Real-world impact of pembrolizumab availability for deficient mismatch repair metastatic colorectal cancer.

Background: Immunotherapy has emerged as a standard treatment for deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC). Pembrolizumab became widely available as a first-line (1L) option in Australia following the Pharmaceutical Benefits Scheme (PBS) listing in August 2021. The uptake of new treatment options can be lengthy.

Initial Assessment of Resectability of Colorectal Cancer Liver Metastases Versus Clinical Outcome.

Background: Surgery improves long-term survival for resectable, liver-only metastatic colorectal cancer (mCRC). With no consensus definition of "resectable" disease, decisions regarding resectability are reliant on the expertise and judgement of the treating clinician working in consultation with a multidisciplinary team (MDT). This study examines the clinical outcome versus initial assessment of resectability in an Australian population with mCRC.

Medicine Access Programmes: what do patients think - a patient-reported outcome study on ribociclib in metastatic breast cancer in Australia.

This study evaluated patient-reported outcomes (PROs) of Medicine Access Programmes (MAPs) for Australian metastatic breast cancer patients on ribociclib. Limited patient awareness of MAP enrolment was identified, emphasising the need for improved education and consent processes. Most patients expressed gratitude for accessing non-funded medications and perceived enhanced medication adherence as a key benefit.

Mobile chat messaging for preventing relapse among people who recently quit smoking: Study protocol for a randomized controlled trial.

Objective: Most smokers who achieve short-term abstinence relapse even when aided by evidence-based cessation treatment. Mobile health presents a promising but largely untested avenue for providing adjunct behavioral support for relapse prevention. This paper presents the rationale and design of a randomized controlled trial aimed at evaluating the effectiveness of personalized mobile chat messaging support for relapse prevention among people who recently quit smoking.

Comprehensive Stress Stability Studies Reveal the Prominent Stability of the Liquid-Formulated Biotherapeutic Asymmetric Monovalent Bispecific IgG1 Monoclonal Antibody Format.

The developed asymmetric monovalent bispecific IgG1 or Duet monoclonal antibody (Duet mAb) has two distinct fragment antigen-binding region (Fab) subunits that target two different epitope specificities sequentially or simultaneously. The design features include unique engineered disulfide bridges, knob-into-hole mutations, and kappa and lambda chains to produce Duet mAbs. These make it structurally and functionally complex, so one expects challenging developability linked to instability, degradation of products and pathways, and limited reports available.

Immune cell expression patterns of CD39/CD73 ectonucleotidases in rodent models of cardiac arrest and resuscitation.

Background: Cardiac arrest (CA) is a significant public health concern. There is the high imminent mortality and survival in those who are resuscitated is substantively compromised by the post-CA syndrome (PCAS), characterized by multiorgan ischemia-reperfusion injury (IRI). The inflammatory response in PCAS is complex and involves various immune cell types, including lymphocytes and myeloid cells that have been shown to exacerbate organ IRI, such as myocardial infarction.

Identification and quantification of chain-pairing variants or mispaired species of asymmetric monovalent bispecific IgG1 monoclonal antibody format using reverse-phase polyphenyl chromatography coupled electrospray ionization mass spectrometry.

Developing a knob-into-hole asymmetric bispecific IgG1 monoclonal antibody (mAb) poses manufacturing challenges due to the expression of chain pairing variants, also called mispaired species, in the desired product. The incorrect pairing of light and heavy chains could result in heterogeneous mispaired species of homodimers, heterodimers, light chain swapping, and low molecular weight species (LMWS). Standard chromatography, capillary electrophoretic, or spectroscopic methods poorly resolve these from the main variants.

Pulmonary embolism response teams. A description of the first 36-month Australian experience.

Background: High/intermediate-risk pulmonary embolism (PE) confers increased risk of cardiovascular morbidity and mortality. International guidelines recommend the formation of a PE response team (PERT) for PE management because of the complexity of risk stratification and emerging treatment options. However, there are currently no available Australian data regarding outcomes of PE managed through a PERT.

