Pancreatic ductal adenocarcinoma (PDAC) is characterized by increasing fibrosis, which can enhance tumor progression and spread. Here, we undertook an unbiased temporal assessment of the matrisome of the highly metastatic KPC (, , ) and poorly metastatic KPC (, , ) genetically engineered mouse models of pancreatic cancer using mass spectrometry proteomics. Our assessment at early-, mid-, and late-stage disease reveals an increased abundance of nidogen-2 (NID2) in the KPC model compared to KPC, with further validation showing that NID2 is primarily expressed by cancer-associated fibroblasts (CAFs).
View Article and Find Full Text PDFIntroduction: Neoadjuvant chemoradiation therapy (NCRT) for cT1b esophageal cancer is not recommended despite the risk of pathologic upstaging with increased depth of penetration. We aimed to (1) define the rate of and factors associated with pathologic upstaging, (2) describe current trends in treatments, and (3) compare overall survival (OS) with and without NCRT for surgically resected cT1b lesions.
Methods: We used the 2020 National Cancer Database to identify patients with cT1b N0 esophageal cancer with or without pathologic upstaging who underwent removal of their tumor.
Background: An on-site pharmacist (OSP) intervention was implemented which sought to improve medication management within residential aged care facilities (RACFs) in the Australian Capital Territory, Australia. The objectives of this mixed methods study were to evaluate the implementation fidelity of the OSP intervention and to determine the moderating factors which influenced delivery of this intervention.
Methods: This convergent parallel mixed methods study was underpinned by Hasson's conceptual framework for implementation fidelity.
Black patients have the highest overall incidence rate of early onset colorectal cancer, with many of these patients presenting with more aggressive disease at diagnosis, ultimately leading to decreased overall survival. We aimed to (1) evaluate how race and age affected overall survival in colorectal cancer patients, and (2) determine the different demographic and clinical covariables that may influence survival in younger individuals. The 2017 National Cancer Database (NCDB) was used to identify all patients that had colorectal cancer between 2004-2017.
View Article and Find Full Text PDFBackground: A new on-site pharmacist (OSP) intervention within residential aged care facilities (RACFs) is being investigated to help improve medication management. Interprofessional collaboration amongst prescribers, nursing staff and pharmacists is critical to improving RACF medication management.
Objective: To explore the extent of interprofessional collaboration and the nature of the working relationships between OSPs and prescribers, managers and nursing staff.
The gut microbiota shapes the response to immune checkpoint inhibitors (ICIs) in cancer, however dietary and geographic influences have not been well-studied in prospective trials. To address this, we prospectively profiled baseline gut (fecal) microbiota signatures and dietary patterns of 103 trial patients from Australia and the Netherlands treated with neoadjuvant ICIs for high risk resectable metastatic melanoma and performed an integrated analysis with data from 115 patients with melanoma treated with ICIs in the United States. We observed geographically distinct microbial signatures of response and immune-related adverse events (irAEs).
View Article and Find Full Text PDFBackground: The medication expertise of pharmacists is widely acknowledged and there is ongoing interest in their potential role to reduce medication-related harm amongst residents living in residential aged care facilities (RACFs). An increased understanding of how these interventions are evaluated could support adoption of these interventions in the real world.
Objective: To systematically explore the application of evaluation approaches, evaluation tools and aspects of implementation (implementation factors i.
While immune checkpoint inhibitors targeting the CTLA-4 and PD-1 receptors have significantly improved outcomes of many patients with metastatic melanoma, there remains a group of patients who demonstrate no benefit. In this study, we sought to characterise patients who do not respond to anti-PD-1-based therapies based on their clinical, genetic and immune profiles. Forty patients with metastatic melanoma who did not respond to anti-PD-1 +/- anti-CTLA-4 treatment were identified.
