomics, we identified two groups with distinct cardiovascular risks. These differences highlight the complex interplay between diet, gut microbiota, and cardiovascular health, emphasising the necessity for advanced models to better understand the multifactorial risk factors contributing to cardiovascular disease.

Aim
Various blood pressure (BP) measurement methods are available, including clinic, home, 24-hour, kiosk and cuffless BP monitoring. However, many Australians report never or infrequently measuring their BP. In-depth qualitative studies on consumer attitudes towards different measurement methods are needed, which was the aim of this study.

Methods
Australian adults who participated in a home BP measurement study were purposively sampled for semi-structured interviews. The interview data were then thematically analysed.

Results
We interviewed 29 participants (55% female) aged 61±12.8 years. All reported measuring their BP at a clinic and at home; 13 performed 24-hour ambulatory BP monitoring; six measured BP at a kiosk; and two used cuffless BP devices.
Regarding clinic BP, participants found the process routine and not bothersome. A good rapport with their doctors strongly influenced their satisfaction with clinic BP measurements. Some participants preferred clinic BP as they valued instant feedback from their doctors. Most participants preferred measuring their BP at home due to convenience and the number of measurements they could take. Some believed the home environment to be an ideal situation to measure BP. Attitudes towards 24-hour ambulatory BP measurement varied widely. Several reported severe dislike and discomfort, with one participant stating, “I can't see how [being] stressed by having this nasty machine stuck to you can give you accurate readings”. Others had no issues, and thought it was “not that intrusive”. For measuring BP at a kiosk, accuracy and privacy were concerns since the devices were often in open areas. A couple of participants thought it was a hassle to enter additional information when they only wanted to measure BP. Some participants expressed interest in trying a kiosk BP machine while others were not interested as they “have got a machine at home”. For cuffless BP technology, most participants showed interest but had no experience using cuffless devices. Accuracy and costs were key considerations.

Conclusions
We identified diverse consumer attitudes towards different BP measurement methods. Overall, most consumers preferred home and clinic BP measurements, while ambulatory and kiosk BP monitoring were less preferred. Consumers were interested in cuffless methods, pending reports on accuracy.