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.

Characteristics and Outcomes of Very Elderly Patients Admitted to Intensive Care: A Retrospective Multicenter Cohort Analysis.

OBJECTIVES: To characterize and compare trends in ICU admission, hospital outcomes, and resource utilization for critically ill very elderly patients (≥ 80 yr old) compared with the younger cohort (16-79 yr old). DESIGN: A retrospective multicenter cohort study. SETTING: One-hundred ninety-four ICUs contributing data to the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database between January 2006 and December 2018. PATIENTS: Adult (≥ 16 yr) patients admitted to Australian and New Zealand ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Very elderly patients with a mean ± sd age of 84.8 ± 3.7 years accounted for 14.8% (232,582/1,568,959) of all adult ICU admissions. They had higher comorbid disease burden and illness severity scores compared with the younger cohort. Hospital (15.4% vs 7.8%, p < 0.001) and ICU mortality (8.5% vs 5.2%, p < 0.001) were higher in the very elderly. They stayed fewer days in ICU, but longer in hospital and had more ICU readmissions. Among survivors, a lower proportion of very elderly was discharged home (65.2% vs 82.4%, p < 0.001), and a higher proportion was discharged to chronic care/nursing home facilities (20.1% vs 7.8%, p < 0.001). Although there was no change in the proportion of very elderly ICU admissions over the study period, they showed a greater decline in risk-adjusted mortality (6.3% [95% CI, 5.9%-6.7%] vs 4.0% [95% CI, 3.7%-4.2%] relative reduction per year, p < 0.001) compared with the younger cohort. The mortality of very elderly unplanned ICU admissions improved faster than the younger cohort ( p < 0.001), whereas improvements in mortality among elective surgical ICU admissions were similar in both groups ( p = 0.45). CONCLUSIONS: The proportion of ICU admissions greater than or equal to 80 years old did not change over the 13-year study period. Although their mortality was higher, they showed improved survivorship over time, especially in the unplanned ICU admission subgroup. A higher proportion of survivors were discharged to chronic care facilities.

Critical windows of early-life microbiota disruption on behaviour, neuroimmune function, and neurodevelopment.

Numerous studies have emphasised the importance of the gut microbiota during early life and its role in modulating neurodevelopment and behaviour. Epidemiological studies have shown that early-life antibiotic exposure can increase an individual's risk of developing immune and metabolic diseases. Moreover, preclinical studies have shown that long-term antibiotic-induced microbial disruption in early life can have enduring effects on physiology, brain function and behaviour. However, these studies have not investigated the impact of targeted antibiotic-induced microbiota depletion during critical developmental windows and how this may be related to neurodevelopmental outcomes. Here, we addressed this gap by administering a broad-spectrum oral antibiotic cocktail (ampicillin, gentamicin, vancomycin, and imipenem) to mice during one of three putative critical windows: the postnatal (PN; P2-9), pre-weaning (PreWean; P12-18), or post-weaning (Wean; P21-27) developmental periods and assessed the effects on physiology and behaviour in later life. Our results demonstrate that targeted microbiota disruption during early life has enduring effects into adolescence on the structure and function of the caecal microbiome, especially for antibiotic exposure during the weaning period. Further, we show that microbial disruption in early life selectively alters circulating immune cells and modifies neurophysiology in adolescence, including altered myelin-related gene expression in the prefrontal cortex and altered microglial morphology in the basolateral amygdala. We also observed sex and time-dependent effects of microbiota depletion on anxiety-related behavioural outcomes in adolescence and adulthood. Antibiotic-induced microbial disruption had limited and subtle effects on social behaviour and did not have any significant effects on depressive-like behaviour, short-term working, or recognition memory. Overall, this study highlights the importance of the gut microbiota during critical windows of development and the subtle but long-term effects that microbiota-targeted perturbations can have on brain physiology and behaviour.

Winogradskyella bathintestinalis sp. nov., isolated from the intestine of the deep-sea loosejaw dragonfish, Malacosteus niger.

