BACKGROUND AND PURPOSE: Cardiovascular risk factors significantly increase the risk of developing Alzheimer disease. A possible mechanism may be via ischemic infarction-driving amyloid deposition. We conducted a study to determine the presence of β-amyloid in infarct, peri-infarct, and hemispheric areas after stroke. We hypothesized that an infarct would trigger β-amyloid deposition, with deposition over time. METHODS: Patients were recruited within 40 days of acute ischemic stroke and imaged with computed tomographic or magnetic resonance imaging and Pittsburgh compound B (11C-PiB) positron emission tomographic scans. Follow-up positron emission tomographic scanning was performed in a subgroup ≤18 months after the stroke event. Standardized uptake value ratios for regions of interest were analyzed after coregistration. RESULTS: Forty-seven patients were imaged with (11)C-PiB positron emission tomography. There was an increase in (11)C-PiB accumulation in the stroke area compared with a reference region in the contralesional hemisphere, which was not statistically significant (median difference in standardized uptake value ratio, 0.07 [95% confidence interval, -0.06 to 0.123]; P=0.452). There was no significant increase in the accumulation of (11)C-PiB in the peri-infarct region or in the ipsilesional hemisphere (median difference in standardized uptake value ratio, 0.04 [95% confidence interval, -0.02 to 0.10]; P=0.095). We repeated (11)C-PiB positron emission tomography in 21 patients and found a significant reduction in accumulation of (11)C-PiB between regions of interest (median difference in standardized uptake value ratio, -0.08 [95% confidence interval, -0.23 to -0.03]; P=0.04). CONCLUSIONS: There was no significant increase in (11)C-PiB accumulation in or around the infarct. There was no increase in ipsilesional hemispheric (11)C-PiB accumulation over time. We found no evidence that infarction leads to sustained or increased β-amyloid deposition ≤18 months after stroke.

MAIT cells are MR1-restricted T cells that are well-known for their anti-microbial properties, but they have recently been associated with different forms of cancer. Several studies have reported activated MAIT cells within the microenvironment of colorectal tumors, but there is conjecture about the nature of their response and whether they are contributing to anti-tumor immunity, or to the progression of the disease. We have reviewed the current state of knowledge about the role of MAIT cells in colorectal cancer, including their likely influence when activated and potential sources of stimulation in the tumor microenvironment. The prospects for MAIT cells being used in clinical settings as biomarkers or as targets of new immunotherapies designed to harness their function are discussed.

BACKGROUND & AIMS: Hirschsprung disease (HSCR) is caused by failure of cells derived from the neural crest (NC) to colonize the distal bowel in early embryogenesis, resulting in absence of the enteric nervous system (ENS) and failure of intestinal transit postnatally. Treatment is by distal bowel resection, but neural cell replacement may be an alternative. We tested whether aneuronal (aganglionic) colon tissue from patients may be colonized by autologous ENS-derived cells. METHODS: Cells were obtained and cryopreserved from 31 HSCR patients from the proximal resection margin of colon, and ENS cells were isolated using flow cytometry for the NC marker p75 (nine patients). Aneuronal colon tissue was obtained from the distal resection margin (23 patients). ENS cells were assessed for NC markers immunohistologically and by quantitative reverse-transcription polymerase chain reaction, and mitosis was detected by ethynyl-2'-deoxyuridine labeling. The ability of human HSCR postnatal ENS-derived cells to colonize the embryonic intestine was demonstrated by organ coculture with avian embryo gut, and the ability of human postnatal HSCR aneuronal colon muscle to support ENS formation was tested by organ coculture with embryonic mouse ENS cells. Finally, the ability of HSCR patient ENS cells to colonize autologous aneuronal colon muscle tissue was assessed. RESULTS: ENS-derived p75-sorted cells from patients expressed multiple NC progenitor and differentiation markers and proliferated in culture under conditions simulating Wnt signaling. In organ culture, patient ENS cells migrated appropriately in aneural quail embryo gut, and mouse embryo ENS cells rapidly spread, differentiated, and extended axons in patient aneuronal colon muscle tissue. Postnatal ENS cells derived from HSCR patients colonized autologous aneuronal colon tissue in cocultures, proliferating and differentiating as neurons and glia. CONCLUSIONS: NC-lineage cells can be obtained from HSCR patient colon and can form ENS-like structures in aneuronal colonic muscle from the same patient.

