TEP in the ER: After Hours Tracheoesophageal Prosthesis Management for the Otolaryngologist.

Background: Tracheoesophageal voice puncture and prosthesis (TEP) is a common method of voice restoration following total laryngectomy. A variety of complications, both minor and major, can be associated with the TEP and require timely intervention/management. Some of those complications include premature leakage, periprosthetic leakage, granulation tissue growth, TEP dislodgement, or embedding of the TEP.

HER2 overexpression in urothelial carcinoma with GATA3 and PPARG copy number gains.

HER2, encoded by the ERBB2 gene, is an important druggable driver of human cancer gaining increasing importance as a therapeutic target in urothelial carcinoma (UC). The genomic underpinnings of HER2 overexpression in ERBB2 nonamplified UC are poorly defined. To address this knowledge gap, we investigated 172 UC tumors from patients treated at the University of California San Francisco, using immunohistochemistry and next-generation sequencing.

Putative Cancer Stem Cell Markers are Frequently Expressed by Melanoma Cells and but are also Present in Benign Differentiated Cells.

Background: Currently, there remains an incomplete view of cancer stem cells (CSCs) in solid tumours.

Methods: We studied a panel of putative CSC surface markers (ALDH1A1, ABCG2, CD44v7/8, CD44v10, CD133, CD271, and Nestin) in 40 established melanoma cell lines and four early-passage melanoma strains by flow cytometry. We additionally examined 40 formalin-fixed paraffin-embedded melanoma tissues using immunofluorescence microscopy.

Somatic alterations of and associated with response to enfortumab vedotin in patients with advanced urothelial cancer.

Background: Enfortumab vedotin (EV) is an antibody-drug conjugate approved for patients with treatment-refractory advanced urothelial carcinoma (aUC), however data on biomarkers of response is lacking.

Methods: We retrospectively identified all aUC patients at our institution who received EV monotherapy and had next-generation sequencing (NGS) data available. Patients were considered responders if they had a complete response or partial response on restaging scans during treatment.

Asthma Management in Children.

Asthma is a common, complex heterogeneous disease often beginning in early life and is characterized by reversible airflow obstruction. The phenotypic differences that exist in children with asthma may impact underlying comorbid conditions and pharmacologic treatment choices. Prenatal factors for increased risk of asthma could include maternal diet and the maternal microbiome.

The epidemiology of out-of-hospital cardiac arrest in Australia and New Zealand: A binational report from the Australasian Resuscitation Outcomes Consortium (Aus-ROC).

Introduction: The Australasian Resuscitation Outcomes Consortium (Aus-ROC) out-of-hospital cardiac arrest (OHCA) Epistry (Epidemiological Registry) now covers 100% of Australia and New Zealand (NZ). This study reports and compares the Utstein demographics, arrest characteristics and outcomes of OHCA patients across our region.

Methods: We included all OHCA cases throughout 2019 as submitted to the Epistry by the eight Australian and two NZ emergency medical services (EMS).

Fluency and confidence predict paramedic diagnostic intuition: An experimental study of applied dual-process theory.

Introduction: We report an experiment using Australian paramedics (n = 64) and Australian paramedicine undergraduates (n = 44), on the processes underlying the formation of an intuitive diagnostic impression, based on limited dispatch information. Previous research has signalled roles for objective likelihood of the disease, subjective typicality of the disease, and the ease with which the diagnosis comes to mind (answer fluency) as important in impression formation.

Method: Participants completed four brief written clinical vignettes under time pressure and with a concurrent navigation task to simulate conditions faced by paramedics prior to meeting a patient.

Lipidome profiling with Raman microspectroscopy identifies macrophage response to surface topographies of implant materials.

Biomaterial characteristics such as surface topographies have been shown to modulate macrophage phenotypes. The standard methodologies to measure macrophage response to biomaterials are marker-based and invasive. Raman microspectroscopy (RM) is a marker-independent, noninvasive technology that allows the analysis of living cells without the need for staining or processing.

Altered Proinflammatory Responses to Polyelectrolyte Multilayer Coatings Are Associated with Differences in Protein Adsorption and Wettability.

A full understanding of the relationship between surface properties, protein adsorption, and immune responses is lacking but is of great interest for the design of biomaterials with desired biological profiles. In this study, polyelectrolyte multilayer (PEM) coatings with gradient changes in surface wettability were developed to shed light on how this impacts protein adsorption and immune response in the context of material biocompatibility. The analysis of immune responses by peripheral blood mononuclear cells to PEM coatings revealed an increased expression of proinflammatory cytokines tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1β, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6 and the surface marker CD86 in response to the most hydrophobic coating, whereas the most hydrophilic coating resulted in a comparatively mild immune response.

The Impact of Biomaterial Cell Contact on the Immunopeptidome.

Biomaterials play an increasing role in clinical applications and regenerative medicine. A perfectly designed biomaterial should restore the function of damaged tissue without triggering an undesirable immune response, initiate self-regeneration of the surrounding tissue and gradually degrade after implantation. The immune system is well recognized to play a major role in influencing the biocompatibility of implanted medical devices.

Diastereoselective Synthesis of P-Stereogenic Secondary Phosphine Oxides (SPOs) Bearing a Chiral Substituent by Ring Opening of (+)-Limonene Oxide with Primary Phosphido Nucleophiles.

Kinetic separation of the commercially available /-(+)-limonene oxide mixture by ring opening with primary phosphido nucleophiles LiPHR (R = ferrocenyl, Ph, Cy, -Bu, Mes* (Mes* = 2,4,6-(-Bu)CH)), followed by treatment with aqueous NHCl and HO, gave unreacted -(+)-limonene oxide and diastereoenriched mixtures of the secondary phosphine oxides (SPOs) PHR(-(+)-Lim-OH)(O), which could be separated by chromatography and/or recrystallization. This one-pot synthesis uses a cheap chiral material and commercially available primary phosphines to control the configuration of the new P-stereogenic SPOs, which are potentially useful as ligands for metal complexes in asymmetric catalysis.

