"Pain is not typically taken into consideration due to him being nonverbal"- emergency department experiences among persons with disabilities: a mixed methods study in Kingston, Ontario.

Background: Persons with disabilities (PWD) are more likely to visit the emergency department (ED) and often have complex health needs when accessing care in the ED. Yet there is limited understanding of ED care experiences among PWD, especially in a Canadian context. The aim of this study was to examine the ED care experiences of PWD in contrast to a comparison group in Kingston, Ontario to better understand their health care needs. Methods: A mixed-methods study with a community-based participatory approach examining participants' past ED care experiences (within 24 months) was conducted in Kingston, ON. Quantitative data from those with disabilities and those from the comparison group were compared using chi squared tests to identify differences between groups. An inductive and deductive thematic analysis approach was used to identify themes in the shared qualitative data. Convergence of findings across quantitative and qualitative data was undertaken. Results: A total of 175 participants identified as having a disability. In contrast with the comparison group (N = 949), PWD were more likely to report being given too little attention to their needs (p < 0.001), that it was more important to be treated with kindness/respect than to receive the best possible medical care (p < 0.001), to report feelings of disrespect and/or judgement (p < 0.001), and that better understanding of personal identity/situation/culture and better communication would improve ED care. Qualitative analysis highlighted the following themes: poor communication between PWD and health care providers (HCP), compassionate medical care received, perceived HCP negative attitudes/beliefs related to having a disability and substance misuse, and perceived HCP lack of knowledge/skill to treat the unique health needs of PWD. Conclusion: Findings highlight the need to improve ED care for PWD. Future quality improvement initiatives should focus on incorporating a deeper understanding of disability into medical education and emergency medicine (EM) residency education, designing curricula that emphasize cultural humility, and implementing community-based placements providing opportunities for health professionals to work with and learn from PWD.

Bridging the gap between in vitro and in vivo models: a way forward to clinical translation of mitochondrial transplantation in acute disease states.

Mitochondrial transplantation and transfer are being explored as therapeutic options in acute and chronic diseases to restore cellular function in injured tissues. To limit potential immune responses and rejection of donor mitochondria, current clinical applications have focused on delivery of autologous mitochondria. We recently convened a Mitochondrial Transplant Convergent Working Group (CWG), to explore three key issues that limit clinical translation: (1) storage of mitochondria, (2) biomaterials to enhance mitochondrial uptake, and (3) dynamic models to mimic the complex recipient tissue environment. In this review, we present a summary of CWG conclusions related to these three issues and provide an overview of pre-clinical studies aimed at building a more robust toolkit for translational trials.

B-cell characteristics define HCV reinfection outcome.

BACKGROUND & AIMS: In individuals highly exposed to HCV, reinfection is common, suggesting that natural development of sterilising immunity is difficult. In those that are reinfected, some will develop a persistent infection, while a small proportion repeatedly clear the virus, suggesting natural protection is possible. The aim of this study was to characterise immune responses associated with rapid natural clearance of HCV reinfection. METHODS: Broad neutralising antibodies (nAbs) and Envelope 2 (E2)-specific memory B cell (MBC) responses were examined longitudinally in 15 individuals with varied reinfection outcomes. RESULTS: Broad nAb responses were associated with MBC recall, but not with clearance of reinfection. Strong evidence of antigen imprinting was found, and the B-cell receptor repertoire showed a high level of clonality with ongoing somatic hypermutation of many clones over subsequent reinfection events. Single-cell transcriptomic analyses showed that cleared reinfections featured an activated transcriptomic profile in HCV-specific B cells that rapidly expanded upon reinfection. CONCLUSIONS: MBC quality, but not necessarily breadth of nAb responses, is important for protection against antigenically diverse variants, which is encouraging for HCV vaccine development. IMPACT AND IMPLICATIONS: HCV continues to have a major health burden globally. Limitations in the health infrastructure for diagnosis and treatment, as well as high rates of reinfection, indicate that a vaccine that can protect against chronic HCV infection will greatly complement current efforts to eliminate HCV-related disease. With alternative approaches to testing vaccines, such as controlled human inoculation trials under consideration, we desperately need to identify the correlates of immune protection. In this study, in a small but rare cohort of high-risk injecting drug users who were reinfected multiple times, breadth of neutralisation was not associated with ultimate clearance of the reinfection event. Alternatively, characteristics of the HCV-specific B-cell response associated with B-cell proliferation were. This study indicates that humoral responses are important for protection and suggests that for genetically very diverse viruses, such as HCV, it may be beneficial to look beyond just antibodies as correlates of protection.

"I am the doctor": gender-based bias within the clinical practice of emergency medicine in Canada-a thematic analysis of physician and trainee interview data.