BACKGROUND: Docetaxel is an effective therapy for metastatic castration-resistant prostate cancer (mCRPC); however, many patients experience febrile neutropenia (FN) and cease treatment early due to toxicity. It is not known whether lower dose (LD) q3-weekly docetaxel impacts toxicity or efficacy. METHODS: Multicenter retrospective study included 166 patients with mCRPC who received q3-weekly docetaxel between 2010 and 2015. Demographic, disease, chemotherapy (standard dose, SD > 60 mg/m2 vs LD ≤ 60 mg/m2 ) and toxicity data were collected. Univariable and multivariable logistic and competing risk regression models evaluated docetaxel-dose association with FN and early treatment cessation (ETC) due to toxicity. Associations between dose and efficacy end points were also evaluated. Analyses were repeated employing inverse propensity score weights. RESULTS: Patients who received LD docetaxel (28.9%) were older with poorer Eastern Cooperative Oncology Group (ECOG) status. Fifteen percent of patients experienced FN, with a nonsignificant trend to lower incidence in the LD group (multiple adjusted odds ratio [OR] = 0.42; P = 0.21). Neither baseline patient nor prior treatment factors were predictive of FN. ETC due to toxicity occurred in 35%, with risk associated with increasing age, comorbidity count and poorer ECOG. There was no difference between LD and SD with respect to ETC due to toxicity, in unweighted and weighted analyses (LD vs SD, multivariable weighted hazard ratio [HR] = 1.47; P = 0.08). LD was associated with reduced prostate-specific antigen (PSA) response (50% vs 66.1%, multivariable weighted HR = 0.54; P = 0.03) and overall survival (median 7.9 vs 13.8 months, multivariable weighted HR = 2.19; P < 0.0001). CONCLUSIONS: LD docetaxel for mCRPC did not mitigate the risk of FN or ETC due to toxicity. Dose reduction may result in poorer PSA response and survival.

BACKGROUND: Transcutaneous electrical stimulation (TES) using interferential current (IFC) is a new therapeutic treatment for constipation. Clinical studies show that TES-IFC for 3-6 months improves colonic transit, but it is not clear if short-term stimulation affects transit or the effect requires longer to develop. The aim of this study was to determine if TES-IFC for only four days affects oral-rectal transit time in healthy pigs. METHODS: Twenty-two 4-5-week old large white female piglets had transit studies during week 4 and week 5 by placing a capsule containing 18 radiopaque plastic markers in the esophagus under anesthetic followed by x-rays at 6, 30, 54, and 78 hours. Animals were randomly assigned to active or control groups. The active group received TES for 30 min daily for four days. Interferential current was applied through four electrodes (4 × 4 cm), with two para-spinal just below the last rib and two on the belly at the same level. Stimulation was at 4000 Hz and 4080-4160 Hz with currents crossing through the abdominal cavity. RESULTS: Whole bowel transit times ranged from 7.7 to 72.2 hours, stomach transit from <1 to 63 hours, and bowel with rectum transit time from 5 to 53 hours. Transit times were the same for the control (median 28.4 hours) and TES-IFC (23.0 hours) groups in the prestimulation and stimulation weeks (control 23.0, TES-IFC 19.8 hours) with no change within or between groups. CONCLUSION: Four days of half-hour TES-IFC daily in healthy 5-week-old piglets did not change oral-rectal transit time.

BACKGROUND: The sickest Australians are often those belonging to non-privileged groups, including Indigenous Australians, gay, lesbian, bisexual, transsexual, intersex and queer people, people from culturally and linguistically diverse backgrounds, socioeconomically disadvantaged groups, and people with disabilities and low English literacy. These consumers are not always engaged by, or included within, mainstream health services, particularly in rural Australia where health services are limited in number and tend to be generalist in nature. OBJECTIVE: The aim of this study was to present a new approach for improving the sociocultural inclusivity of mainstream, generalist, rural, health care organisations. DESIGN: This approach combines a modified Continuous Quality Improvement framework with Participatory Action Research principles and Foucault's concepts of power, discourse and resistance to develop a change process that deconstructs the power relations that currently exclude marginalised rural health consumers from mainstream health services. It sets up processes for continuous learning and consumer responsiveness. RESULTS: The approach proposed could provide a Continuous Quality Improvement process for creating more inclusive mainstream health institutions and fostering better engagement with many marginalised groups in rural communities to improve their access to health care. CONCLUSION: The approach to improving cultural inclusion in mainstream rural health services presented in this article builds on existing initiatives. This approach focuses on engaging on-the-ground staff in the need for change and preparing the service for genuine community consultation and responsive change. It is currently being trialled and evaluated.

