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Lucy Gracen,1 Melanie Aikebuse,2,3 Babak Sarraf,2– 4 Steven M McPhail,5 Anthony W Russell,6 James O’Beirne,7 Katharine M Irvine,8 Suzanne Williams,9 Patricia C Valery,4,* Elizabeth E Powell2– 4,* 1Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia; 2Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia; 3Centre for Liver Disease Research, Faculty of Medicine, Translational Research Institute, The University of Queensland, Woolloongabba, QLD, Australia; 4QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; 5Australian Centre for Health Services Innovation School of Public Health, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD, Australia; 6Endocrinology and Diabetes, the Alfred Hospital, Melbourne, VIC, Australia; 7Department of Gastroenterology and Hepatology, Sunshine Coast University Hospital, Birtinya, QLD, Australia; 8Mater Research, Translational Research Institute, Brisbane, QLD, Australia; 9Inala Primary Care General Practice, Inala, QLD, Australia*These authors contributed equally to this workCorrespondence: Elizabeth E Powell, Centre for Liver Disease Research, Faculty of Medicine, Translational, Research Institute, The University of Queensland, Level 5, West Wing, 37, Kent Street, Woolloongabba, Brisbane, QLD, 4102, Australia, Tel +61 412 014 337, Email e.powell@uq.edu.auBackground: Although clinical guidelines endorse screening for metabolic dysfunction-associated steatotic liver disease (MASLD) with advanced fibrosis in people with type 2 diabetes (T2D), the feasibility of and barriers and considerations relevant to implementing this approach in the community remain unclear.Methods: Sequential adults with T2D attending selected community clinics during 2021– 2023 were invited to receive a “liver health check” (n=543). A further 95 participants were referred directly from their general practitioner (GP) or self-referred to the study. A total of 302 participants underwent a point of care assessment of hepatic steatosis and stiffness (FibroScan) and were advised to see their GP to discuss the results. “Template” letters containing key results, their interpretation and advice about management of cardiometabolic risk, patient follow-up and referral criteria, were sent to participants’ GPs.Results: Referral to a tertiary liver clinic was advised in GP letters for 45 (15%) participants with an increased risk of clinically significant fibrosis (liver stiffness measurement ≥ 8), 15 participants with ‘red flags’ (eg splenomegaly, thrombocytopenia) and 2 with unsuccessful FibroScan examinations. A referral from GPs to the liver clinic was received for 27 (44%) of these 62 participants. Approximately 90% of GPs rated the “template” letters favourably on a Likert rating scale.Conclusion: The low rate of participation in the “liver health check” and liver clinic referral reflects a real-world scenario and may stem from societal under-recognition and engagement with MASLD, competing health priorities or under-appreciation of the link between liver fibrosis severity and mortality risk. Further studies need to address strategies to enhance participation in liver health assessments and determine their impact on liver-related morbidity/mortality and overall survival.Keywords: NAFLD, primary care, chronic liver disease, FibroScan

Abstract Background Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. Methods Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. Discussion The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. Trial registration anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Objectives Responding to prior research findings that lack of knowledge about their disease impacted patients’ quality of life, the objective of this study was to identify and prioritise information gaps about hypersensitivity pneumonitis (HP) from the perspective of patients living with the disease.Design This study used the nominal group technique, a semiquantitative and qualitative method to identify stakeholder priorities.Setting Virtual group sessions were conducted in an academic medical centre in the USA.Participants 21 patients diagnosed with HP participated in this study. Participants were eligible if they spoke English and had access to the internet and were excluded if they had cognitive impairment.Results The patient statements were grouped into seven themes that were prioritised by participants in the following order: (1) natural history and prognosis; (2) current treatment options and therapeutic research; (3) epidemiology and aetiology of HP; (4) living well with HP; (5) origin and management of symptoms; (6) identifying and mitigating exposures and (7) methods of educating patients, clinicians and others about HP.Conclusions This study provides an understanding of patients’ prioritisation of knowledge gaps in HP to inform targeted educational interventions and provide avenues for future research.