OBJECTIVES: While women comprise about half of current Canadian medical students and physicians, only 31% of emergency medicine physicians identify as women and women trainees are less likely to express interest in emergency medicine compared to men. Gender-based bias continues to negatively impact the career choice, progress, and well-being of women physicians/trainees. Although instances of gender-based bias are well documented within other medical specialties, there remains a gap in the literature addressing the role of gender specific to the Canadian emergency medicine clinical environment. METHODS: Using a qualitative study with a thematic analytical approach, participants were purposively and snowball sampled from a cross-section of centers across Canada and included emergency medicine attending physicians and trainees. A thematic analysis using an inductive and deductive approach was undertaken. All data were double coded to improve study trustworthiness. Descriptive statistics were used to characterize the study population. RESULTS: Thirty-four individuals (17 woman-identifying and 17 man-identifying) from 10 different institutions across 4 provinces in Canada participated in the study. Six themes were identified: (1) women experience gender bias in the form of microaggressions; (2) women experience imposter syndrome and question their role in the clinical setting; (3) more women provide patient care to women patients and vulnerable populations; (4) gender-related challenges with family planning and home responsibilities affect work-life balance; (5) allyship and sponsorship are important for the support and development of women physicians and trainees; and (6) women value discussing shared experiences with other women to debrief situations, find mentorship, and share advice. CONCLUSIONS: Gender inequity in emergency medicine affects women-identifying providers at all levels of training across Canada. Described experiences support several avenues to implement change against perceived gender bias that is focused on education, policy, and supportive spaces. We encourage institutions to consider these recommendations to achieve gender-equitable conditions in emergency medicine across Canada.

ABSTRAIT: OBJECTIFS: Bien que les femmes représentent environ la moitié des étudiants et des médecins en médecine au Canada, seulement 31 % des médecins d'urgence qui s'identifient comme des femmes et des femmes stagiaires sont moins susceptibles d'exprimer leur intérêt pour la médecine d'urgence que les hommes. Les préjugés fondés sur le sexe continuent d'avoir une incidence négative sur le choix de carrière, les progrès et le bien-être des femmes médecins/stagiaires. Bien que les cas de biais fondés sur le sexe soient bien documentés dans d'autres spécialités médicales, il reste une lacune dans la documentation traitant du rôle du sexe propre au milieu clinique de la médecine d'urgence au Canada. MéTHODES: À l'aide d'une étude qualitative avec une approche analytique thématique, les participants ont été échantillonnés à dessein et en boule de neige dans un échantillon représentatif de centres à travers le Canada et comprenaient des médecins urgentistes et des stagiaires. Une analyse thématique utilisant une approche inductive et déductive a été entreprise. Toutes les données ont été codées en double pour améliorer la fiabilité de l'étude. Des statistiques descriptives ont été utilisées pour caractériser la population étudiée. RéSULTATS: Trente-quatre personnes (17 femmes et 17 hommes) de 10 établissements différents de quatre provinces canadiennes ont participé à l'étude. Six thèmes ont été cernés : (1) les femmes sont victimes de préjugés sexistes sous la forme de microagressions; (2) les femmes sont victimes du syndrome d'imposteur et remettent en question leur rôle dans le milieu clinique; (3) plus de femmes prodiguent des soins aux patientes et aux populations vulnérables; (4) les défis liés au genre que posent la planification familiale et les responsabilités familiales ont une incidence sur l'équilibre entre le travail et la vie personnelle; (5) l'alliance et le parrainage sont importants pour le soutien et le perfectionnement des femmes médecins et stagiaires; (6) les femmes apprécient de discuter des expériences partagées avec d'autres femmes pour faire le point sur des situations, trouver du mentorat et partager des conseils. CONCLUSIONS: L'inégalité entre les sexes en médecine d'urgence touche les fournisseurs de soins qui identifient les femmes à tous les niveaux de formation au Canada. Les expériences décrites appuient plusieurs avenues pour mettre en œuvre des changements contre les préjugés sexistes perçus qui sont axés sur l'éducation, les politiques et les espaces de soutien. Nous encourageons les établissements à tenir compte de ces recommandations afin de parvenir à des conditions équitables entre les sexes en médecine d'urgence partout au Canada.

Atypical memory B cell frequency correlates with antibody breadth and function in malaria immune adults.

Clinical immunity to malaria develops slowly after repeated episodes of infection and antibodies are essential in naturally acquired immunity against malaria. However, chronic exposure to malaria has been linked to perturbation in B-cell homeostasis with the accumulation of atypical memory B cells. It is unclear how perturbations in B cell subsets influence antibody breadth, avidity, and function in individuals naturally exposed to malaria. We show that individuals living in high malaria transmission regions in Ghana have higher Plasmodium falciparum merozoite antigen-specific antibodies and an increased antibody breadth score but lower antibody avidities relative to low transmission regions. The frequency of circulating atypical memory B cells is positively associated with an individual's antibody breadth. In vitro growth inhibition is independent of the ability to bind to free merozoites but associated with the breadth of antibody reactivity in an individual. Taken together, our data shows that repeated malaria episodes hamper the development of high avid antibodies which is compensated for by an increase in antibody breadth. Our results provide evidence to reinforce the idea that in regions with high malaria prevalence, repeated malaria infections lead to the broadening of antibody diversity and the continued presence of atypical memory B cell populations.

