Gut Microbiome in Children with Congenital Heart Disease After Cardiopulmonary Bypass Surgery (GuMiBear Study).

The gut microbiome of infants with congenital heart disease (CHD) undergoing cardiopulmonary bypass surgery (CPB) is at risk of profound alteration. The aim of this study was to examine the gut microbiome pre- and post-bypass surgery to explore potential implications of altered gut biodiversity. A prospective cohort study involving infants with CHD who underwent CPB was performed. Faecal samples were collected from infants alongside the collection of demographic and clinical data in order to examine gut microbiome changes before and after surgery. 16S rRNA sequencing analysis was performed on DNA isolated from stool samples to determine changes in gut microbiome composition. Thirty-three patients were recruited, with samples from thirteen of these available for final analysis. Compared with healthy, matched controls, at a genus level, pre-operative samples for infants with CHD demonstrated a higher relative abundance of Escherichia-Shigella (31% vs 2-6%) and a lower relative abundance of Bifidobacterium (13% vs 40-60%). In post-operative samples, the relative abundance of Escherichia-Shigella (35%), Enterococcus (11%), Akkermansia (6%), and Staphylococcus (5%) were higher than pre-op samples. One infant developed post-operative necrotising-enterocolitis (NEC). They displayed a marked abundance of the Enterococcus (93%) genus pre-operatively. This study demonstrates that infants with CHD have an altered gut microbiome when compared with healthy controls and there might be a possible link between an abundance of virulent species and NEC.

Engineering Toxoplasma gondii secretion systems for intracellular delivery of multiple large therapeutic proteins to neurons.

Delivering macromolecules across biological barriers such as the blood-brain barrier limits their application in vivo. Previous work has demonstrated that Toxoplasma gondii, a parasite that naturally travels from the human gut to the central nervous system (CNS), can deliver proteins to host cells. Here we engineered T. gondii's endogenous secretion systems, the rhoptries and dense granules, to deliver multiple large (>100 kDa) therapeutic proteins into neurons via translational fusions to toxofilin and GRA16. We demonstrate delivery in cultured cells, brain organoids and in vivo, and probe protein activity using imaging, pull-down assays, scRNA-seq and fluorescent reporters. We demonstrate robust delivery after intraperitoneal administration in mice and characterize 3D distribution throughout the brain. As proof of concept, we demonstrate GRA16-mediated brain delivery of the MeCP2 protein, a putative therapeutic target for Rett syndrome. By characterizing the potential and current limitations of the system, we aim to guide future improvements that will be required for broader application.

The impact of nursing workforce skill-mix on patient outcomes in intensive care units in Victoria, Australia.

Objective: This article aims to examine the impact of nursing workforce skill-mix (percentage of critical care registered nurses [CCRN]) in the intensive care unit (ICU) during a patient's stay. Design: Registry linked cohort study of the Australian and New Zealand Intensive Care Society Adult Patient Database and the Critical Health Resources Information System using real-time nursing workforce data. Settings: Fifteen public and 5 private hospital ICUs in Victoria, Australia. Participants: There were 16,618 adult patients admitted between 1 December 2021 and 30 September 2022. Main outcome measures: Primary outcome: in-hospital mortality. Secondary outcomes: in-ICU mortality, development of delirium, pressure injury, duration of stay in-ICU and hospital, after-hours discharge from ICU and readmission to ICU. Results: In total, 6563 (39.5%) patients were cared for in ICUs with >75% CCRN, 7695 (46.3%) in ICUs with 50-75% CCRN, and 2360 (14.2%) in ICUs with <50% CCRN. In-hospital mortality was 534 (8.1%) vs. 859 (11.2%) vs. 252 (10.7%) respectively. After adjusting for confounders, patients cared for in ICUs with 50-75% CCRN (adjusted OR 1.21 [95% CI 1.02-1.45]) were more likely to die compared to patients in ICUs with >75% CCRN. A similar but non-significant trend was seen in ICUs with <50% CCRN (adjusted OR 1.21 [95% CI 0.94-1.55]), when compared to patients in ICUs with >75% CCRN. In-ICU mortality, delirium, pressure injuries, after-hours discharge and ICU length of stay were lower in ICUs with CCRN>75%. Conclusion: The nursing skill-mix in ICU impacts outcomes and should be routinely monitored. Health system regulators, hospital administrators and ICU leaders should ensure nursing workforce planning and education align with these findings to maximise patient outcomes.

