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Abstract Background and Aim Long‐term human albumin (HA) infusions improve survival in cirrhotic patients with diuretic resistant ascites. We aimed to determine whether there is a significant benefit in a more unwell real‐world cohort. Methods This is a single‐center retrospective cohort study. Patients received outpatient HA between April 2017 and June 2021. Inclusion criteria were age ≥18 years, cirrhosis with ascites, and received at least 1 month of HA. Patients with significant comorbidities and ongoing alcohol use were not excluded. Outcomes assessed were transjugular intrahepatic portosystemic shunt (TIPS)/transplant‐free survival (TTFS), and biochemical and prognostic outcomes. Results Twenty‐four patients were included. Median age was 59.5 years. Seven were female (29.2%). Etiology included were alcohol (50%), non‐alcoholic steatohepatitis (16.7%), and viral/alcohol (12.5%). Median model for end‐stage liver disease‐sodium (MELD‐Na) was 18.5, with Child–Pugh scores (CPS) A (4.2%), B (50%), and C (45.8%). Improvements in serum sodium (P = 0.014), albumin (P = 0.003), and CPS (P = 0.017) were observed. Reduction in hospitalizations (P = 0.001), particularly portal hypertensive related admissions was observed (relative risk 0.39; 95% confidence interval [CI] 0.21–0.69, P = 0.003), needed to treat 2.09 (95% CI 1.25–3.67). There was a reduction in total paracentesis requirements (P = 0.005). On multivariate analysis, type 2 diabetes mellitus significantly increased risk of TIPS/transplant/death (hazard ratio 6.16; 95% CI 1.23–30.84, P = 0.027). Median TTFS improved in patients with a change in MELD‐Na ≤1 at 1 month: 29.4 months versus 7.7 months (P = 0.011). Conclusion Outpatient HA infusions decrease portal hypertensive related hospital admissions, improve serum sodium, albumin levels, and CPS. Type 2 diabetes mellitus and change in MELD‐Na score help discriminate those likely to benefit most.

The management of early-stage hepatocellular carcinoma (HCC) is complex, with multiple treatment strategies available. There is a paucity of literature regarding variations in the patterns of care and outcomes between transplant and non-transplant centres. We conducted this real-world multi-centre cohort study in two liver cancer referral centres with an integrated liver transplant program and an additional eight non-transplant HCC referral centres across Australia to identify variation in patterns of care and key survival outcomes. Patients with stage Barcelona Clinic Liver Cancer (BCLC) 0/A HCC, first diagnosed between 1 January 2016 and 31 December 2020, who were managed at a participating site, were included in the study. Patients were excluded if they had a history of prior HCC or if they received upfront liver transplantation. A total of 887 patients were included in the study, with 433 patients managed at a liver cancer centre with a transplant program (LTC) and 454 patients managed at a non-transplant centre (NTC). Management at an LTC did not significantly predict allocation to resection (adjusted OR 0.75, 95% CI 0.50 to 1.11, p = 0.148). However, in those not receiving resection, LTC and NTC patients were systematically managed differently, with LTC patients five times less likely to receive upfront ablation than NTC patients (adjusted OR 0.19, 95% CI 0.13 to 0.28, p < 0.001), even after adjusting for tumour burden, as well as for age, gender, liver disease aetiology, liver disease severity, and medical comorbidities. LTCs exhibited significantly higher proportions of patients undergoing TACE for every tumour burden category, including those with a single tumour measuring 2 cm or less (p < 0.001). Using multivariable Cox proportional hazards analysis, management at a transplant centre was associated with reduced all-cause mortality (adjusted HR 0.71, 95% CI 0.51 to 0.98, p = 0.036), and competing-risk regression analysis, considering liver transplant as a competing event, demonstrated a similar reduction in risk (adjusted HR 0.70, 95% CI 0.50 to 0.99, p = 0.041), suggesting that the reduced risk of death is not fully explained by higher rates of transplantation. Our study highlights systematic differences in HCC care between large volume liver transplant centres and other sites, which has not previously been well-described. Further work is needed to better define the reasons for differences in treatment allocation and to aim to minimise unwarranted treatment variation to maximise patient outcomes across Australia.