A novel bacterial strain, APC 3343T, was isolated from the intestine of a deep-sea loosejaw dragon fish, Malacosteus niger, caught at a depth of 1000 m in the Northwest Atlantic Ocean. Cells were aerobic, rod-shaped, yellow/orange-pigmented, non-motile and Gram-negative. Growth of strain APC 3343T was observed at 4-30 °C (optimum, 21-25 °C), pH 5.5-10 (optimum, pH 7-8) and 0.5-8 % (w/v) NaCl (optimum, 2-4 %). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain APC 3343T was most closely related to members of the genus Winogradskyella, with the most closely related type strains being Winogradskyella algae Kr9-9T (98.46 % identity), Winogradskyella damuponensis F081-2T (98.07 %), Winogradskyella eximia CECT 7946T (97.93 %), Winogradskyella litoriviva KMM 6491T (97.79 %) and Winogradskyella endarachnes HL2-2T (97.79 %). Major fatty acids (>10 % of total) were iso-C16 : 0 3-OH, iso-C15 : 0, anteiso-C15 : 0 and iso-C17 : 0 3-OH. The predominant respiratory quinone was menaquinone-6 (MK-6). Polar lipids were phosphatidylethanolamine, three unknown aminolipids and eight unknown lipids. The draft genome sequence was 3.8 Mb in length with a G+C content of 33.43 mol%. Based on the phenotypic characteristics and phylogenetic analysis, strain APC 3343T is deemed to be a novel species of the genus Winogradskyella, and for which the name Winogradskyella bathintestinalis sp. nov. is proposed. The type strain of this species is APC 3343T (=DSM 115832T=NCIMB 15464T).

Osmotic and metabolic responses to cold acclimation and acute cold challenge in a freeze avoidant lizard, Podarcis siculus.

Ectotherms survive exposure to subzero temperatures through freeze tolerance or freeze avoidance. Among vertebrate ectotherms, glucose is commonly used as a cryoprotectant in freeze tolerant strategies and as an osmolyte in freeze avoidant strategies, while also functioning as a metabolic substrate. Whereas some lizard species are capable of both freeze tolerance and freeze avoidance, Podarcis siculus is limited to freeze avoidance through supercooling. We hypothesized that, even in a freeze-avoidant species such as P. siculus, plasma glucose would accumulate with cold acclimation and would increase in response to acute exposure to subzero temperatures. To investigate this, we tested whether plasma glucose concentration and osmolality would increase in response to a subzero cold challenge before and after cold acclimation. In addition, we examined the relationship between metabolic rate, cold acclimation, and glucose by measuring metabolic rate during the cold challenge trials. We found that plasma glucose increased during the cold challenge trials, and that the increase was more pronounced after cold acclimation. However, baseline plasma glucose decreased throughout cold acclimation. Interestingly, total plasma osmolality did not change, and the increase in glucose only slightly altered freezing point depression. Metabolic rate during the cold challenge decreased after cold acclimation, and changes in respiratory exchange ratio suggest an increased relative use of carbohydrates. Overall, our findings demonstrate an important role for glucose in the response of P. siculus to an acute cold challenge, thus adding evidence for glucose as an important molecule for overwintering ectotherms that use freeze avoidant strategies.

Nursing workload and patient-focused outcomes in intensive care: A systematic review.

The aim of this systematic review was to examine the association of nursing workload on patient outcomes in intensive care units. The primary outcome measure was patient mortality, with adverse events (AE), the secondary outcome measures. Electronic search of databases including MEDLINE, CINAHL, Cochrane, EMCARE, Scopus, and Web of Science were performed. Studies were excluded if they were in non-ICU settings, pediatric, neonatal populations, or if the abstract/full text was unavailable. Risk of bias was assessed by the ROBINS-I tool. After screening 4129 articles, 32 studies were identified as meeting inclusion criteria. The majority of included studies were assessed as having a moderate risk of bias. The nursing activities score (NAS) was the most frequently used tool to assess nursing workload. Our systematic review identified that higher nursing workload was associated with patient-focused outcomes, including increased mortality and AE in the intensive care setting. The varied approaches of measuring and reporting nursing workload make it difficult to translate the findings of the impact of nursing workload on patient outcomes in intensive care settings.