Genome plasticity shapes the ecology and evolution of Phocaeicola dorei and Phocaeicola vulgatus.

Phocaeicola dorei and Phocaeicola vulgatus are very common and abundant members of the human gut microbiome and play an important role in the infant gut microbiome. These species are closely related and often confused for one another; yet, their genome comparison, interspecific diversity, and evolutionary relationships have not been studied in detail so far. Here, we perform phylogenetic analysis and comparative genomic analyses of these two Phocaeicola species. We report that P. dorei has a larger genome yet a smaller pan-genome than P. vulgatus. We found that this is likely because P. vulgatus is more plastic than P. dorei, with a larger repertoire of genetic mobile elements and fewer anti-phage defense systems. We also found that P. dorei directly descends from a clade of P. vulgatus¸ and experienced genome expansion through genetic drift and horizontal gene transfer. Overall, P. dorei and P. vulgatus have very different functional and carbohydrate utilisation profiles, hinting at different ecological strategies, yet they present similar antimicrobial resistance profiles.

Safety and Preliminary Efficacy of Pembrolizumab Following Transarterial Chemoembolization for Hepatocellular Carcinoma: The PETAL Phase Ib Study.

PURPOSE: Transarterial chemoembolization (TACE) may prime adaptive immunity and enhance immunotherapy efficacy. PETAL evaluated safety, preliminary activity of TACE plus pembrolizumab and explored mechanisms of efficacy. PATIENTS AND METHODS: Patients with liver-confined hepatocellular carcinoma (HCC) were planned to receive up to two rounds of TACE followed by pembrolizumab 200 mg every 21 days commencing 30 days post-TACE until disease progression or unacceptable toxicity for up to 1 year. Primary endpoint was safety, with assessment window of 21 days from pembrolizumab initiation. Secondary endpoints included progression-free survival (PFS) and evaluation of tumor and host determinants of response. RESULTS: Fifteen patients were included in the safety and efficacy population: 73% had nonviral cirrhosis; median age was 72 years. Child-Pugh class was A in 14 patients. Median tumor size was 4 cm. Ten patients (67%) received pembrolizumab after one TACE; 5 patients after two (33%). Pembrolizumab yielded no synergistic toxicity nor dose-limiting toxicities post-TACE. Treatment-related adverse events occurred in 93% of patients, most commonly skin rash (40%), fatigue, and diarrhea (27%). After a median follow-up of 38.5 months, objective response rate 12 weeks post-TACE was 53%. PFS rate at 12 weeks was 93% and median PFS was 8.95 months [95% confidence interval (CI): 7.30-NE (not estimable)]. Median duration of response was 7.3 months (95% CI: 6.3-8.3). Median overall survival was 33.5 months (95% CI: 11.6-NE). Dynamic changes in peripheral T-cell subsets, circulating tumor DNA, serum metabolites, and in stool bacterial profiles highlight potential mechanisms of action of multimodal therapy. CONCLUSIONS: TACE plus pembrolizumab was tolerable with no evidence of synergistic toxicity, encouraging further clinical development of immunotherapy alongside TACE.

Planococcus notacanthi sp. nov., isolated from the skin of a deep-sea snub-nosed spiny eel.

