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Christianne Hoey,1,2 Stanley K Liu1–3 1Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada; 2Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; 3Department of Radiation Oncology, University of Toronto, Toronto, ON M5S 3E2, Canada Abstract: Current risk stratification methods for prostate cancer – although they have seen marked improvements over the past decades – are far from perfect. Despite the significant utility of prostate-specific antigen as a biomarker to monitor for disease recurrence, it cannot predict which tumors will recur or recommend the best treatment for patients. Similarly, although biopsies are imperative for diagnosis and staging, they are saddled with limitations and risks. We must move toward a noninvasive biomarker that has predictive and prognostic efficacy. We therefore review the current literature on circulating miRNA biomarkers, apply their use to two significant clinical problems (ie, how limitations of prostate biopsies can impact diagnosis and treatment management, and the need to tailor treatment for a clinically heterogeneous disease), and evaluate how circulating miRNAs have inherent properties that make them ideal liquid biomarkers. We also outline current gaps in knowledge that must be addressed before they can be implemented into routine clinical practice. With further research on their function and validation of their biomarker utility in large prospective cohorts, circulating miRNAs will likely prove to be the liquid biopsies of tomorrow. Keywords: miRNA, biomarker, prostate cancer, risk stratification, serum, plasma

With a low incidence of Salmonella infection, salmonellosis is an uncommon problem in Scotland. It occurs in both immune-compromised and immune-competent patients. We present two cases of salmonellosis in immune-competent patients who had had a history of gastroenteritis. Diagnosis was delayed in one patient; however, both patients received appropriate treatment and made good recovery following their respective illnesses. Apart from acting as a reminder to consider salmonellosis as a differential diagnosis when managing patients with infective process, the cases also highlight the importance of concise history taking, and the importance of cultures-andsensitivities in managing infectious cases. [ABSTRACT FROM AUTHOR]

Six cases of tuberculous meningitis, all occurring in patients over the age of 65, are described. All patients presented with an acute illness, primarily with a confusional state. Headache was a symptom in only two patients and the cases were not confined to ethnic minority groups. The mortality was 50%. [ABSTRACT FROM PUBLISHER]

Abstract Background Neoplasms arising from Meckel's diverticulae reported in the literature are mainly carcinoid tumours, gastrointestinal stromal tumours, and gastric or intestinal adenocarcinomas. Case presentation We describe a 50-year-old man who presented with rectal bleeding and anaemia, later found to be caused by a pancreatic adenocarcinoma arising from ectopic pancreatic tissue in a Meckel's diverticulum. The tumour was unfortunately highly aggressive, and the patient passed away within 5 months of symptom onset. Conclusion We believe this is the first case of pancreatic adenocarcinoma in a Meckel's diverticulum to be reported in the literature. The diagnosis of Meckel's should be considered in patients with acute gastrointestinal complaints; when found incidentally at laparotomy, it should be carefully examined for any gross abnormality and resection should be considered.

Background: Little is known about factors that influence footwear selection by field hockey players., Methods: An online survey was used to collect data on participant demographics and physical characteristics, factors influencing footwear selection, perceptions regarding footwear design features on injury and performance, and experiences regarding usability. Nominal and ordinal data were described as absolute frequencies and relative frequencies. Free text responses were analysed using content analysis. Sex-related differences in quantitative and qualitative data were explored., Results: A total of 401 hockey players completed the survey. Participants reported that fit, comfort, support, and cushioning were the most important factors when selecting hockey footwear. Most hockey players believed that stud design could influence athletic performance (65%) and injury risk (63%) but reported having no preference on outsole design or stud shape. Most participants (63%) used hockey-specific footwear, but 46% of female hockey players did not, with 40% using trail running footwear instead. Qualitative analysis revealed that hockey players, particularly female participants, encounter difficulties finding properly fitting footwear. They desire more options for wide or narrow feet and face challenges in accessing suitable hockey shoes due to limited choices and availability., Conclusions: With over a third of field hockey players not using hockey-specific footwear, future research should attempt to understand the reasons and assess the impact of different footwear features on comfort, performance, injury risk, and usability., (© 2024 The Author(s). Journal of Foot and Ankle Research published by John Wiley & Sons Australia, Ltd on behalf of Australian Podiatry Association and The Royal College of Podiatry.)