Nursing workforce, education, and training challenges to implementing extracorporeal membrane oxygenation services in Australian intensive care units: A qualitative substudy.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) is increasing in the management of critical care patients. ECMO service delivery requires an organisation-supported approach to ensure appropriate resources to deliver training, equipment, capacity, staffing, and the required model of care for quality care delivery. The aim of this nested substudy was to explore challenges specific to nursing staff in ECMO services in Australian intensive care units. METHODS: This was a nested substudy within a qualitative study using semistructured focus group discussions conducted with 83 health professionals, which included 40 nurses. There were 14 focus groups across 14 ECMO centres participating in the binational ECMO (EXCEL) registry of Australia and New Zealand. An inductive thematic analysis focused on the nurse's experiences of the barriers and facilitators for nursing in providing an ECMO service. RESULTS: Four themes emerged relating to the nurse's experience of implementing ECMO services: workforce requirements, workload demands, models of care, and level of experience. The complexity and intensity of caring for ECMO patients may need to be considered an additional factor in the burnout in critical care nurses. Current nursing ratios and responsibilities in critical care need to be considered, with the opportunity for the development of specialist advanced practitioner nursing roles. CONCLUSION: This study highlights the challenges for nursing in providing ECMO services in the intensive care setting. The complexity and intensity of ECMO is challenging and leads to concerns regarding burnout and workforce preparedness. New models of care need to be considered to mitigate the barriers for nursing identified across ECMO centres.

The relationship between nursing skill mix and severity of illness of patients admitted in Australian and New Zealand intensive care units.

BACKGROUND: Critically ill patients in the intensive care environment require an appropriate nursing workforce to improve quality of care and patient outcomes. However, limited information exists as to the relationship between severity of illness and nursing skill mix in the intensive care. OBJECTIVE: The aim of this study was to describe the variation in nursing skill mix across different hospital types and to determine if this was associated with severity of illness of critically ill patients admitted to adult intensive care units (ICUs) in Australia and New Zealand. DESIGN & SETTING: A retrospective cohort study using the Australia and New Zealand Intensive Care Society Adult Patient Database (to provide information on patient demographics, severity of illness, and outcome) and the Critical Care Resources Registry (to provide information on annual nursing staffing levels and hospital type) from July 2014 to June 2020. Four hospital types (metropolitan, private, rural/regional, and tertiary) and three patient groups (elective surgical, emergency surgical, and medical) were examined. MAIN OUTCOME MEASURE: The main outcome measure was the proportion of critical care specialist registered nurses (RNs) expressed as a percentage of the full-time equivalent (FTE) of total RNs working within each ICU each year, as reported annually to the Critical Care Resources Registry. RESULTS: Data were examined for 184 ICUs in Australia and New Zealand. During the 6-year study period, 770 747 patients were admitted to these ICUs. Across Australia and New Zealand, the median percentage of registered nursing FTE with a critical care qualification for each ICU (n = 184) was 59.1% (interquartile range [IQR] = 48.9-71.6). The percentage FTE of critical care specialist RNs was highest in private [63.7% (IQR = 52.6-78.2)] and tertiary ICUs [58.1% (IQR = 51.2-70.2)], followed by metropolitan ICUs [56.0% (IQR = 44.5-68.9)] with the lowest in rural/regional hospitals [55.9% (IQR = 44.9-70.0)]. In ICUs with higher percentage FTE of critical care specialist RNs, patients had higher severity of illness, most notably in tertiary and private ICUs. This relationship was persistent across all hospital types when examining subgroups of emergency surgical and medical patients and in multivariable analysis after adjusting for the type of hospital and relative percentage of each diagnostic group. CONCLUSIONS: In Australian and New Zealand ICUs, the highest acuity patients are cared for by nursing teams with the highest percentage FTE of critical care specialist RNs. The Australian and New Zealand healthcare system has a critical care nursing workforce which scales to meet the acuity of ICU patients across Australia and New Zealand.

Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial.