A novel bacterial strain, APC 4016T, was previously isolated from the skin of a snub-nosed spiny eel, Notacanthus chemnitzii, from a depth of 1000 m in the northern Atlantic Ocean. Cells were aerobic, cocci, motile, Gram-positive to Gram-variable staining, and gave rise to orange-pigmented colonies. Growth occurred at 4-40 °C (optimum, 25-28 °C), pH 5.5-12 (optimum, pH 7-7.5), and 0-12 % (w/v) NaCl (optimum, 1 %). 16S rRNA gene phylogenetic analysis confirmed that strain APC 4016T belonged to the genus Planococcus and was most closely related to Planococcus okeanokoites IFO 12536T (98.98 % 16S similarity). However, digital DNA-DNA hybridization and average nucleotide identity values between these two strains were low, at 20.1 and 83.8 %, respectively. Major (>10 %) cellular fatty acids of strain APC 4016T were iso-C14 : 0, anteiso-C15 : 0 and C16 : 1-ω-Alc. The predominant respiratory quinones were menaquinones 5, 6, 7 and 8. The major cellular polar lipids were phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine, and three unknown lipids were also present. The draft genome sequence is 3.6 Mb with a G+C content of 45.25 mol%. This strain was previously shown to have antimicrobial activity and to encode bacteriocin and secondary metabolite biosynthetic gene clusters. Based on the phylogenetic analysis and its distinct phenotypic characteristics, strain APC 4016T is deemed to represent a novel species of the genus Planococcus, and for which the name Planococcus notacanthi sp. nov. is proposed. The type strain of this species is APC 4016T (=DSM 115753T=NCIMB 15463T).

An exploration of intensive care nurses' perceptions of workload in providing extracorporeal membrane oxygenation (ECMO) support: A descriptive qualitative study.

BACKGROUND: There is increasing use of extracorporeal membrane oxygenation (ECMO) in intensive care, where nurses provide the majority of the required ongoing care of cannulas, circuit, and console. Limited evidence currently exists that details nursing perspectives, experiences, and challenges with workload in the provision of ECMO care. OBJECTIVE: The objective of this study was to investigate intensive care nurses' perceptions of workload in providing specialist ECMO therapy and care in a high-volume ECMO centre. METHODS: The study used a qualitative descriptive methodology through semistructured interviews. Data were analysed using an inductive thematic analysis approach following Braun and Clarke's iterative process. This study was conducted in an intensive care unit within an Australian public, quaternary, university-affiliated hospital, which provides specialist state-wide service for ECMO. FINDINGS: Thirty ECMO-specialist trained intensive care nurses were interviewed. This study identified three key themes: (i) opportunity; (ii) knowledge and responsibilities; and (iii) systems and structures impacting on intensive care nurses' workload in providing ECMO supportive therapy. CONCLUSIONS: Intensive care nurses require advanced clinical and critical thinking skills. Intensive care nurses are motivated and engaged to learn and acquire ECMO skills and competency as part of their ongoing professional development. Providing bedside ECMO management requires constant monitoring and surveillance from nurses to care for the one of the most critically unwell patient populations in the intensive care unit setting. As such, ECMO nursing services require a suitably trained and educated workforce of intensive care trained nurses. ECMO services provide clinical development opportunities for nurses, increase their scope of practice, and create advanced practice-specialist roles.

Factors that influence the implementation of innovation in aged care: a scoping review.

OBJECTIVE: The objective of this scoping review is to identify factors that influence the implementation of innovation in aged care. INTRODUCTION: Aged care is a dynamic sector experiencing rapid change. Implementation of innovations in aged care has received relatively little research attention compared to health care. INCLUSION CRITERIA: This review included studies of any design, that examined the implementation of innovations in aged care settings. METHODS: Searches were conducted in MEDLINE, CINAHL, AgeLine, and ProQuest Social Sciences Premium Collection for studies published between January 1, 2012 and December 31, 2022. The titles and abstracts of retrieved citations were screened by two independent reviewers. Full-text articles were screened by one reviewer to determine inclusion. Data were extracted in NVivo using a tool developed by the research team. Factors that influenced implementation were inductively coded, interpreted, and grouped into categories in a series of workshops. RESULTS: Of the 2530 studies that were screened, 193 were included. Of the included papers, the majority (74%) related to residential aged care, 28% used an implementation theory or framework, and 15% involved consumers. Five key categories of factors influencing implementation were identified: organizational context including resourcing and culture; people's attitudes and capabilities; relationships between people; the intervention and its appropriateness; and implementation actions such as stakeholder engagement and implementation strategies. CONCLUSIONS: Our findings can be used to develop practical resources to support implementation efforts, and highlight the importance of resourcing for successful implementation. Attention to community-based aged care, and greater engagement with theory and community is needed to promote research rigor, relevance and applicability.