Three-Dimensional Morphometric Analysis of Anterior Cerebral Circulation Aneurysms.

This article assesses the association between anterior circulation morphometry and the presence of intracranial aneurysm using three-dimensional rotational angiography (3DRA). A retrospective analysis at a Peruvian academic medical center between December 2018 and February 2020 identified 206 patients with unruptured intracranial aneurysms and matched controls who underwent 3DRA. Angiographic images were obtained per standard of care, and measurements of the vasculature were performed using 3DRA vascular automated software. A total of 163 aneurysms and 43 control angiograms were evaluated. Women represented 82.5% of the cases and the mean age was 55.9 years (standard deviation ± 14.2). In multivariate analysis, five specific features were found to be statistically significant predictors for presence of an anterior circulation aneurysm: female sex (odds ratio [OR] = 2.71; p = 0.048), C-shape of the middle cerebral artery (MCA) (OR = 2.73; p = 0.018), distal internal carotid artery (ICA) diameter (OR = 3.42; p = 0.012), ICA bifurcation angle (OR = 1.02; p = 0.036), and length of the carotid siphon (OR = 1.08; p = 0.047). Features detected on 3DRA suggest morphological characteristics of the ICA and MCA may be predictive for intracranial aneurysm. Our findings build from prior reports by demonstrating five specific patient and imaging features associated with anterior circulation aneurysms. While 3DRA is the standard of care in many settings, medical centers with resource limitations may not have access to this technique. The demographic and morphological features identified in our study may have correlates that if detected on contrast computed tomography or magnetic resonance imaging studies, may be used to help screen for a higher level of care in select patients.

A comparison of computed tomography angiography and digital subtraction angiography for the diagnosis of penetrating cerebrovascular injury: a prospective multicenter study.

OBJECTIVE: In this research, the authors sought to characterize the incidence and extent of cerebrovascular lesions after penetrating brain injury in a civilian population and to compare the diagnostic value of head computed tomography angiography (CTA) and digital subtraction angiography (DSA) in their diagnosis. METHODS: This was a prospective multicenter cohort study of patients with penetrating brain injury due to any mechanism presenting at two academic medical centers over a 3-year period (May 2020 to May 2023). All patients underwent both CTA and DSA. The sensitivity and specificity of CTA was calculated, with DSA considered the gold standard. The number of DSA studies needed to identify a lesion requiring treatment that had not been identified on CTA was also calculated. RESULTS: A total of 73 patients were included in the study, 33 of whom had at least 1 penetrating cerebrovascular injury, for an incidence of 45.2%. The injuries included 13 pseudoaneurysms, 11 major arterial occlusions, 9 dural venous sinus occlusions, 8 dural arteriovenous fistulas, and 6 carotid cavernous fistulas. The sensitivity of CTA was 36.4%, and the specificity was 85.0%. Overall, 5.6 DSA studies were needed to identify a lesion requiring treatment that had not been identified with CTA. CONCLUSIONS: Cerebrovascular injury is common after penetrating brain injury, and CTA alone is insufficient to diagnosis these injuries. Patients with penetrating brain injuries should routinely undergo DSA.

Procedimiento para la infusión de mitocondrias autólogas por la arteria carótida en el cerebro porcino

Las mitocondrias son organelas complejas que desempeñan un papel fundamental en la célula, la disfunción mitocondrial puede ocasionar daños celulares significativos o la muerte. Estudios previos han demostrado los prometedores efectos terapéuticos del trasplante de mitocondrias autólogas a un tejido cardiaco isquémico, sin embargo, pocos estudios han evaluado los efectos in vivo de la infusión de mitocondrias en el cerebro. El presente trabajo tiene como objetivo dar a conocer el procedimiento para la infusión vía carótida de mitocondrias autólogas en cerebros porcinos. Mediante esta técnica de infusión, proponemos que una administración selectiva y mínimamente invasiva es factible y puede proporcionar beneficios en el tratamiento de diversas patologías del sistema nervioso central.

Mitochondria are complex organelles that play a critical role within the cell; mitochondrial dysfunction can result in significant cell damage or death. Previous studies have demonstrated the promising therapeutic effects of autologous mitochondria transplantation into ischemic cardiac tissue; however, few studies have examined the in vivo effects of mitochondria infusion into the brain. The aim of this study is to report a procedure for carotid infusion of autologous mitochondria into porcine brains. By using this infusion technique, we propose that a selective and minimally invasive administration is feasible and may provide benefits in the treatment of various central nervous system disorders.