Low respiratory quotient correlates with high mortality in patients undergoing mechanical ventilation.

Objective: Oxygen consumption (VO), carbon dioxide generation (VCO), and respiratory quotient (RQ), which is the ratio of VO to VCO, are critical indicators of human metabolism. To seek a link between the patient's metabolism and pathophysiology of critical illness, we investigated the correlation of these values with mortality in critical care patients.

Methods: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital.

Understanding the Role of Yes-Associated Protein (YAP) Signaling in the Transformation of Lens Epithelial Cells (EMT) and Fibrosis.

Fibrotic cataracts, posterior capsular opacification (PCO), and anterior subcapsular cataracts (ASC) are mainly attributed to the transforming growth factor-β (TGFβ)-induced epithelial-to-mesenchymal transition (EMT) of lens epithelial cells (LECs). Previous investigations from our laboratory have shown the novel role of non-canonical TGFβ signaling in the progression of EMT in LECs. In this study, we have identified YAP as a critical signaling molecule involved in lens fibrosis.

Insufficient Oxygen Supplementation During Cardiopulmonary Resuscitation Leads to Unfavorable Biological Response While Hyperoxygenation Contributes to Metabolic Compensation.

Sudden cardiac arrest (CA) is the third leading cause of death. Immediate reoxygenation with high concentrations of supplemental oxygen (O) during cardiopulmonary resuscitation (CPR) is recommended according to the current guidelines for adult CA. However, a point in controversy exists because of the known harm of prolonged exposure to 100% O.

Continuous and repeat metabolic measurements compared between post-cardiothoracic surgery and critical care patients.

Objective: Using a system, which accuracy is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (VO), carbon dioxide generation (VCO), and respiratory quotient (RQ), we aimed to continuously measure these metabolic indicators and compare the values between post-cardiothoracic surgery and critical care patients.

Methods: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older patients who underwent mechanical ventilation were enrolled.

Resident Engagement With a Web- and App-based Journal Club Curriculum Utilizing Email and Text Notifications.

Background: High learner engagement is important for the success of asynchronous and online learning for graduate medical education. Medical trainees have recently reported using medical mobile apps. App-based interactions may provide more participation than email-based interactions.

Pediatric Intensive Care Unit Early Mobility Program: Impact on Patient Functional Status.

Introduction: Patients admitted to the pediatric Intensive Care Unit (PICU) are frequently sedated, restrained, and placed on bed rest. These practices have known negative impacts including prolonged hospital stay and diminished functional status after discharge. The authors' objective was to investigate the impact of a PICU early mobility protocol on the frequency of orders for physical, occupational, and speech therapy (PT, OT, ST) and improvement in patient functional status.

The role of pyruvate-induced enhancement of oxygen metabolism in extracellular purinergic signaling in the post-cardiac arrest rat model.

Purine nucleotide adenosine triphosphate (ATP) is a source of intracellular energy maintained by mitochondrial oxidative phosphorylation. However, when released from ischemic cells into the extracellular space, they act as death-signaling molecules (eATP). Despite there being potential benefit in using pyruvate to enhance mitochondria by inducing a highly oxidative metabolic state, its association with eATP levels is still poorly understood.

How Institution of the Sup-ER Protocol in a Clinic Changed Procedure Patterns in Upper Brachial Plexus (Erb's Type) Birth Injuries.

Background: For children with upper brachial plexus birth injury (BPBI; C5, C6, ±C7 roots), most clinics first recommend nonsurgical treatment followed by primary and/or secondary surgical interventions in selected patients. Since 2008, we have used an infant shoulder repositioning protocol (supination-external rotation [Sup-ER]) designed to prevent shoulder internal rotation contracture and its potential effects on the shoulder joint. This study characterizes our clinic's current choice, number, and timing of primary and secondary procedural interventions (including Botox) and compares Sup-ER protocol patients with those of our historical controls.