Abstract Background Liver disease is an important contributor to the mortality gap between First Nations Peoples and non-Indigenous Australian adults. Despite a high burden of metabolic comorbidities among First Nations Peoples, data about the epidemiology of metabolic dysfunction-associated steatotic liver disease (MASLD) in this population is scarce. Methods A retrospective analysis of all adults hospitalized with MASLD or metabolic dysfunction-associated steatohepatitis (MASH) with/without cirrhosis during 2007–2019 in the state of Queensland was performed. Patients were followed from the first admission with MASLD/MASH (identified based on validated algorithms) to decompensated cirrhosis and overall mortality. We explored differences according to Indigenous status using Multivariable Cox regression. Findings 439 First Nations Peoples and 7,547 non-Indigenous Australians were followed for a median of 4.6 years (interquartile range 2.7–7.2). Overall, women were overrepresented, but more so in the First Nations cohort (72.7% vs. 57.0%, p

Abstract Background and Aim Metabolic dysfunction‐associated steatotic liver disease (MASLD) is associated with an increased risk of extrahepatic morbidity. We compared the incidence of cancers in adults admitted to Queensland hospitals with MASLD with that for the Queensland population and examined the association between cirrhosis and type 2 diabetes and the development of extrahepatic cancers. Methods In this retrospective study, we identified all cancers (Queensland Cancer Registry) after the first hospitalization with MASLD during Jul‐2007 to Dec‐2019, estimated age‐standardized incidence (ASI) of cancers, and compared that with the ASI in the Queensland population (incidence rate ratios [IRR]). Among the MASLD cohort, we examined the association between diabetes and cancer risk (Cox regression). Median follow‐up was 3.8 years (54 204 person‐years). Results Totally 1104 new cancers were diagnosed in 1018 patients (8.9% of 9771 non‐cirrhotic and 1712 adults with cirrhosis). The ASI (all cancers) of 1668.2 per 100 000 person‐years in men (95% CI 1523.7–1827.4) and 1284.0 per 100 000 person‐years in women (95% CI 1169.6–1408.2) was 2‐fold higher than that of the Queensland population (IRR = 1.94, 95% CI 1.75–2.16 and IRR = 1.99, 95% CI 1.78–2.22, respectively). Incidence of stomach cancer, unknown primary, and pancreas was 3‐ to 5‐fold higher compared to the general population (all P

Quantitative reconstructions of past continental climates are vital for understanding contemporary and past climate change. Branched glycerol dialkyl glycerol tetraethers (brGDGTs) are unique bacterial lipids that have been proposed as universal paleothermometers due to their correlation with temperature in modern settings. Thus, brGDGTs may serve as a crucial paleotemperature proxy for understanding past climate variations and improving regional climate projections, especially in critical but under constrained regions. That said, complications can arise in their application due to varying source contributions (e.g., soils vs. peats vs. lacustrine). As such, this study investigates brGDGT distributions in Chilean lake surface sediments and corresponding watershed soils to determine the source of brGDGTs to lake sediments. Global datasets of brGDGTs in lake sediments and soils were additionally compiled for comparison. Distinct brGDGT distributions in Chilean lakes and soils indicate minimal bias from soil inputs to the lacustrine sediments as well as in situ lacustrine production of brGDGTs, which supports the use of brGDGTs in lake sediments as reliable paleotemperature proxies in the region. The ΣIIIa/ΣIIa ratio, initially promising as a brGDGT source indicator in marine settings, shows global complexities in lacustrine settings, challenging the establishment of universal thresholds for source apportionment. That said, we show that the ratio can be successfully applied in Chilean lake surface sediments. Direct comparisons with watershed soils and further research are crucial for discerning brGDGT sources in lake sediments and improving paleotemperature reconstructions on regional and global scales moving forward. Overall, this study contributes valuable insights into brGDGT variability, essential for accurate paleoreconstructions.

Abstract Background In Australia, the overall prevalence of liver disease is increasing. Maximising uptake of community screening programmes by understanding patient preferences is integral to developing consumer-centred care models for liver disease. Discrete choice experiments (DCEs) are widely used to elicit preferences for various healthcare services. Attribute development is a vital component of a well-designed DCE and should be described in sufficient detail for others to assess the validity of outcomes. Hence, this study aimed to create a list of potential attributes and levels which can be used in a DCE study to elicit preferences for chronic liver disease screening programmes. Methods Key attributes were developed through a multi-stage, mixed methods design. Focus groups were held with consumers and health care providers on attributes of community screening programmes for liver disease. Stakeholders then prioritised attributes generated from the focus group in order of importance via an online prioritisation survey. The outcomes of the prioritisation exercise were then reviewed and refined by an expert panel to ensure clinically meaningful levels and relevance for a DCE survey. Results Fifteen attributes were generated during the focus group sessions deemed necessary to design liver disease screening services. Outcomes of the prioritisation exercise and expert panel stages recognised five attributes, with three levels each, for inclusion in a DCE survey to elicit consumer preferences for community screening for liver disease. This study also highlights broader social issues such as the stigma around liver disease that require careful consideration by policy makers when designing or implementing a liver screening programme. Conclusions The attributes and levels identified will inform future DCE surveys to understand consumer preferences for community screening programmes for liver disease. In addition, the outcomes will help inform the implementation of the LOCATE-NAFLD programme in real-world practice, and could be relevant for other liver and non-liver related chronic disease screening programmes.