OBJECTIVE: To examine the effects of dominant knowledge in rural health, including how they shape issues central to rural health. In particular, this article examines the roles of: (i) deficit knowledge of rural health workforce; (ii) dominant portrayals of generalism; and (iii) perceptions of inferiority about rural communities in maintaining health disparities between rural- and metropolitan-based Australians. DESIGN: A Foucauldian framework is applied to literature, evidence, case studies and key messages in rural health. Three scenarios are used to provide practical examples of specific knowledge that is prioritised or marginalised. RESULTS: The analysis of three areas in rural health identifies how deficit knowledge is privileged despite it undermining the purpose of rural health. First, deficit knowledge highlights the workforce shortage rather than the type of work in rural practice or the oversupply of workforce in metropolitan areas. Second, the construction of generalist practice as less skilled and more monotonous undermines other knowledge that it is diverse and challenging. Third, dominant negative stereotypes of rural communities discourage rural careers and highlight undesirable aspects of rural practice. CONCLUSION: The privileging of deficit knowledge pertaining to rural health workforce, broader dominant discourses of generalism and the nature of rural Australian communities reproduces many of the key challenges in rural health today, including persisting health disparities between rural- and metropolitan-based Australians. To disrupt the operations of power that highlight deficit knowledge and undermine other knowledge, we need to change the way in which rural health is currently constructed and understood.

INTRODUCTION: The need to measure reporting workload in teaching departments remains a current pertinent need. In Australia, the Pitman-Jones reporting RVUs have been in the public domain since 2003 (revised in 2009). These are expressed in arbitrary units. In New Zealand, single-site Christchurch Hospital reporting times have been validated and placed in the public domain. Concurrently, the RANZCR has been developing a formulaic descriptor lexicon for imaging studies (the Body System Framework). There is a need to bring these three strands of work together into a common public resource. In 2015, under the auspices of the Chief Accreditation Officer, RANZCR convened the Radiologist Workload Working Group. The goal of the group was to develop a robust method of measuring radiologist workload in teaching departments in Australia and New Zealand for the RANZCR accreditation processes of teaching departments as training sites. This paper concerns itself with one aspect of the group's work, namely reaching a consensus on radiologist study ascribable times for common imaging studies. METHOD: The BSF examination descriptors were reduced to a smaller, generic dataset of descriptors at the expense of loss of specificity. BSF study ascribable times had been previously obtained by stopwatch observation. The dataset was harmonized with the Christchurch descriptors to ensure commonality of case mix. The two lead authors reached an approximate consensus study ascribable time for each descriptor in agreement with the BSF and Christchurch data. Specifically, the Christchurch reporting times were relied on extensively to validate the new dataset's study ascribable times. The first draft of descriptors and times was tabled at the meetings of the RANZCR Radiologist Workload Working Group, and was progressively refined by iterative consensus. RESULTS: The output of the Radiologist Workload Working Group comprises a simplified modality-based table of robust descriptors and 'best estimate' corresponding study ascribable times. These can be used with the extant Pitman-Jones methodology in order to estimate the reporting workload of a medical imaging teaching department in units of time. As a first for Australia and New Zealand, nuclear medicine and PET study ascribable times have been incorporated and balanced against radiology study ascribable times. CONCLUSION: The RANZCR 2016 study ascribable times are ready for use by the Australian and New Zealand radiologist and nuclear medicine specialist community. We hope these times will also stimulate further data collection in our two countries towards a robust, bi-national study ascribable times database.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an incurable, chronic condition that leads to significant morbidity and mortality, with most patients dying in hospital. While diagnostic tests are important for actively managing patients during hospital admissions, the balance between benefit and harm should always be considered. This is particularly important when patients reach the end-of-life, when the focus is to reduce burdensome interventions. This study aimed to examine the use of diagnostic testing in a cohort of people with COPD who died in hospital. METHODS: Retrospective medical record audits were completed at two Australian hospitals (Royal Melbourne Hospital and Northeast Health Wangaratta), with all patients who died from COPD over twelve years between 1/1/2004 and 31/12/2015 included. RESULTS: Three hundred and forty-three patients were included, with a median of 11 diagnostic testing episodes per patient. Undergoing higher numbers of diagnostic tests was associated with younger age, ICU admission and non-invasive ventilation use. Reduced testing was associated with recent hospital admission for COPD, domiciliary oxygen use and a prior admission with documentation limiting medical treatment. Most patients underwent diagnostic tests in the last two days of life, and 12% of patients had ongoing diagnostic tests performed after a documented decision was made to change the goal of care to provide comfort care only. CONCLUSION: There were missed opportunities to reduce the burden of diagnostic tests and focus on comfort at the end of life. Increased physician education regarding communication and end-of-life care, including recognising active dying may address these issues. This article is protected by copyright. All rights reserved.

