A cost utility analysis for the management of acute exacerbations of chronic rhinosinusitis.

Background: The management of acute exacerbations of chronic rhinosinusitis (AECRS) is understudied and the most cost-effective management of AECRS has not been previously investigated. The aim of this study is to determine the most cost-effective strategy for the initial management of AECRS.

Methods: The study design consisted of a decision-tree economic model comparing three different initial strategies for managing a patient perceived AECRS: observation, upfront rescue medications, or clinic visit with diagnostic nasal endoscopy (DNE).

Patient-reported disease control versus overall symptom severity as global metrics of chronic rhinosinusitis disease status.

Background: Overall symptom severity (OSS) and patient-reported chronic rhinosinusitis (CRS) control are global measures of CRS identified as consensus, essential criteria for CRS disease control assessment. We sought to determine the functional relationship between these two metrics.

Methods: Using an international multicenter mixed-methods design, 260 CRS patients were recruited.

Design, Construction, and Test of Compact, Distributed-Charge, X-Band Accelerator Systems that Enable Image-Guided, VHEE FLASH Radiotherapy.

The design and optimization of laser-Compton x-ray systems based on compact distributed charge accelerator structures can enable micron-scale imaging of disease and the concomitant production of beams of Very High Energy Electrons (VHEEs) capable of producing FLASH-relevant dose rates. The physics of laser-Compton x-ray scattering ensures that the scattered x-rays follow exactly the trajectory of the incident electrons, thus providing a route to image-guided, VHEE FLASH radiotherapy. The keys to a compact architecture capable of producing both laser-Compton x-rays and VHEEs are the use of X-band RF accelerator structures which have been demonstrated to operate with over 100 MeV/m acceleration gradients.

Pleomorphic Hyalinizing Angiectatic Tumor of the Larynx.

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare, benign soft tissue tumor with uncertain pathogenesis and lineage most commonly found in the lower and upper extremities. No reports exist of this tumor metastasizing, though local recurrence is common. To date, only approximately 100 cases have been reported.

Association of Circulating Plasma Secreted Frizzled-Related Protein 5 (Sfrp5) Levels with Cardiac Function.

Secreted frizzled-related protein 5 (SFRP5) is a novel anti-inflammatory adipokine that may play a role in cardiovascular development and disease. However, there is yet to be a comprehensive investigation into whether circulating SFRP5 can be a biomarker for cardiac function. Plasma SFRP5 levels were measured via ELISA in 262 patients admitted to a cardiology unit.

Comparing the resource implications of old and new colorectal adenoma surveillance guidelines in Australia.

Background: The latest update to the Australian adenoma surveillance guideline in 2018 introduced a novel risk stratification system with updated surveillance recommendations. The resource implications of adopting this new system are unclear.

Aims: To quanitfy the resource demands of adopting new over old adenoma surveillance guidelines.

Potentially avoidable mortality after endoscopic retrograde cholangiopancreatography in Australia: an 8-year qualitative analysis.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is a commonly performed procedure worldwide. The aim of this study was to examine cases of mortality after ERCP to identify clinical incidents that are potentially preventable, to improve patient safety.

Methods: The Australian and New Zealand Audit of Surgical Mortality provides an independent and externally peer-reviewed audit of surgical mortality pertaining to potentially avoidable issues.

Quality of colonoscopy performed by medical or surgical specialists and trainees in five Australian hospitals.

Background: Ensuring colonoscopy procedure quality is vital to the success of screening and surveillance programmes for bowel cancer in Australia. However, the data on the performance of quality metrics, through adequate adenoma detection, bowel preparation, and procedure completion rates, in the Australian public sector is limited. Understanding these can inform quality improvement to further strengthen our capacity for prevention and early detection of colorectal cancer.

Intraocular pressure improvement in patients receiving teprotumumab for the treatment of thyroid eye disease: a case series.

Background: Teprotumumab is a novel treatment that reduces inflammation and symptoms caused by thyroid eye disease. There are limited data on teprotumumab's effect on intraocular pressure.

Case Presentation: We report nine patients diagnosed with thyroid eye disease whose intraocular pressure decreased during teprotumumab treatment for 8 weeks: patient 1, a 67-year-old Hispanic woman; patient 2, an 86-year-old African-American man; patient 3, a 71-year-old Caucasian woman; patient 4, a 72-year-old Hispanic woman; patient 5, a 65-year-old Caucasian woman; patient 6, a 54-year-old Caucasian man; patient 7, a 54-year-old Asian man; patient 8, a 31-year-old Asian woman; patient 9, a 60-year-old Caucasian woman.

The impact of sleep events on weight gain following early adenotonsillectomy compared to supportive care for pediatric OSA.

Objectives: Children with obstructive sleep apnea (OSA) who undergo adenotonsillectomy (AT) often experience post-operative weight gain, although the mechanism remains unclear. Our aim is to understand how changes in sleep events impact changes in weight in children with OSA following adenotonsillectomy compared to watchful waiting with supportive care.

Methods: We performed a secondary analysis of the Childhood adenotonsillectomy trial (CHAT) dataset in which children with OSA were randomized to undergo early adenotonsillectomy (eAT) or watchful waiting with supportive care (WWSC).

An Engineered IL15 Cytokine Mutein Fused to an Anti-PD1 Improves Intratumoral T-cell Function and Antitumor Immunity.

The use of cytokines for immunotherapy shows clinical efficacy but is frequently accompanied by severe adverse events caused by excessive and systemic immune activation. Here, we set out to address these challenges by engineering a fusion protein of a single, potency-reduced, IL15 mutein and a PD1-specific antibody (anti-PD1-IL15m). This immunocytokine was designed to deliver PD1-mediated, avidity-driven IL2/15 receptor stimulation to PD1 tumor-infiltrating lymphocytes (TIL) while minimally affecting circulating peripheral natural killer (NK) cells and T cells.