Background: The use of antibiotics in mild to severe acute exacerbations of chronic obstructive pulmonary disease (COPD) remains controversial., Aim: To explore in-hospital antibiotic use in severe acute exacerbations of COPD (AECOPD), to analyze determinants of in-hospital antibiotic use, and to investigate its association with hospital length of stay (LOS) and in-hospital mortality., Methods: A retrospective, observational study was conducted in Ghent University Hospital. Severe AECOPD were defined as hospitalizations for AECOPD (ICD-10 J44.0 and J44.1) discharged between 2016 and 2021. Patients with a concomitant diagnosis of pneumonia or 'pure' asthma were excluded. An alluvial plot was used to describe antibiotic treatment patterns. Logistic regression analyses identified determinants of in-hospital antibiotic use. Cox proportional hazards regression analyses were used to compare time to discharge alive and time to in-hospital death between antibiotic-treated and non-antibiotic-treated AECOPD patients., Results: In total, 431 AECOPD patients (mean age 70 years, 63% males) were included. More than two-thirds (68%) of patients were treated with antibiotics, mainly amoxicillin-clavulanic acid. In multivariable analysis, several patient-related variables (age, body mass index (BMI), cancer), treatment-related variables (maintenance azithromycin, theophylline), clinical variables (sputum volume and body temperature) and laboratory results (C-reactive protein (CRP) levels) were associated with in-hospital antibiotic use independent of sputum purulence, neutrophil counts, inhaled corticosteroids and intensive care unit of which CRP level was the strongest determinant. The median hospital LOS was significantly longer in antibiotic-treated patients (6 days [4-10]) compared to non-antibiotic-treated patients (4 days [2-7]) (p < 0.001, Log rank test). This was indicated by a reduced probability of hospital discharge even after adjustment for age, sputum purulence, BMI, in-hospital systemic corticosteroid use and forced expiratory volume in one second (FEV 1 ) (adjusted hazard ratio 0.60; 95% CI 0.43; 0.84). In-hospital antibiotic use was not significantly associated with in-hospital mortality., Conclusions: In this observational study in a Belgian tertiary hospital, in-hospital antibiotic use among patients with severe AECOPD was determined by the symptom severity of the exacerbation and the underlying COPD severity as recommended by the guidelines, but also by patient-related variables. Moreover, in-hospital antibiotic use was associated with a longer hospital stay, which may be linked to their disease severity, slower response to treatment or 'harm' due to antibiotics., Trial Registration: Number: B670201939030; date of registration: March 5, 2019., (© 2023. The Author(s).)

Frailty is a common clinical syndrome that predisposes older adults to an increased risk of adverse health outcomes. With population aging, this will become an increasing challenge for the healthcare services; therefore, different models of healthcare training and provision are required to address these increasing demands. In Ireland, the National Clinical Programme for Older People (NCPOP) has partnered with The Irish Longitudinal Study on Ageing (TILDA) to deliver the National Frailty Education Programme. This demonstrates an innovative way in which evidence-based longitudinal research can be translated into clinical education and practice to improve patient care, following a Knowledge to Action (KTA) process. To the authors' knowledge, it is the first time that a longitudinal research study such as TILDA has employed such methods of translation and therefore, this collaboration could serve as an international model of translation and implementation for frailty and other areas of clinical priority.

Challenges exist in respect of people with intellectual disabilities who, with the increasing life expectancy, have a growing risk of age-related degenerative conditions. Changes in bone health are associated with increasing age and the bone health of people who have intellectual disabilities is well documented in the literature as being poor in comparison to the general population. A heel scan clinic was set up in an intellectual disability service as a service improvement initiative. There were 12 females and 17 males scanned using a heel scanner. Only 3 (10.3%) people with intellectual disabilities were in the normal bone mineral density (BMD) range. Peripheral BMD screening for people has been shown to provide important information about the bone health of people with intellectual disabilities which has prompted further treatment by general practitioners and has the potential to provide an accessible way to obtain information on the bone health of people with intellectual disabilities.

