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.

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.

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.

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.

Patterns of breast reconstruction and the influence of a surgical multidisciplinary clinic.

BACKGROUND: Of the 40% of breast cancer patients who have a mastectomy as part of their surgical treatment, only approximately 29% have a breast reconstruction. In 2016, Alfred Health established a multidisciplinary surgical clinic with breast and plastic surgeons, aiming to improve interdisciplinary collaboration. This study aimed to assess the provision of breast reconstruction at an Australian tertiary public hospital and examine whether the multidisciplinary surgical clinic have improved our reconstructive service provision. METHODS: A retrospective cohort study of patients who underwent mastectomy at Alfred Health between October 2011 and September 2021 was conducted. Patients were divided into before and after groups, treated during the 5-year period before and after establishing the multidisciplinary clinic respectively. Demographic data, operative details, histopathology, and treatments were compared. RESULTS: Over the 10-year period, 423 mastectomies were performed for 351 patients. Of those, 153 patients underwent breast reconstruction, providing an overall reconstruction rate of 43.6%. There was a statistically significant increase in the breast reconstruction rate from 36.5% before to 53.4% after the creation of the multidisciplinary surgical clinic. Patient factors such as age and tumour receptor status did not differ significantly between the groups. CONCLUSION: The establishment of a surgical multidisciplinary clinic has led to a statistically significant increase in the rate of breast reconstruction from 36.5% to 53.4%, leading to improved healthcare provision for our patients. Factors identified to be associated with increased uptake in the reconstruction service include younger age and node negative disease.

Emergency department care experiences among people who use substances: a qualitative study.

BACKGROUND: People who use substances (PWUS) encounter significant barriers to accessing care for their complex health needs. As a result, emergency departments (EDs) often become the first point of healthcare access for many PWUS and are a crucial setting for the study of health inequities. This study aimed to understand the ED healthcare experiences of PWUS with the intent of informing ways of improving the delivery of equitable care. METHODS: This qualitative study was part of a larger cross-sectional, mixed-methods study that examined ED experiences among diverse underserved and equity-deserving groups (EDGs) within Kingston, Ontario, Canada. Participants shared and self-interpreted a story about a memorable ED or UCC visit within the preceding 24 months. Data from participants who self-identified as having substance use experiences was analyzed through inductive thematic analysis. RESULTS: Of the 1973 unique participants who completed the survey, 246 participants self-identified as PWUS and were included in the analysis. Most participants were < 45 years of age (61%), male (53%), and white/European (57%). 45% identified as a person with a disability and 39% frequently struggled to make ends meet. Themes were determined at the patient, provider, and system levels. PATIENT: history of substance use and experience of intersectionality negatively influenced participants' anticipation and perception of care. Provider: negative experiences were linked to assumption making, feelings of stigma and discrimination, and negative perceptions of provider care. Whereas positive experiences were linked to positive perceptions of provider care. System: timeliness of care and the perception of inadequate mental health resources negatively impacted participants' care experience. Overall, these themes shaped participants' trust of ED staff, their desire to seek care, and their perception of the care quality received. CONCLUSIONS: PWUS face significant challenges when seeking care in the ED. Given that EDs are a main site of healthcare utilization, there is an urgent need to better support staff in the ED to improve care experiences among PWUS. Based on the findings, three recommendations are proposed: (1) Integration of an equity-oriented approach into the ED, (2) Widespread training on substance use, and (3) Investment in expert resources and services to support PWUS.

Urgent care-seeking and injury severity for intimate partner violence during COVID-19: a Canadian retrospective chart review.