BACKGROUND: Advanced biliary tract cancer has a poor prognosis. Cisplatin and gemcitabine is the standard first-line chemotherapy regimen, but no robust evidence is available for second-line chemotherapy. The aim of this study was to determine the benefit derived from second-line FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy in advanced biliary tract cancer. METHODS: The ABC-06 clinical trial was a phase 3, open-label, randomised trial done in 20 sites with expertise in managing biliary tract cancer across the UK. Adult patients (aged ≥18 years) who had histologically or cytologically verified locally advanced or metastatic biliary tract cancer (including cholangiocarcinoma and gallbladder or ampullary carcinoma) with documented radiological disease progression to first-line cisplatin and gemcitabine chemotherapy and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (1:1) centrally to active symptom control (ASC) and FOLFOX or ASC alone. FOLFOX chemotherapy was administered intravenously every 2 weeks for a maximum of 12 cycles (oxaliplatin 85 mg/m2, L-folinic acid 175 mg [or folinic acid 350 mg], fluorouracil 400 mg/m2 [bolus], and fluorouracil 2400 mg/m2 as a 46-h continuous intravenous infusion). Randomisation was done following a minimisation algorithm using platinum sensitivity, serum albumin concentration, and stage as stratification factors. The primary endpoint was overall survival, assessed in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. The study is complete and the final results are reported. This trial is registered with ClinicalTrials.gov, NCT01926236, and EudraCT, 2013-001812-30. FINDINGS: Between March 27, 2014, and Jan 4, 2018, 162 patients were enrolled and randomly assigned to ASC plus FOLFOX (n=81) or ASC alone (n=81). Median follow-up was 21·7 months (IQR 17·2-30·8). Overall survival was significantly longer in the ASC plus FOLFOX group than in the ASC alone group, with a median overall survival of 6·2 months (95% CI 5·4-7·6) in the ASC plus FOLFOX group versus 5·3 months (4·1-5·8) in the ASC alone group (adjusted hazard ratio 0·69 [95% CI 0·50-0·97]; p=0·031). The overall survival rate in the ASC alone group was 35·5% (95% CI 25·2-46·0) at 6 months and 11·4% (5·6-19·5) at 12 months, compared with 50·6% (39·3-60·9) at 6 months and 25·9% (17·0-35·8) at 12 months in the ASC plus FOLFOX group. Grade 3-5 adverse events were reported in 42 (52%) of 81 patients in the ASC alone group and 56 (69%) of 81 patients in the ASC plus FOLFOX group, including three chemotherapy-related deaths (one each due to infection, acute kidney injury, and febrile neutropenia). The most frequently reported grade 3-5 FOLFOX-related adverse events were neutropenia (ten [12%] patients), fatigue or lethargy (nine [11%] patients), and infection (eight [10%] patients). INTERPRETATION: The addition of FOLFOX to ASC improved median overall survival in patients with advanced biliary tract cancer after progression on cisplatin and gemcitabine, with a clinically meaningful increase in 6-month and 12-month overall survival rates. To our knowledge, this trial is the first prospective, randomised study providing reliable, high-quality evidence to allow an informed discussion with patients of the potential benefits and risks from second-line FOLFOX chemotherapy in advanced biliary tract cancer. Based on these findings, FOLFOX should become standard-of-care chemotherapy in second-line treatment for advanced biliary tract cancer and the reference regimen for further clinical trials. FUNDING: Cancer Research UK, StandUpToCancer, AMMF (The UK Cholangiocarcinoma Charity), and The Christie Charity, with additional funding from The Cholangiocarcinoma Foundation and the Conquer Cancer Foundation Young Investigator Award for translational research.

Biopsy for advanced hepatocellular carcinoma: results of a multicentre UK audit.

BACKGROUND: Advanced hepatocellular carcinoma (HCC) is commonly diagnosed using non-invasive radiological criteria (NIRC) defined by the European Association for the Study of the Liver or the American Association for the Study of Liver Diseases. In 2017, The National Institute for Clinical Excellence mandated histological confirmation of disease to authorise the use of sorafenib in the UK. METHODS: This was a prospective multicentre audit in which patients suitable for sorafenib were identified at multidisciplinary meetings. The primary analysis cohort (PAC) was defined by the presence of Child-Pugh class A liver disease and performance status 0-2. Clinical, radiological and histological data were reported locally and collected on a standardised case report form. RESULTS: Eleven centres reported 418 cases, of which 361 comprised the PAC. Overall, 76% had chronic liver disease and 66% were cirrhotic. The diagnostic imaging was computed tomography in 71%, magnetic resonance imaging in 27% and 2% had both. Pre-existing histology was available in 45 patients and 270 underwent a new biopsy, which confirmed HCC in 93.4%. Alternative histological diagnoses included cholangiocarcinoma (CC) and combined HCC-CC. In cirrhotic patients, NIRC criteria had a sensitivity of 65.4% and a positive predictive value of 91.4% to detect HCC. Two patients (0.7%) experienced mild post-biopsy bleeding. CONCLUSION: The diagnostic biopsy is safe and feasible for most patients eligible for systemic therapy.