Background: Patients with metastatic breast cancer (MBC) are living longer, but the development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population., Methods: Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with human epidermal growth factor receptor-2 positive (HER2+), triple negative, and hormone receptor (HR)+/hormone receptor negative (HER2-) MBC; pooled overall estimates for incidence were calculated using random effects models., Results: 937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0-34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5-40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9-36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10-0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09-0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03-0.08) for patients with HR+/HER2- MBC., Conclusion: There is a high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Observational studies have suggested that HER2 inhibition with trastuzumab may be associated with an increased incidence of intracranial metastatic disease (IMD) due to its ability to prolong survival. We hypothesized that prolonged survival associated with dual-agent HER2 inhibition may be associated with an even higher incidence of IMD. This study pooled estimates of IMD incidence and survival among patients with HER2-positive breast cancer receiving dual- versus single-agent HER2 targeted therapy, as well as trastuzumab versus chemotherapy, observation, or another HER2-targeted agent. We searched PubMed, EMBASE, and CENTRAL from inception to 25 March 2020. We included randomized controlled trials that reported IMD incidence for patients with HER2-positive breast cancer receiving trastuzumab as the experimental or control arm irrespective of disease stage. Among 465 records identified, 19 randomized controlled trials (32,572 patients) were included. Meta-analysis of four studies showed that dual HER2-targeted therapy was associated with improved overall survival (HR 0.76; 95% CI, 0.66-0.87) and progression-free survival (HR 0.77; 95% CI, 0.68-0.87) compared to single HER2-targeted therapy, but the risk of IMD was similar (RR 1.03; 95% CI, 0.83-1.27). Our study challenges the hypothesis that prolonged survival afforded by improved extracranial disease control is associated with increased IMD incidence.

Since the initial reports surfaced of a novel coronavirus causing illness and loss of life in Wuhan, China, COVID-19 has rapidly spread across the globe, infecting millions and leaving hundreds and thousands dead. As hospitals cope with the influx of patients with COVID-19, new challenges have arisen as health-care systems care for patients with COVID-19 while still providing essential emergency care for patients with acute strokes and acute myocardial infarction. Adding to this complex scenario are new reports that patients with COVID-19 are at increased risk of thromboembolic complications including strokes. In this article, we detail our experience caring for acute stroke patients and provide some insight into neurointerventional workflow modifications that have helped us adapt to the COVID-19 era., (© 2020 Association for Radiologic & Imaging Nursing. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau.2019.11.25). PCB has a patent or multiple patients on prostate cancer biomarkers issued. The other authors have no conflicts of interest to declare.

Introduction: Conceptualisation of occupation requires understanding of subjective wellbeing and experiences of occupation. Opportunities for participation in productivity activities, such as employment, may be limited for people with intellectual disability (ID). An occupational wellbeing framework was recently re-imagined to focus on the subjective meaning of a person's occupational life rather than occupational performance. This study analysed experiences and possible benefits to occupational wellbeing of young adult men with ID in an intergenerational mentoring program based on Australian Men's Sheds using this revised occupational wellbeing framework., Methods: A qualitative approach was used to gather individual semi-structured interviews at the end of an intergenerational mentoring program to explore occupational wellbeing experiences. Eight individual mentees and five parents of mentees (n = 13) from the different Men's Sheds sites agreed to participate in an individual interview about their experiences of the program. All mentees were male aged between 17 and 24 years. Family members included four female mothers and one male father. Data were highlighted, selected and deductively coded using content analysis according to the five occupational wellbeing domains of the framework., Results: Mentees reflected upon their experience with their mentor, the program, activities and environment of the Men's Shed. Findings were organised in relation to each of the five domains of occupational wellbeing, including contentment, competence, belonging, identity and autonomy. Experiences of mentees and their family members reflected the positive impact of participation on each domain and occupational wellbeing, including opportunities for socialisation outside of the program, mastery of skills and knowledge and validation of belief in self., Conclusion: Mentees involved in an intergenerational mentoring program in Australian Men's Sheds report benefits of participation in activities that foster and increase occupational wellbeing experiences. The experience of such domains should be considered when attempting to understand the quality of life and function for people with disabilities., (© 2019 Occupational Therapy Australia.)