BACKGROUND: Early reports raised alarms that intimate partner violence (IPV) increased during the COVID-19 pandemic, but initial studies showed that visits to emergency departments (EDs) decreased. This study assessed the impact of the prolonged pandemic and its associated restrictions on both rates of urgent care-seeking and injury severity for IPV. METHODS: Data from the Kingston Health Sciences Centre's (KHSC) ED were utilized to compare IPV presentations during 'Pre-COVID' (December 17, 2018 - March 16, 2020) and 'COVID' (March 17, 2020 - June 16, 2021), as well as three periods of heightened local restrictions: 'Lockdown-1' (March 17 - June 12, 2020), 'Lockdown-2' (December 26, 2020 - February 10, 2021) and 'Lockdown-3' (April 8 - June 2, 2021). The primary outcomes were incidence rate of IPV visits and injury severity, which was assessed using the Clinical Injury Extent Score (CIES) and Injury Severity Score (ISS). RESULTS: A total of 128 individuals were included. This sample had mean age of 34 years, was comprised of mostly women (97%), and represented a variety of intimate relationship types. Some individuals presented multiple times, resulting in a total of 139 acute IPV presentations. The frequency of IPV visits during COVID was similar to the Pre-COVID time period (67 vs. 72; p = 0.67). Incidence rate was 13% higher during COVID, though this difference was non-significant (6.66 vs. 5.90; p = 0.47). IPV visit frequency varied across lockdown periods (11 in Lockdown-1, 12 in Lockdown-2 and 6 in Lockdown-3), with the highest incidence rate during Lockdown-2 (12.71). There were more moderate and severe injuries during COVID compared to Pre-COVID, but mean CIES was not statistically significantly different (1.91 vs. 1.69; p = 0.29), nor was mean ISS (11.88 vs. 12.52; p = 0.73). CONCLUSIONS: During the 15-months following the start of COVID-19, there were small, but non-significant increases in both incidence rate and severity of IPV presentations to the KHSC ED. This may reflect escalation of violence as pandemic restrictions persisted and requires further investigation.

Flow Diversion for the Treatment of Intracranial Aneurysms in a Peruvian Cohort: Experiences from a Limited-Resource Setting and Barriers to Implementation.

BACKGROUND: Stenting with flow diverter devices (FDDs) has increasingly emerged as a treatment for intracranial aneurysms. The use of FDDs in the developing world has not been described. METHODS: A retrospective review was performed of a cohort of patients who underwent flow diversion at 4 tertiary-care centers in Lima, Peru between January 2017 and June 2021. Demographics, clinical features, and aneurysm morphology were evaluated. Clinical outcomes were observed 3 months after discharge and occlusion rates were assessed 12 months after treatment. RESULTS: Sixty-nine patients (mean age, 46 ±14.5 years; 17% female) were treated with FDDs; 4% (n = 3) of the treated aneurysms were ruptured. Most aneurysms were saccular (n = 65; 94%), <10 mm in maximum size (n = 60; 87%), and located in the anterior circulation (n = 67; 97%). Minor complications, such as groin hematoma, occurred in 7 cases. No serious complications or deaths occurred. Patients' functional status was excellent (modified Rankin Scale score 0-1) in 99% (n = 66) at discharge and 100% (n = 67) at 3 months. Although some patients were lost to follow-up, complete occlusion was seen in 76% (n = 31) of 41 treated patients at 12 months. CONCLUSIONS: We report the largest multicenter experience of FDDs for cerebral aneurysm treatment in Peru, with reasonable outcomes that are comparable to other settings despite various challenges, suboptimal circumstances, and lack of resources.

Intraarterial Transplantation of Mitochondria After Ischemic Stroke Reduces Cerebral Infarction.

Background-: Transplantation of autologous mitochondria into ischemic tissue may mitigate injury caused by ischemia and reperfusion. Methods-: Using murine stroke models of middle cerebral artery occlusion, we sought to evaluate feasibility of delivery of viable mitochondria to ischemic brain parenchyma. We evaluated the effects of concurrent focused ultrasound activation of microbubbles, which serves to open the blood-brain barrier, on efficacy of delivery of mitochondria. Results-: Following intra-arterial delivery, mitochondria distribute through the stroked hemisphere and integrate into neural and glial cells in the brain parenchyma. Consistent with functional integration in the ischemic tissue, the transplanted mitochondria elevate concentration of adenosine triphosphate in the stroked hemisphere, reduce infarct volume and increase cell viability. Additional of focused ultrasound leads to improved blood brain barrier opening without hemorrhagic complications. Conclusions-: Our results have implications for the development of interventional strategies after ischemic stroke and suggest a novel potential modality of therapy after mechanical thrombectomy.

Characterization of SARS-CoV-2 humoral immune response in a subject with unique sampling: A case report.