The optimal treatment approach in very-early and early-stage hepatocellular carcinoma (HCC) is not precisely defined, and there is ambiguity in the literature around the comparative efficacy of surgical resection versus ablation as curative therapies for limited disease. We performed this real-world propensity-matched, multi-centre cohort study to assess for differences in survival outcomes between those undergoing resection and those receiving ablation. Patients with Barcelona Clinic Liver Cancer (BCLC) 0/A HCC first diagnosed between 1 January 2016 and 31 December 2020 who received ablation or resection as initial treatment were included in the study. A total of 450 patients were included in the study from 10 major liver centres including two transplant centres. Following propensity score matching using key covariates, 156 patients were available for analysis with 78 in each group. Patients who underwent resection had significantly improved overall survival (log-rank test p = 0.023) and local recurrence-free survival (log rank test p = 0.027) compared to those who received ablation. Based on real-world data, our study supports the use of surgical resection in preference to ablation as first-line curative therapy in appropriately selected BCLC 0/A HCC patients.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2009.01.044 Byline: Hannah R. Nicholas (a), Jonathan Hodgkin (b) Keywords: Caenorhabditis elegans; Hox gene; Rectal epithelium; Infection; Morphogenesis Abstract: Members of the Hox gene family encode transcription factors that specify positional identity along the anterior-posterior axis of nearly all metazoans. One among the Caenorhabditis elegans Hox genes is egl-5. A deletion allele of egl-5 was isolated in a screen for animals which fail to develop swollen tails when exposed to the bacterial pathogen Microbacterium nematophilum. We show that compromised rectal development, which occurs as a result of loss of egl-5 function, results in a failure of rectal epithelial cells to express the ERK MAP kinase mpk-1, which was previously shown to mediate tail-swelling in response to bacterial infection. Tissue-specific rescue experiments demonstrated that egl-5 and mpk-1 act autonomously in rectal cells in the morphological response. The weak egl-5 allele (n1439), which does not compromise rectal development, fails to affect tail-swelling. We find that this allele carries an inserted repeat element [approximately equal to]13.8 kb upstream of the egl-5 open reading frame, which specifically disrupts the cell-specific expression of this gene in HSN egg-laying neurons. Together these findings extend the complexity of regulation and function of Hox genes in C. elegans and demonstrate the importance of their tissue-specific expression for correct development and response to infection. Author Affiliation: (a) School of Molecular and Microbial Biosciences, University of Sydney, NSW, 2006, Australia (b) Genetics Unit, Department of Biochemistry, University of Oxford, South Parks Rd, Oxford, OX1 3QU, UK Article History: Received 30 April 2008; Revised 29 December 2008; Accepted 9 January 2009

Interactions with bacteria play a major role in immune responses, ecology, and evolution of all animals, but they have been neglected until recently in the case of C. elegans. We report a genetic investigation of the interaction of C. elegans with the nematode-specific pathogen Microbacterium nematophilum, which colonizes the rectum and causes distinctive tail swelling in its host. A total of 121 mutants with altered response to infection were isolated from selections or screens for a bacterially unswollen (Bus) phenotype, using both chemical and transposon mutagenesis. Some of these correspond to known genes, affecting either bacterial adhesion or colonization (srf-2, srf-3, srf-5) or host swelling response (sur-2, egl-5). Most mutants define 15 new genes (bus-1-bus-6, bus-8 bus-10, bus-12-bus-18). The majority of these mutants exhibit little or no rectal infection when challenged with the pathogen and are probably altered in surface properties such that the bacteria can no longer infect worms. A number have corresponding alterations in lectin staining and cuticle fragility. Most of the uninfectable mutants grow better than wild type in the presence of the pathogen, but the sur-2 mutant is hypersensitive, indicating that the tail-swelling response is associated with a specific defense mechanism against this pathogen.

Brain development requires precise regulation of axon outgrowth, guidance and termination by multiple signaling and adhesion molecules. How the expression of these neurodevelopmental regulators is transcriptionally controlled is poorly understood. The Caenorhabditis elegans SMD motor neurons terminate axon outgrowth upon sexual maturity and partially retract their axons during early adulthood. Here we show that C-terminal binding protein 1 (CTBP-1), a transcriptional corepressor, is required for correct SMD axonal development. Loss of CTBP-1 causes multiple defects in SMD axon development: premature outgrowth, defective guidance, delayed termination and absence of retraction. CTBP-1 controls SMD axon guidance by repressing the expression of SAX-7, an L1 cell adhesion molecule (L1CAM). CTBP-1-regulated repression is crucial because deregulated SAX-7/L1CAM causes severely aberrant SMD axons.We found that axonal defects caused by deregulated SAX-7/L1CAM are dependent on a distinct L1CAM, called LAD-2, which itself plays a parallel role in SMD axon guidance. Our results reveal that harmonization of L1CAM expression controls the development and maturation of a single neuron. [ABSTRACT FROM AUTHOR]