Risk of COVID-19 death in cancer patients: an analysis from Guy's Cancer Centre and King's College Hospital in London.

BACKGROUND: Using an updated dataset with more patients and extended follow-up, we further established cancer patient characteristics associated with COVID-19 death. METHODS: Data on all cancer patients with a positive reverse transcription-polymerase chain reaction swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Guy's Cancer Centre and King's College Hospital between 29 February and 31 July 2020 was used. Cox proportional hazards regression was performed to identify which factors were associated with COVID-19 mortality. RESULTS: Three hundred and six SARS-CoV-2-positive cancer patients were included. Seventy-one had mild/moderate and 29% had severe COVID-19. Seventy-two patients died of COVID-19 (24%), of whom 35 died <7 days. Male sex [hazard ratio (HR): 1.97 (95% confidence interval (CI): 1.15-3.38)], Asian ethnicity [3.42 (1. 59-7.35)], haematological cancer [2.03 (1.16-3.56)] and a cancer diagnosis for >2-5 years [2.81 (1.41-5.59)] or ≥5 years were associated with an increased mortality. Age >60 years and raised C-reactive protein (CRP) were also associated with COVID-19 death. Haematological cancer, a longer-established cancer diagnosis, dyspnoea at diagnosis and raised CRP were indicative of early COVID-19-related death in cancer patients (<7 days from diagnosis). CONCLUSIONS: Findings further substantiate evidence for increased risk of COVID-19 mortality for male and Asian cancer patients, and those with haematological malignancies or a cancer diagnosis >2 years. These factors should be accounted for when making clinical decisions for cancer patients.

Cost-utility analysis of selective internal radiation therapy with Y-90 resin microspheres in hepatocellular carcinoma.

Background: The study assessed the cost-utility of selective internal radiation therapy (SIRT) with Y-90 resin microspheres versus sorafenib in UK patients with unresectable hepatocellular carcinoma ineligible for transarterial chemoembolization. Materials & methods: A lifetime partitioned survival model was developed for patients with low tumor burden (≤25%) and good liver function (albumin-bilirubin grade 1). Efficacy, safety and quality of life data were from a European Phase III randomized controlled trial and published studies. Resource use was from registries and clinical surveys. Results: Discounted quality-adjusted life-years were 1.982 and 1.381, and discounted total costs were £29,143 and 30,927, for SIRT and sorafenib, respectively. Conclusion: SIRT has the potential to be a dominant (more efficacious/less costly) or cost-effective alternative to sorafenib in patients with unresectable hepatocellular carcinoma.

Evaluation of a laparoscopic abdominal simulator assessment to test readiness for laparoscopic ovariectomy in live dogs.

OBJECTIVE: To predict readiness for laparoscopic ovariectomy of live dogs on the basis of performance on a high-fidelity laparoscopic abdominal simulator and to determine interrater reliability of the assessment. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Seventeen fourth-year veterinary students. METHODS: After a standardized laparoscopic training course, each participant performed a laparoscopic ovariectomy with a simulator. This performance was scored in real time by two evaluators using a rubric. Participants achieving a score of 112 of 160 performed a laparoscopic ovariectomy in a live dog, supervised by an instructor in the room. Two evaluators scored video recordings of each procedure using the rubric. Participants' opinions about the simulator were collected with a survey. RESULTS: All participants scored above the threshold (range, 126-151) and successfully completed laparoscopic ovariectomy in a live dog, with an average of 10 of 17 participants requiring verbal guidance and 5 of 17 participants requiring intervention from the instructor. Interrater concordance was excellent for the rubrics used to score performance on the simulator (R = 0.91) and in vivo (R = 0.81). All participants agreed that the simulator should be used to assess trainee readiness prior to surgery in a live dog. CONCLUSION: Participants achieving a score of at least 126 of 160 on the simulator were able to perform a laparoscopic ovariectomy in a live dog under supervision. The scoring system for the simulator had excellent interrater concordance. CLINICAL SIGNIFICANCE: This simulator and scoring system can be used in laparoscopic training programs to assess readiness for progression to the operative setting.

The Australian and New Zealand Clinician Educator Network (ANZCEN) Unconference: What's an unconference and how can it develop communities of practice?