BACKGROUND: The development of vaccine candidates for COVID-19, and the administration of booster vaccines, has meant a significant reduction in COVID-19 related deaths world-wide and the easing of global restrictions. However, new variants of SARS-CoV-2 have emerged with less susceptibility to vaccine induced immunity leading to breakthrough infections among vaccinated people. It is generally acknowledged that immunoglobulins play the major role in immune-protection, primarily through binding to the SARS-COV-2 receptor binding domain (RBD) and thereby inhibiting viral binding to the ACE2 receptor. However, there are limited investigations of anti-RBD isotypes (IgM, IgG, IgA) and IgG subclasses (IgG1-4) over the course of vaccination and breakthrough infection. METHOD: In this study, SARS-CoV-2 humoral immunity is examined in a single subject with unique longitudinal sampling. Over a two year period, the subject received three doses of vaccine, had two active breakthrough infections and 22 blood samples collected. Serological testing included anti-nucleocapsid total antibodies, anti-RBD total antibodies, IgG, IgA, IgM and IgG subclasses, neutralization and ACE2 inhibition against the wildtype (WT), Delta and Omicron variants. RESULTS: Vaccination and breakthrough infections induced IgG, specifically IgG1 and IgG4 as well as IgM and IgA. IgG1 and IgG4 responses were cross reactive and associated with broad inhibition. CONCLUSION: The findings here provide novel insights into humoral immune response characteristics associated with SARS-CoV-2 breakthrough infections.

Safety and radiologic clearance of chronic subdural hematoma after endovascular embolization using SQUID 18 in patients older than 80 years.

The aim of the study was to evaluate radiographic clearance and clinical outcomes in patients over age 80 who undergo SQUID 18 embolization of the middle meningeal artery (MMA) for the management of chronic subdural hematoma (cSDH). From April 2020 to October 2021, data were obtained from patients with cSDH who underwent MMA embolization at our institution. Clinical and radiological data including pre-operative and last follow-up CT scans were analyzed. Six embolization procedures were performed in five patients using SQUID 18, a liquid embolic agent. The median age was 83 years, and three subjects were female. Two of the six cases were recurrent hematomas. MMA embolization was achieved in 100% of cases. The median diameter of the hematoma at admission was 20 mm and at last follow-up was 5.3 mm, demonstrating statistically significant radiographic clearance (P = 0.043). There were no intra or post-operative complications. Mortality was not noted during observation period. SQUID MMA embolization safely and significantly reduced the hematoma diameter and offers an alternative treatment in patients older than 80 years with cSDH.

Lesbian, gay, bisexual, transgender and or queer patient experiences in Canadian primary care and emergency departments: a literature review.

This literature review synthesises existing evidence and offers a thematic analysis of primary care and emergency department experiences of lesbian, gay, bisexual, transgender, queer and/or any other sexual or gender minority (LGBTQ+) individuals in Canada. Articles detailing first-person primary or emergency care experiences of LGBTQ + patients were included from EMBASE, MEDLINE, PsycINFO and CINHAL. Studies published before 2011, focused on the COVID-19 pandemic, unavailable in English, non-Canadian, specific to other healthcare settings, and/or only discussing healthcare provider experiences were excluded. Critical appraisal was performed following title/abstract screening and full-text review by three reviewers. Of sixteen articles, half were classified as general LGBTQ + experiences and half as trans-specific experiences. Three overarching themes were identified: discomfort/disclosure concerns, lack of positive space signalling, and lack of healthcare provider knowledge. Heteronormative assumptions were a key theme among general LGBTQ + experiences. Trans-specific themes included barriers to accessing care, the need for self-advocacy, care avoidance, and disrespectful communication. Only one study reported positive interactions. LGBTQ + patients continue to have negative experiences within Canadian primary and emergency care - at the provider level and due to system constraints. Increasing culturally competent care, healthcare provider knowledge, positive space signals, and decreasing barriers to care can improve LGBTQ + experiences.

Emergency department care experiences among members of equity-deserving groups: quantitative results from a cross-sectional mixed methods study.

BACKGROUND: Emergency departments (EDs) serve an integral role in healthcare, particularly for vulnerable populations. However, marginalized groups often report negative ED experiences, including stigmatizing attitudes and behaviours. We engaged with historically marginalized patients to better understand their ED care experiences. METHOD: Participants were invited to complete an anonymous mixed-methods survey about a previous ED experience. We analysed quantitative data including controls and equity-deserving groups (EDGs) - those who self-identified as: (a) Indigenous; (b) having a disability; (c) experiencing mental health issues; (d) a person who uses substances; (e) a sexual and gender minority; (f) a visible minority; (g) experiencing violence; and/or (h) facing homelessness - to identify differences in their perspectives. Differences between EDGs and controls were calculated with chi squared tests, geometric means with confidence ellipses, and the Kruskal-Wallis H test. RESULTS: We collected a total of 2114 surveys from 1973 unique participants, 949 controls and 994 who identified as equity-deserving. Members of EDGs were more likely to attribute negative feelings to their ED experience (p < 0.001), to indicate that their identity impacted the care received (p < 0.001), and that they felt disrespected and/or judged while in the ED (p < 0.001). Members of EDGs were also more likely to indicate that they had little control over healthcare decisions (p < 0.001) and that it was more important to be treated with kindness/respect than to receive the best possible care (p < 0.001). CONCLUSION: Members of EDGs were more likely to report negative ED care experiences. Equity-deserving individuals felt judged and disrespected by ED staff and felt disempowered to make decisions about their care. Next steps will include contextualizing findings using participants' qualitative data and identifying how to improve ED care experiences among EDGs to make it more inclusive and better able to meet their healthcare needs.

