Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study.

Background: Transarterial chemoembolisation (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolisation; however, median progression-free survival is still approximately 7 months. We aimed to assess whether adding durvalumab, with or without bevacizumab, might improve progression-free survival.

Methods: In this multiregional, randomised, double-blind, placebo-controlled, phase 3 study (EMERALD-1), adults aged 18 years or older with unresectable hepatocellular carcinoma amenable to embolisation, an Eastern Cooperative Oncology Group performance status of 0 or 1 at enrolment, and at least one measurable intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours (RECIST) were enrolled at 157 medical sites including research centres and general and specialist hospitals in 18 countries.

Risk factors associated with 30-day mortality following COVID-19 infection in patients receiving kidney replacement therapy in Australian and New Zealand.

Background And Aims: The COVID-19 pandemic impacted greatest among patients with pre-existing chronic health conditions, including chronic kidney disease. This retrospective cohort study aimed to investigate the 30-day mortality of patients receiving kidney replacement therapy (KRT) after infection with COVID-19, living in Australia and New Zealand between 2020 and 2022, including patients on haemodialysis (HD), peritoneal dialysis (PD) and renal transplant (KT) recipients.

Methods: This is a retrospective cohort study using data from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA).

Adenomas from individuals with pathogenic biallelic variants in the MUTYH and NTHL1 genes demonstrate base excision repair tumour mutational signature profiles similar to colorectal cancers, expanding potential diagnostic and variant classification applications.

Background: Colorectal cancers (CRCs) from people with biallelic germline likely pathogenic/pathogenic variants in MUTYH or NTHL1 exhibit specific single base substitution (SBS) mutational signatures, namely combined SBS18 and SBS36 (SBS18+SBS36), and SBS30, respectively. The aim was to determine if adenomas from biallelic cases demonstrated these mutational signatures at diagnostic levels.

Methods: Whole-exome sequencing of FFPE tissue and matched blood-derived DNA was performed on 9 adenomas and 15 CRCs from 13 biallelic MUTYH cases, on 7 adenomas and 2 CRCs from 5 biallelic NTHL1 cases and on 27 adenomas and 26 CRCs from 46 non-hereditary (sporadic) participants.

Mind the gap in kidney care: Translating what we know into what we do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do.

A phase Ia study of a novel anti-HER2 antibody-drug conjugate GQ1001 in patients with previously treated HER2 positive advanced solid tumors.

Background: A novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate (ADC) GQ1001 was assessed in patients with previously treated HER2 positive advanced solid tumors in a global multi-center phase Ia dose escalation trial.

Methods: In this phase Ia trial, a modified 3 + 3 study design was adopted during dose escalation phase. Eligible patients were enrolled, and GQ1001 monotherapy was administered intravenously every 3 weeks.

Surgery for Olecranon Fractures in the Elderly (SOFIE): Results of the SOFIE Randomized Controlled Trial.

Background: The financial and resource burden of management of olecranon fractures in the elderly is likely to increase with an aging population. There is limited evidence guiding treatment choice in this cohort. This study aimed to determine whether operative treatment of displaced olecranon fractures in elderly patients provides superior 12-month functional outcomes compared to nonoperative treatment.

Superstable lipid vacuoles endow cartilage with its shape and biomechanics.

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis.

Cardiovascular, kidney and safety outcomes with canagliflozin in older adults: A combined analysis from the CANVAS Program and CREDENCE trial.

Aim: SGLT2 inhibitors may be underused in older adults with type 2 diabetes due to concerns about safety and tolerability. This pooled analysis of the CANVAS Program and CREDENCE trial examined the efficacy and safety of canagliflozin according to age.

Methods: Pooled individual participant data from the CANVAS Program (n = 10 142) and CREDENCE trial (n = 4401) were analysed by baseline age (<65 years, 65 to <75 years, and ≥75 years).

Mitral valve replacement versus repair for severe mitral regurgitation in patients with reduced left ventricular ejection fraction.

Objective: This study compares early and long-term outcomes following mitral valve (MV) repair and replacement in patients with mitral regurgitation (MR) and reduced left ventricular ejection fraction (LVEF).

Methods: Patients with primary or secondary MR and LVEF <50% who underwent MV replacement or repair (with/without atrial septal defect closure and/or atrial fibrillation ablation) between 2005 and 2017 at our center were retrospectively analyzed using unadjusted and propensity score matching techniques (42 pairs).

Results: A total of 356 patients with either primary (n = 162 [45.

Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial.

Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy.

Spatial mapping of the HCC landscape identifies unique intratumoral perivascular-immune neighborhoods.

Background: HCC develops in the context of chronic inflammation; however, the opposing roles the immune system plays in both the development and control of tumors are not fully understood. Mapping immune cell interactions across the distinct tissue regions could provide greater insight into the role individual immune populations have within tumors.

Methods: A 39-parameter imaging mass cytometry panel was optimized with markers targeting immune cells, stromal cells, endothelial cells, hepatocytes, and tumor cells.

Comparing predictive risk to actual presence of coronary atherosclerosis on coronary computed tomography angiography.