This prospective, community-based, active surveillance study aimed to report the incidence of moderate, severe, and serious adverse events (AEs) after chiropractic (n = 100) / physiotherapist (n = 50) visit in offices throughout North America between October-2015 and December-2017. Three content-validated questionnaires were used to collect AE information: two completed by the patient (pre-treatment [T0] and 2-7 days post-treatment [T2]) and one completed by the provider immediately post-treatment [T1]. Any new or worsened symptom was considered an AE and further classified as mild, moderate, severe or serious. From the 42 participating providers (31 chiropractors; 11 physiotherapists), 3819 patient visits had complete T0 and T1 assessments. The patients were on average 50±18 years of age and 62.5% females. Neck/back pain was the most common presenting condition (70.0%) with 24.3% of patients reporting no condition/preventative care. From the patients visits with a complete T2 assessment (n = 2136 patient visits, 55.9%), 21.3% reported an AE, of which: 7.9% were mild, 6.2% moderate, 3.7% severe, 1.5% serious, and 2.0% had missing severity rating. The most common symptoms reported with moderate or higher severity were discomfort/pain, stiffness, difficulty walking and headache. This study provides valuable information for patients and providers regarding incidence and severity of AEs following patient visits in multiple community-based professions. These findings can be used to inform patients of what AEs may occur and future research opportunities can focus on mitigating common AEs.

Background Epineurium acts as a barrier to protect nerves from injury and maintains its structural and functional integrity. A device was developed to mimic the native structure of epineurium. The aim of this study was to evaluate its biological characteristics and clinical performance in the reconstruction of upper extremity peripheral nerves.

Abstract Viral infections modulate bacterial metabolism and ecology. Here, we investigated the hypothesis that viruses influence the ecology of purple and green sulfur bacteria in anoxic and sulfidic lakes, analogs of euxinic oceans in the geologic past. By screening metagenomes from lake sediments and water column, in addition to publicly-available genomes of cultured purple and green sulfur bacteria, we identified almost 300 high and medium-quality viral genomes. Viruses carrying the gene psbA, encoding the small subunit of photosystem II protein D1, were ubiquitous, suggesting viral interference with the light reactions of sulfur oxidizing autotrophs. Viruses predicted to infect these autotrophs also encoded auxiliary metabolic genes for reductive sulfur assimilation as cysteine, pigment production, and carbon fixation. These observations show that viruses have the genomic potential to modulate the production of metabolic markers of phototrophic sulfur bacteria that are used to identify photic zone euxinia in the geologic past.

Introduction and Objectives: Among people with type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD) is very common and has an increased risk of clinically significant liver disease. The use of sodium-glucose co-transporter 2 (SGLT2i) inhibitors and glucagon-like peptide-1 (GLP-1a) receptor agonists is endorsed to reduce major cardiovascular events and/or progression of chronic kidney disease. Their prevalence of use in people with T2D and co-existent NAFLD remains unclear. We sought to determine the prevalence of use of these medications at two different time periods, and their association with prevalence of clinically significant liver disease. Materials and Methods: Consecutive people with type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) were recruited from diabetes clinics between Jun-2021 and Jun-2022 (‘current’ cohort). Liver stiffness measurements (LSM) using FibroScan were performed. Medication data were collected prospectively at recruitment and verified with the dispensing pharmacy or general practitioner medical records. Data for a historical cohort with NAFLD and T2D recruited from the same clinics during 2015–2017 (‘historical’ cohort) were available. Logistic regression was used to evaluate factors associated with LSM

Levels of iron and iron-related proteins including ferritin are higher in the lung tissue and lavage fluid of individuals with chronic obstructive pulmonary disease (COPD), when compared to healthy controls. Whether more iron in the extracellular milieu of the lung associates with distinct clinical phenotypes of COPD, including increased exacerbation susceptibility, is unknown. We measured iron and ferritin levels in the bronchoalveolar lavage fluid (BALF) of participants enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD (SPIROMICS) bronchoscopy sub-study (n = 195). BALF Iron parameters were compared to systemic markers of iron availability and tested for association with FEV1 % predicted and exacerbation frequency. Exacerbations were modelled using a zero-inflated negative binomial model using age, sex, smoking, and FEV1 % predicted as clinical covariates. BALF iron and ferritin were higher in participants with COPD and in smokers without COPD when compared to non-smoker control participants but did not correlate with systemic iron markers. BALF ferritin and iron were elevated in participants who had COPD exacerbations, with a 2-fold increase in BALF ferritin and iron conveying a 24% and 2-fold increase in exacerbation risk, respectively. Similar associations were not observed with plasma ferritin. Increased airway iron levels may be representative of a distinct pathobiological phenomenon that results in more frequent COPD exacerbation events, contributing to disease progression in these individuals.