Insufficient oxygen inhalation during cardiopulmonary resuscitation induces early changes in hemodynamics followed by late and unfavorable systemic responses in post-cardiac arrest rats.

Cardiac arrest (CA) and concomitant post-CA syndrome lead to a lethal condition characterized by systemic ischemia-reperfusion injury. Oxygen (O ) supply during cardiopulmonary resuscitation (CPR) is the key to success in resuscitation, but sustained hyperoxia can produce toxic effects post CA. However, only few studies have investigated the optimal duration and dosage of O administration.

Novel Three-Dimensional Printed Human Heart Models and Ultrasound Omniplane Simulator for Transesophageal Echocardiography Training.

Simulation-based training plays an essential role in transesophageal echocardiography (TEE) education. Using 3-dimensional printing technology, the authors invented a novel TEE teaching system consisting of a series of heart models that can be segmented according to actual TEE views, and an ultrasound omniplane simulator to demonstrate how ultrasound beams intersect the heart at different angles and generate images. This novel teaching system is able to provide a more direct way to visualize the mechanics of obtaining TEE images than traditional online or mannequin-based simulators.

Bio-physiological susceptibility of the brain, heart, and lungs to systemic ischemia reperfusion and hyperoxia-induced injury in post-cardiac arrest rats.

Cardiac arrest (CA) patients suffer from systemic ischemia-reperfusion (IR) injury leading to multiple organ failure; however, few studies have focused on tissue-specific pathophysiological responses to IR-induced oxidative stress. Herein, we investigated biological and physiological parameters of the brain and heart, and we particularly focused on the lung dysfunction that has not been well studied to date. We aimed to understand tissue-specific susceptibility to oxidative stress and tested how oxygen concentrations in the post-resuscitation setting would affect outcomes.

Fate and recovery of nitrogen applied as slow release brown coal-urea in field microcosms: N tracer study.

The over-use of synthetic nitrogen (N) fertilisers for crop production can cause environmental pollution through leaching and gaseous losses, resulting in low N use efficiency (NUE). Previous work has shown that brown coal (BC) combined with urea can slow down the fertiliser-N release to better synchronise soil N supply with crop N demand. The study aimed to evaluate the impact of granulated BC-urea (BCU) applied to sweet corn on NUE, fate and recovery of fertiliser-N using an N tracer technique.

Motion Analysis: An Objective Assessment of Special Operations Forces and Tactical Medics Performing Point-of-Care Ultrasound.

Background: Point-of-care ultrasound (POCUS) is commonly employed to image the heart, lungs, and abdomen. Rapid ultrasound for shock and hypotension (RUSH) exams are a critical component of POCUS employed in austere environments by Special Operations Forces (SOF) and tactical medics for triage and diagnosis. Despite its utility, training for POCUS remains largely unstandardized with respect to feedback and markers of proficiency.

"Nothing to lose and the possibility of gaining": a qualitative study on the feasibility and acceptability of registry-based randomised controlled trials among cancer patients and clinicians.

Background: Randomised controlled trials (RCTs) are considered the "gold standard" for evaluating the effectiveness of interventions in clinical research. However, conventional RCTs are typically complex, expensive, and have narrow eligibility criteria, which limits generalisability. Registry-based randomised controlled trials (RRCTs) are an alternative approach that integrates the internal validity of an RCT with the external validity of a clinical registry by recruiting real-world patients and leveraging an existing registry platform for data collection.

Systematic analytical workflow for characterisation and identification of partially reduced species in monoclonal antibody manufacturing.

Fragmentation is a major degradation pathway ubiquitous to all therapeutic monoclonal antibody (mAb) and therefore, monitored throughout the manufacturing process. Here, we describe a three-step approach to 1) detect, 2) confirm and 3) characterize partially reduced fragment species in an immunoglobulin G1 (IgG1) mAb with prolonged hold time of harvested cell culture fluid (HCCF). Microchip capillary electrophoresis (MCE) and high-performance size exclusion chromatography (HPSEC) were used as fast and efficient screening methods to detect fragmentation.