Background: There is limited data showing the predictive accuracy of traditional cardiovascular risk scores (CVRS) to predict asymptomatic coronary artery disease (CAD) determined by coronary computed tomography angiography (CCTA).

Methods: Asymptomatic individuals without known CAD undergoing a screening CCTA and sufficient data to calculate their CVRS, were extracted retrospectively. Atherosclerosis was extracted using natural language processing of the CCTA report, including the coronary artery calcium score (CACS) and the extent and severity of CAD.

Real-World Persistence and Effectiveness of Upadacitinib versus Other Janus Kinase Inhibitors and Tumor Necrosis Factor Inhibitors in Australian Patients with Rheumatoid Arthritis.

Introduction: This study sought to describe treatment patterns, persistence, and effectiveness of upadacitinib (UPA) alone and compared to other Janus kinase inhibitors (JAKis) or tumor necrosis factor inhibitors (TNFis) in patients with rheumatoid arthritis (RA).

Methods: This retrospective, non-interventional study used the OPAL dataset, derived from electronic medical records. Patients initiated UPA (N = 2624), other JAKis (baricitinib and tofacitinib [N = 925]), or TNFis (adalimumab, etanercept, certolizumab, golimumab, infliximab [N = 3540]) between May 2020 and March 2023.

Pre-Hospital ECPR cost analysis and cost effectiveness modelling study.

Background: The use of extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) is increasing. Prehospital ECPR (PH-ECPR) for out-of-hospital cardiac arrest (OHCA) may improve both equity of access and outcomes but its cost effectiveness has yet to be determined.

Methods: Cost analyses of PH-ECPR was performed utilizing current PH-ECPR trial, NSW Ambulance Cardiac Arrest Registry (CAR), geospatial modelling and in-hospital costings data.

Rescue therapy after failed thrombectomy in medium/distal vessel occlusions: A retrospective analysis of an international, multi-center registry.

Background: There are limited therapeutic options in cases of failed reperfusion (modified thrombolysis in cerebral infarction [mTICI] score < 2b) after stent-retriever and/or aspiration based endovascular treatment (EVT) for acute ischemic stroke. Despite the absence of data supporting its use, rescue therapy (balloon angioplasty and/or stent implantation) is often utilized in such cases. Studies are limited to large vessel occlusions, while the outcomes and complications after rescue therapy in medium/distal vessel occlusions (MDVOs) have not been reported.

Affinity maturation endows potent activity onto class 6 SARS-CoV-2 broadly neutralizing antibodies.

The emergence of SARS-CoV-2 variants of concern (VOCs) has greatly diminished the neutralizing activity of previously FDA-approved monoclonal antibodies (mAbs), including that of antibody cocktails and of first-generation broadly neutralizing antibodies such as S309 (Sotrovimab). In contrast, antibodies targeting cryptic conformational epitopes of the receptor binding domain (RBD) have demonstrated broad activity against emerging variants, but exert only moderate neutralizing activity, which has so far hindered clinical development. Here, we utilize in vitro display technology to identify and affinity-mature antibodies targeting the cryptic class 6 epitope, accessible only in the "up" conformation of the SARS-CoV-2 spike trimer.

Rethinking the pan scan in stable trauma: A comparison of whole-body computed tomography and selective imaging in clinically stable blunt force trauma.

Objective: To compare the frequency of clinically significant missed injuries in clinically stable trauma patients undergoing initial whole-body computed tomography (WBCT) versus selective imaging. Secondary objectives include comparisons of radiation exposure, incidental findings, ED length of stay (LOS), hospital LOS and mortality.

Methods: We performed a retrospective cohort study of trauma activations at a tertiary trauma centre in patients with normal vital signs from 1st January 2022 to 31st December 2022.

DREAM: an adaptive, randomised, placebo-controlled trial of duloxetine for reducing leg pain in people with chronic sciatica-trial protocol.

Introduction: Sciatica is a debilitating condition that often becomes chronic, and for which there are few effective treatment options. Treatments such as the anti-depressant duloxetine have shown promise, but the evidence is inconclusive. We are describing a high quality, definitive trial to investigate the efficacy, safety and cost-effectiveness of duloxetine in chronic sciatica.

Effectiveness of an online food shopping intervention to reduce salt purchases among individuals with hypertension - findings of the SaltSwitch Online Grocery Shopping (OGS) randomised trial.

Background: Online grocery shopping is a growing source of food purchases in many countries. We investigated the effect of nudging consumers towards purchases of lower sodium products using a web browser extension.

Methods: This trial was conducted among individuals with hypertension who shopped for their groceries online in Australia.

A comparison of the accuracy and feasibility of a low-cost mobile application versus higher-cost handheld 3D scanner for digital ear prosthetics.

Background: Facial prosthetics are an important means to rehabilitate patients with congenital or acquired facial defects. However, with a time-consuming manual workflow and workforce shortage, access to facial prosthetics is limited in Australia and worldwide, especially for rural and remote patients. Optical 3D scanning has been increasingly integrated in digitizing data.