Systematic Investigation of Polyurethane Biomaterial Surface Roughness on Human Immune Responses .

It has been widely shown that biomaterial surface topography can modulate host immune response, but a fundamental understanding of how different topographies contribute to pro-inflammatory or anti-inflammatory responses is still lacking. To investigate the impact of surface topography on immune response, we undertook a systematic approach by analyzing immune response to eight grades of medical grade polyurethane of increasing surface roughness in three models of the human immune system. Polyurethane specimens were produced with defined roughness values by injection molding according to the VDI 3400 industrial standard.

The National Ambulance Surveillance System: A novel method for monitoring acute alcohol, illicit and pharmaceutical drug related-harms using coded Australian ambulance clinical records.

Although harmful consumption of alcohol and other drugs (both illicit and pharmaceutical) significantly contribute to global burden of disease, not all harms are captured within existing morbidity data sources. Indeed, harms occurring in the community may be missed or under-reported. This paper describes the National Ambulance Surveillance System, a unique Australian system for monitoring and mapping acute harms related to alcohol and other drug consumption.

Frequency of Immune Cell Subtypes in Peripheral Blood Correlates With Outcome for Patients With Metastatic Breast Cancer Treated With High-Dose Chemotherapy.

Background: The frequency of circulating leukocytes has been shown to be a prognostic factor in patients being treated for different types of cancer. In breast cancer, tumor-infiltrating leukocytes may predict patient outcome, but few studies have investigated such associations for circulating leukocytes.

Patients And Methods: Multiparametric flow cytometry was used to examine the immunophenotypes of circulating peripheral blood mononuclear cells for 88 patients with metastatic breast cancer, which was then correlated to breast cancer-specific survival.

Management/Comorbidities of School-Aged Children with Asthma.

Asthma is a complex heterogeneous disease characterized by reversible airflow obstruction. After appropriate diagnosis, the management in school-aged children centers on 3 broad domains: pharmacologic treatment, treatment of underlying comorbidities, and education of the patient and caregivers. It is important to understand that the phenotypic differences that exist in the school-aged child with asthma may impact underlying comorbid conditions as well as pharmacologic treatment choices.

Expansion and Determination of Antigen-Reactive T Cells by Flow Cytometry.

The detection of antigen-reactive T cells has shown great utility for patient clinical monitoring. However, many of the methods commonly used to detect these cells face major limitations, like the predetermination of the given HLA type. The herein described protocol provides a means of overcoming many of the obstacles associated with the use of multimers and other common approaches in this field.

Low levels of intra-tumoural T cells in breast cancer identify clinically frail patients with shorter disease-specific survival.

Objectives: The global health status of older patients with cancer influences their clinical course, but little is known regarding the influence of the immune system on the global health of older patients with cancer. The goal of this study was to assess the relationships between patient fitness/frailty status and survival, and the local tumour immune environment of older patients with breast cancer.

Materials And Methods: In a cohort of 58 older patients with breast cancer (over 70 years of age), fluorescence microscopy was used to investigate whether levels of intra-tumoural T cells (CD3+) and granulocytic cells (CD15+) could predict clinical outcome, and/or whether they correlated with patient physical and mental performance as evaluated by comprehensive geriatric assessment.

Inhibiting HSP90 prevents the induction of myeloid-derived suppressor cells by melanoma cells.

Metastatic melanoma is the most dangerous form of skin cancer, with an ever-increasing incidence worldwide. Despite encouraging results with immunotherapeutic approaches, long-term survival is still poor. This is likely partly due to tumour-induced immune suppression mediated by myeloid-derived suppressor cells (MDSCs), which were shown to be associated with response to therapy and survival.

CD14+ HLA-DR-/low MDSCs are elevated in the periphery of early-stage breast cancer patients and suppress autologous T cell proliferation.

Purpose: Despite the recent expansion in the use of immunotherapy for many cancer types, it is still not a standard treatment for breast cancer. Identifying differences in the immune systems of breast cancer patients compared to healthy women might provide insight into potential targets for immunotherapy and thus may assist its clinical implementation.

Methods: Multi-colour flow cytometry was used to investigate myeloid and lymphoid populations in the peripheral blood of breast cancer patients (n = 40) and in the blood of healthy age-matched women (n = 25).

Immune profiles of elderly breast cancer patients are altered by chemotherapy and relate to clinical frailty.

Background: Effective therapeutic management of elderly patients with cancer, on an individual basis, remains a clinical challenge. Here, we identify novel biomarkers to assess elderly patients (≥70 years of age) with breast cancer undergoing treatment with or without chemotherapy.

Methods: We performed comprehensive geriatric assessment and measured markers sensitive to alteration in ageing, including leukocyte telomere length, CMV serostatus, levels of circulating growth factors and cytokines, and immune profiling of T cell and myeloid populations in blood before and at 3 months and 12 months after initiation of therapy, using flow cytometry.

Peripheral T cell responses to tumour antigens are associated with molecular, immunogenetic and cellular features of breast cancer patients.

Purpose: Breast cancer is a leading cause of cancer deaths in women, but despite steady improvements in therapies, treatment is still suboptimal. Immunotherapy holds promise as a more effective therapy for breast cancer; supporting this, our prior study showed that patients possessing HER2-reactive CD8+ T cells in blood experience survival superior to patients without these cells. Here, we define a composite set of biomarkers that identify patients with T cell responses to tumour antigens.