View Article and Find Full Text PDFBackground: Coronavirus disease 2019 (COVID-19) can cause serious complications such as multiorgan failure and death which are difficult to predict. We conducted this retrospective case-control observational study with the hypothesis that low serum albumin at presentation can predict serious outcomes in COVID-19 infection.
Methods: We included severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed, hospitalized patients from March to July 2020 in a tertiary care hospital in the USA.
Late-onset Pompe disease (LOPD) is an inherited autosomal recessive progressive metabolic myopathy that presents in the first year of life to adulthood. Clinical presentation is heterogeneous, differential diagnosis is challenging, and diagnostic delay is common. One challenge to differential diagnosis is the overlap of clinical features with those encountered in other forms of acquired/hereditary myopathy.
View Article and Find Full Text PDFBackground: The data on the COVID-19 patients who were discharged to self-quarantine is lacking.
Aim: The aim of the study was to investigate the percentage of COVID-19 positive patients that were hospitalized within a three-week period after discharge from ED to self-quarantine.
Methods: The patients who had confirmed SARS-CoV-2 on RT-PCR of the nasopharyngeal swab and were discharged from ED of a tertiary care hospital in the USA to self-quarantine from March 01- July 31, 2020, were included.
To address progressive respiratory muscle weakness in late-onset Pompe disease (LOPD), we developed a 12-week respiratory muscle training (RMT) program. In this exploratory, double-blind, randomized control trial, 22 adults with LOPD were randomized to RMT or sham-RMT. The primary outcome was maximum inspiratory pressure (MIP).
View Article and Find Full Text PDFImmune checkpoint blockade has greatly improved the clinical outcomes of many patients with metastatic melanoma, however, almost half do not respond. Whether the interspatial distribution of immune and tumor cells predicts response to anti-PD-1-based therapies and patient outcomes in any cancer, including melanoma, is currently unknown. Here, we examined the spatial distribution of immune and tumor cells via multiplex immunofluorescence.
View Article and Find Full Text PDFMetal-organic frameworks (MOFs) have an unprecedented ability to store gas molecules, however energy efficient regeneration remains challenging. Use of magnetic induction to aid this shows promise, but economical synthesis of the requisite composites is unresolved. Continuous flow chemistry has been reported as a rapid and reliable method of MOF synthesis, delivering step-change improvements in space time yields (STY).
View Article and Find Full Text PDFIntroduction:: Morbidity and mortality in adults with late-onset Pompe disease (LOPD) results primarily from persistent progressive respiratory muscle weakness despite treatment with enzyme replacement therapy (ERT). To address this need, we have developed a 12-week respiratory muscle training (RMT) program that provides calibrated, individualized, and progressive pressure-threshold resistance against inspiration and expiration. Our previous results suggest that our RMT regimen is safe, well-tolerated, and results in large increases in respiratory muscle strength.
View Article and Find Full Text PDFBackground: There is a gap in knowledge about the kind and quality of care experienced by hospital patients at the end of their lives.
Aims: To document and compare the patterns in end-of-life care for patients dying across a range of different medical units in an acute care hospital.
Methods: A retrospective observational study of consecutive adult inpatient deaths between 1 July 2010 and 30 June 2014 in four different medical units of an Australian tertiary referral hospital was performed.
Cancer immunotherapies provide survival benefits in responding patients, but many patients fail to respond. Identifying the biology of treatment response and resistance are a priority to optimize drug selection and improve patient outcomes. We performed transcriptomic and immune profiling on 158 tumor biopsies from melanoma patients treated with anti-PD-1 monotherapy (n = 63) or combined anti-PD-1 and anti-CTLA-4 (n = 57).
View Article and Find Full Text PDF: Anti-PD-1 therapy has revolutionized the treatment and improved the survival of stage IV melanoma patients. However, almost half of the patients fail to respond due to immune evasive mechanism. A known mechanism is the downregulation of major histocompatibility complex (MHC) class I expression, which prevents T cell recognition of the tumor.
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