The Australian and New Zealand Clinician Educator Network (ANZCEN) is a collaborative interprofessional group developed to promote the development of education in critical care healthcare practice. In November 2018, 45 critical care practitioners met at the first ANZCEN Unconference. In an unconference, the participants drive the agenda, and learning occurs from the active process of engaging in a community of practice. The aim of this unconference was to develop an innovative approach to learning through a collaborative framework with interprofessional representation across critical care specialties. Four key themes were identified in the unconference as drivers of interprofessional critical care educational priorities: interprofessional learning, workplace learning, faculty development, research, and scholarship. In this discussion paper, we describe our experiences organizing, participating in, and evaluating an unconference, and we examine its usefulness as a medium for promoting the interprofessional learning agenda in critical care. We hope that the processes outlined in this discussion paper will provide a useful resource for other clinicians who are considering developing an unconference. Finally, we argue that the unconference offers a unique and important model for future education of critical care practitioners where the emphasis on collaboration and communication through interprofessional learning and practice will be required to improve health outcomes and promote a patient-centered model of care.

Hyperoxia in patients with cardiogenic shock after myocardial infarction supported with venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (V-A ECMO) improves perfusion and oxygenation in patients with cardiogenic shock. However, it can also result in supranormal oxygen exposure. Recent evidence suggests hyperoxia may be harmful, particularly in critically ill patients. The aim of this study was to describe oxygen exposure in patients receiving V-A ECMO after acute myocardial infarction and to investigate the association between hyperoxia and in-hospital mortality. METHODS AND DESIGN: We conducted a retrospective, cohort study of consecutive patients receiving V-A ECMO at a single tertiary level ECMO centre. We compared the mean and peak arterial oxygen tensions over the first 72 h after V-A ECMO initiation (n = 30) with those from a convenience sample of patients treated with an intra-aortic balloon pump (IABP) (n = 30) for cardiogenic shock. RESULTS: Sixty patients admitted between January 2012 and March 2018 were included in the study. Patients on V-A ECMO had significantly higher arterial oxygen tensions during the first three days than those with an IABP, at 0-24 h; V-A ECMO: 286.51 mmHg (135.76) vs IABP: 103.48 mmHg (15.22), p < 0.01.Thirteen of 30 (44.8%) patients in the V-A ECMO cohort manifested extreme hyperoxia (PaO2 ≥300 mmHg) in the first 24 hrs, compared with none in the IABP population. Within the V-A ECMO group, there was no significant association between extreme hyperoxia and in-hospital mortality (P = 0.19), duration of mechanical ventilation (P = 0.63), or troponin levels (P = 0.16) in the first 24 hrs. CONCLUSION: Severe hyperoxia is common in patients receiving V-A ECMO after acute myocardial infarction, and this continues for at least 72 h. We found no association between extreme hyperoxia and clinical outcomes.

Short-chain fatty acids and microbiota metabolites attenuate ghrelin receptor signaling.

The gastrointestinal microbiota is emerging as a unique and inexhaustible source for metabolites with potential to modulate G-protein coupled receptors (GPCRs). The ghrelin receptor [growth hormone secretagogue receptor (GHSR)-1a] is a GPCR expressed throughout both the gut and the brain and plays a crucial role in maintaining energy balance, metabolism, and the central modulation of food intake, motivation, reward, and mood. To date, few studies have investigated the potential of the gastrointestinal microbiota and its metabolites to modulate GPCR signaling. Here we investigate the ability of short-chain fatty acids (SCFAs), lactate, and different bacterial strains, including Bifidobacterium and Lactobacillus genera, to modulate GHSR-1a signaling. We identify, for what is to our knowledge the first time, a potent effect of microbiota-derived metabolites on GHSR-1a signaling with potential significant consequences for host metabolism and physiology. We show that SCFAs, lactate, and bacterial supernatants are able to attenuate ghrelin-mediated signaling through the GHSR-1a. We suggest a novel route of communication between the gut microbiota and the host via modulation of GHSR-1a receptor signaling. Together, this highlights the emerging therapeutic potential in the exploration of the microbiota metabolome in the specific targeting of key GPCRs, with pleiotropic actions that span both the CNS and periphery.-Torres-Fuentes, C., Golubeva, A. V., Zhdanov, A. V., Wallace, S., Arboleya, S., Papkovsky, D. B., El Aidy, S., Ross, P., Roy, B. L., Stanton, C., Dinan, T. G., Cryan, J. F., Schellekens, H. Short-chain fatty acids and microbiota metabolites attenuate ghrelin receptor signaling.