Crystal structure of dopamine D1 receptor in complex with G protein and a non-catechol agonist.

Dopamine D1 receptor (D1R) is an important drug target implicated in many psychiatric and neurological disorders. Selective agonism of D1R are sought to be the therapeutic strategy for these disorders. Most selective D1R agonists share a dopamine-like catechol moiety in their molecular structure, and their therapeutic potential is therefore limited by poor pharmacological properties in vivo.

Rhopressa-induced corneal edema: a case report.

Background: Rhopressa (netarsudil) has recently been added to the arsenal of treatment for open-angle glaucoma. It is an effective norepinephrine transporter and Rho-associated protein kinase (ROCK) inhibitor used to decrease intraocular pressure (IOP), with the most common side effect being conjunctival hyperemia.

Case Presentation: We report a unique case of Rhopressa-induced corneal edema in a 79-year-old African-American woman, which resolved after discontinuation.

One size does not fit all: navigating the multi-dimensional space to optimize T-cell engaging protein therapeutics.

T-cell engaging biologics is a class of novel and promising immune-oncology compounds that leverage the immune system to eradicate cancer. Here, we compared and contrasted a bispecific diabody-Fc format, which displays a relatively short antigen-binding arm distance, with our bispecific IgG platform. By generating diverse panels of antigen-expressing cells where B cell maturation antigen is either tethered to the cell membrane or located to the juxtamembrane region and masked by elongated structural spacer units, we presented a systematic approach to investigate the role of antigen epitope location and molecular formats in immunological synapse formation and cytotoxicity.

Inappropriate noise detection in Tendril family pacing leads.

Introduction: Noise oversensing encountered in patients with Abbott Tendril leads in our hospital triggered an internal investigation.

Methods: We retrospectively analyzed patients with a Tendril lead model 1688, 1788, 1888, and 2088. Most leads were connected to Abbott generators.

Ligand-Blocking and Membrane-Proximal Domain Targeting Anti-OX40 Antibodies Mediate Potent T Cell-Stimulatory and Anti-Tumor Activity.

Agonistic antibodies targeting the tumor necrosis factor (TNF) superfamily of co-stimulatory receptors (TNFRSF) are progressing through various stages of clinical development for cancer treatment, but the desired and defining features of these agents for optimal biological activity remain controversial. One idea, based on recent studies with CD40, is that non-ligand-blocking antibodies targeting membrane-distal cysteine-rich domain 1 (CRD1) have superior agonistic activities compared with ligand-blocking antibodies targeting more membrane-proximal CRDs. Here, we determined the binding and functional characteristics of a panel of antibodies targeting CRDs 1-4 of OX40 (also known as TNFRSF4 or CD134).

Outcomes at non-trauma centres within a trauma referral network: A five-year retrospective cohort study from Australia.

Objective: Describe major trauma activity and mortality within non-trauma centres within a single trauma referral network in New South Wales, Australia over a five-year period.

Design: Multi-centre retrospective cohort study.

Methods: This was a retrospective cohort study of trauma patients presenting to non-trauma centres within a metropolitan major trauma referral network between January 2011 and June 2016.

Author Correction: Structural insights into the activation of metabotropic glutamate receptors.

The surname of author Toon Laeremans was misspelled 'Laermans'. This error has been corrected online.

Structural insights into the activation of metabotropic glutamate receptors.

Metabotropic glutamate receptors are family C G-protein-coupled receptors. They form obligate dimers and possess extracellular ligand-binding Venus flytrap domains, which are linked by cysteine-rich domains to their 7-transmembrane domains. Spectroscopic studies show that signalling is a dynamic process, in which large-scale conformational changes underlie the transmission of signals from the extracellular Venus flytraps to the G protein-coupling domains-the 7-transmembrane domains-in the membrane.

Targeted Elimination of Immunodominant B Cells Drives the Germinal Center Reaction toward Subdominant Epitopes.

Rapidly evolving pathogens such as HIV or influenza can quickly mutate their antigenic profiles, reducing the efficacy of conventional vaccines. Despite this challenge, functionally required epitopes are highly conserved among heterologous viral strains and represent a key vulnerability that could be targeted during vaccine development. As the antigenicity of these conserved epitopes is frequently subdominant, there is a critical need for innovative vaccination strategies designed to target these neutralizing epitopes.

Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein.

Glucagon-like peptide 1 (GLP-1) is a hormone with essential roles in regulating insulin secretion, carbohydrate metabolism and appetite. GLP-1 effects are mediated through binding to the GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor (GPCR) that signals primarily through the stimulatory G protein G. Class B GPCRs are important therapeutic targets; however, our understanding of their mechanism of action is limited by the lack of structural information on activated and full-length receptors.

Management of functional Sprint Fidelis leads at cardiac resynchronization therapy-defibrillator generator replacement: a novel option for preventing inappropriate shocks from lead failure in fragile patients with high risk of sudden death.

Aims: In patients with a functional Sprint Fidelis lead at generator replacement, the manufacturer recommended to either continue to use the existing lead or replace it with a new lead. For those patients who continue to use a functional Fidelis lead, the risk of inappropriate shocks remains present if the lead fails in the future. We evaluated the feasibility of an alternative approach at the time of cardiac resynchronization therapy-defibrillator (CRT-D) generator replacement in patients with a functional bipolar left ventricular (LV) lead for prevention of inappropriate shocks from future Fidelis lead failure.