Abstract Risk prediction models are frequently used to identify individuals at risk of developing hypertension. This study evaluates different machine learning algorithms and compares their predictive performance with the conventional Cox proportional hazards (PH) model to predict hypertension incidence using survival data. This study analyzed 18,322 participants on 24 candidate features from the large Alberta’s Tomorrow Project (ATP) to develop different prediction models. To select the top features, we applied five feature selection methods, including two filter-based: a univariate Cox p-value and C-index; two embedded-based: random survival forest and least absolute shrinkage and selection operator (Lasso); and one constraint-based: the statistically equivalent signature (SES). Five machine learning algorithms were developed to predict hypertension incidence: penalized regression Ridge, Lasso, Elastic Net (EN), random survival forest (RSF), and gradient boosting (GB), along with the conventional Cox PH model. The predictive performance of the models was assessed using C-index. The performance of machine learning algorithms was observed, similar to the conventional Cox PH model. Average C-indexes were 0.78, 0.78, 0.78, 0.76, 0.76, and 0.77 for Ridge, Lasso, EN, RSF, GB and Cox PH, respectively. Important features associated with each model were also presented. Our study findings demonstrate little predictive performance difference between machine learning algorithms and the conventional Cox PH regression model in predicting hypertension incidence. In a moderate dataset with a reasonable number of features, conventional regression-based models perform similar to machine learning algorithms with good predictive accuracy.

Plain English summary Person-centred care (PCC) is a model of care where patient needs and preferences are included in decisions about care and treatment. To improve PCC in primary care in Alberta, Canada, we plan to use person-centred quality indicators (PC-QIs). Using PC-QIs involves surveying patients about their care experiences and using this information to make improvements. For example, if 20% of patients do not feel they are getting enough information, the clinic may create a checklist for the providers so information is not missed. We engaged a panel of 11 people, including patients, family doctors, and staff who support quality improvement in clinics across the province to decide together which PC-QIs primary care clinics in Alberta should use. We also asked the panel to decide the most important strategies that would make using the PC-QIs more successful. The panel chose PC-QIs related to: patient and caregiver involvement in decisions about care and treatment, a trusting relationship with the healthcare provider, having health information technology to support PCC, partnering with communities in healthcare, and the patient’s overall experience. The most important strategies were: developing partnerships among people working in primary care in Alberta, discussing their needs and common efforts for improving PCC, engaging “champions,” and securing funding that would be needed. Finally, we asked the panelists to share their experiences with participating in this process. Panelists found the process useful and that their input was valued. Most panelists would also like to continue to work together to put the PC-QIs into practice.

Abstract Although there are several established international guidelines on the management of hepatocellular carcinoma (HCC), there is limited information detailing specific indicators of good quality care. The aim of this study was to develop a core set of quality indicators (QIs) to underpin the management of HCC. We undertook a modified, two‐round, Delphi consensus study comprising a working group and experts involved in the management of HCC as well as consumer representatives. QIs were derived from an extensive review of the literature. The role of the participants was to identify the most important and measurable QIs for inclusion in an HCC clinical quality registry. From an initial 94 QIs, 40 were proposed to the participants. Of these, 23 QIs ultimately met the inclusion criteria and were included in the final set. This included (a) nine related to the initial diagnosis and staging, including timing to diagnosis, required baseline clinical and laboratory assessments, prior surveillance for HCC, diagnostic imaging and pathology, tumor staging, and multidisciplinary care; (b) thirteen related to treatment and management, including role of antiviral therapy, timing to treatment, localized ablation and locoregional therapy, surgery, transplantation, systemic therapy, method of response assessment, and supportive care; and (c) one outcome assessment related to surgical mortality. Conclusion: We identified a core set of nationally agreed measurable QIs for the diagnosis, staging, and management of HCC. The adherence to these best practice QIs may lead to system‐level improvement in quality of care and, ultimately, improvement in patient outcomes, including survival.

Joseph Gerard O’Beirne,1 Konstantinos Chlapoutakis,2 Ustun Aydingoz3 1Department of Orthopaedics, University Hospital Waterford, Waterford, Ireland; 2Vioapeikonisi Imaging Lab, Heraklion – Crete, Greece; 3Department of Radiology, Hacettepe University School of Medicine, Ankara, TurkeyCorrespondence: Joseph Gerard O’Beirne, Email jgobeirne@gmail.com