Background and objective: By adopting a trauma-informed approach to care at the organisational and clinical levels, health care systems and providers can enhance the quality of care that they deliver and improve health outcomes for individuals with a trauma history. This study aimed to explore the trauma-related knowledge, attitudes awareness, practice, competence and confidence of health service staff from three small rural health services in Victoria, Australia, and examine their self-reported capacity to respond to clients with a trauma history.Methods: Staff from each site were invited to complete a paper-based survey. The survey included demographic information and questions related to knowledge and understanding of trauma, experience of trauma-informed care and confidence engaging in, and perceived importance of, trauma-informed practices. Results: The respondents were predominately nurses. Results showed that 16% of respondents had undertaken training in trauma-informed care and 44% disagreed that they had an understanding of trauma-informed practices. There were high levels of agreement for statements related to knowledge and understanding of trauma and low levels of agreement with statements related to experience of trauma-informed care. More than 70% of respondents reported that they had little knowledge of the principals of trauma-informed care, and little experiencing with practicing trauma-informed care.Discussion and conclusions: Overall, the survey results showed that staff were trauma-aware, but supported the need for more education and training in trauma-informed practices and improved organisational approaches to support trauma-informed approaches. It is important for organisations to shift from being trauma aware to being trauma-informed, by building foundational awareness of these practices and reinforcement through continuing education.

BACKGROUND: The incremental value of 18FDG PET/CT in patients with breast cancer (BC) compared to conventional imaging (CI) in clinical practice is unclear. The aim of this study was to evaluate the management impact and prognostic value of 18 F-FDG PET/CT in this setting. METHODS: Sixty-three patients who were referred to our institution for suspicion of BC relapse were retrospectively enrolled. All patients had been evaluated with CI and underwent PET/CT. At a median follow-up of 61 months, serial clinical, imaging and pathologic results were obtained to validate diagnostic findings. Overall Survival (OS) was estimated using Kaplan Meier methods and analyzed using the Cox proportional hazards regression models. RESULTS: Forty-two patients had a confirmed relapse with 37 (88%) positive on CI and 40 (95%) positive on PET/CT. When compared with CI, PET/CT had a higher negative predictive value (86% versus 54%) and positive predictive value (95% versus 70%). The management impact of PET/CT was high (change of treatment modality or intent) in 30 patients (48%) and medium (change in radiation treatment volume or dose fractionation) in 6 patients (9%). Thirty-nine patients (62%) died during follow-up. The PET/CT result was a highly significant predictor of OS (Hazard Ratio [95% Confidence Interval] =4.7 [2.0-10.9] for PET positive versus PET negative for a systemic recurrence; p = 0.0003). In a Cox multivariate analysis including other prognosis factors, PET/CT findings predicted survival (p = 0.005). In contrast, restaging by CI was not significant predictor of survival. CONCLUSION: Our study support the value of 18 F-FDG PET/CT in providing incremental information that influence patient management and refine prognostic stratification in the setting of suspected recurrent breast cancer.