Effects of a polysaccharide-rich extract derived from Irish-sourced Laminaria digitata on the composition and metabolic activity of the human gut microbiota using an in vitro colonic model.

BACKGROUND: Brown seaweeds are known to be a rich source of fiber with the presence of several non-digestible polysaccharides including laminarin, fucoidan and alginate. These individual polysaccharides have previously been shown to favorably alter the gut microbiota composition and activity albeit the effect of the collective brown seaweed fiber component on the microbiota remains to be determined. METHODS: This study investigated the effect of a crude polysaccharide-rich extract obtained from Laminaria digitata (CE) and a depolymerized CE extract (DE) on the gut microbiota composition and metabolism using an in vitro fecal batch culture model though metagenomic compositional analysis using 16S rRNA FLX amplicon pyrosequencing and short-chain fatty acid (SCFA) analysis using GC-FID. RESULTS: Selective culture analysis showed no significant changes in cultured lactobacilli or bifidobacteria between the CE or DE and the cellulose-negative control at any time point measured (0, 5, 10, 24, 36, 48 h). Following metagenomic analysis, the CE and DE significantly altered the relative abundance of several families including Lachnospiraceae and genera including Streptococcus, Ruminococcus and Parabacteroides of human fecal bacterial populations in comparison to cellulose after 24 h. The concentrations of acetic acid, propionic acid, butyric acid and total SCFA were significantly higher for both the CE and DE compared to cellulose after 10, 24, 36 and 48 h fermentation (p < 0.05). Furthermore, the acetate:propionate ratio was significantly reduced (p < 0.05) for both CD and DE following 24, 36 and 48 h fermentation. CONCLUSION: The microbiota-associated metabolic and compositional changes noted provide initial indication of putative beneficial health benefits of L. digitata in vitro; however, research is needed to clarify if L. digitata-derived fiber can favorably alter the gut microbiota and confer health benefits in vivo.

Tumor burden and liver function in HCC patient selection for selective internal radiation therapy: SARAH post-hoc study.

Aim: To determine whether a liver tumor burden ≤25% and well-preserved liver function (albumin-bilirubin grade 1) are appropriate criteria for identifying patients with unresectable hepatocellular carcinoma who may benefit from selective internal radiation therapy (SIRT) using 90yttrium resin microspheres versus sorafenib. Patients & methods: Post-hoc analysis of patients in the intention-to-treat population of the SARAH trial (SIRT vs sorafenib) with ≤25% tumor burden and albumin-bilirubin grade 1. Primary end point: overall survival. Results: Median overall survival was 21.9 months (95% CI: 15.2-32.5, n = 37) with SIRT and 17.0 months (11.6-20.8, n = 48) with sorafenib (hazard ratios: 0.73; 95% CI: 0.44-1.21; p = 0.22). Conclusion: A combination of good liver function and low tumor burden may be relevant for selection of hepatocellular carcinoma patients for SIRT.

NUC-1031/cisplatin versus gemcitabine/cisplatin in untreated locally advanced/metastatic biliary tract cancer (NuTide:121).

Gemcitabine/cisplatin is standard of care for first-line treatment of patients with advanced biliary tract cancer (aBTC); new treatments are needed. NUC-1031 is designed to overcome key cancer resistance mechanisms associated with gemcitabine. The tolerability/efficacy signal of NUC-1031/cisplatin in the Phase Ib ABC-08 study suggested that this combination may represent a more efficacious therapy than gemcitabine/cisplatin for patients with aBTC, leading to initiation of the global NuTide:121 study which will include 828 patients ≥18 years with untreated histologically/cytologically-confirmed aBTC (including cholangiocarcinoma, gallbladder or ampullary cancer); randomized (1:1) to NUC-1031 (725 mg/m2)/cisplatin (25 mg/m2) or gemcitabine (1000 mg/m2)/cisplatin (25 mg/m2), on days 1/8, Q21-days. Primary objectives are overall survival and objective response rate. Secondary objectives: progression-free survival, safety, pharmacokinetics, patient-reported quality of life and correlative studies. (Investigational new drug (IND) number: 139058, European Clinical Trials database: EudraCT Number 2019-001025-28, ClinicalTrials.gov identifier: NCT04163900).