Microsurgical and endovascular treatment of posterior inferior cerebellar artery aneurysms: a systematic review and meta-analysis.

INTRODUCTION: Posterior inferior cerebellar artery (PICA) aneurysms are uncommon vascular lesions of the posterior fossa. In addition to aneurysmal morphology, structural anatomic considerations may confer additional procedural risk, and as a result there is currently no consensus as to whether a surgical or endovascular approach offers greater safety and efficacy for patients. EVIDENCE ACQUISITION: We systematically examined peer-reviewed literature describing PICA aneurysm treatment planning from January 2000 to May 2021 using the PRISMA methodology. A meta-analysis of proportions was performed. Certainty of the evidence was assessed using the GRADE approach. EVIDENCE SYNTHESIS: Fifty-eight studies including 1673 PICA aneurysms were analyzed. Overall treatment occlusion rate was 97% (95% confidence interval [CI]: 93-100%) for surgery and 85% (95% CI: 78-92%) for endovascular therapy. The recurrence rate was 6% in the endovascular group and 1% for surgery. Overall morbidity and mortality were 16% and 7%, respectively. Intraoperative complications occurred in 9% of the surgical patients. CONCLUSIONS: Despite a large body of literature, analysis indicates that 62% of studies had moderate or serious risk of bias, suggesting very-low certainty results. Therefore, treatment via either approach should be determined on a case-by-case basis and according to institutional experience.

Machine Learning Analysis of the Cerebrovascular Thrombi Lipidome in Acute Ischemic Stroke.

ABSTRACT: OBJECTIVE: The aim of this study was to identify a signature lipid profile from cerebral thrombi in acute ischemic stroke (AIS) patients at the time of ictus. METHODS: We performed untargeted lipidomics analysis using liquid chromatography-mass spectrometry on cerebral thrombi taken from a nonprobability, convenience sampling of adult subjects (≥18 years old, n = 5) who underwent thrombectomy for acute cerebrovascular occlusion. The data were classified using random forest, a machine learning algorithm. RESULTS: The top 10 metabolites identified from the random forest analysis were of the glycerophospholipid species and fatty acids. CONCLUSION: Preliminary analysis demonstrates feasibility of identification of lipid metabolomic profiling in cerebral thrombi retrieved from AIS patients. Recent advances in omic methodologies enable lipidomic profiling, which may provide insight into the cellular metabolic pathophysiology caused by AIS. Understanding of lipidomic changes in AIS may illuminate specific metabolite and lipid pathways involved and further the potential to develop personalized preventive strategies.

Patient and Provider Emergency Care Experiences Related to Intimate Partner Violence: A Systematic Review of the Existing Evidence.

Intimate partner violence (IPV) is a public health problem that has devastating physical, psychological, and economic consequences. The emergency department (ED) is an important point of contact for individuals experiencing IPV. However, there are few studies synthesizing interactions between patients experiencing IPV and providers. We aimed to summarize the existing evidence regarding (1) ED care experiences of patients with a history of IPV and (2) experiences of ED providers interacting with them. The secondary aim of this review was to evaluate high-quality care barriers and facilitators and to elucidate common causes of care avoidance. A literature search of peer-reviewed electronic databases was undertaken. Inclusion criteria consisted of studies detailing IPV-related patient or provider experiences surrounding ED visits. Articles published before 2000 or unavailable in English/French were excluded. A total of 772 studies were screened, yielding a final number of 41 studies. Negative patient experiences arose from individual-, institutional-, and system-level issues, commonly including adverse provider behavior. Negative provider experiences stemmed from individual-, institutional-, and system-level issues, such as a lack of knowledge and lack of infrastructure. Facilitators to positive patient experiences included interacting with empathetic providers, having privacy, and receiving timely specialized care. Facilitators to positive provider experiences included feeling well-equipped to manage IPV and having policies leading to appropriate care. Negative ED care experiences reveal inadequate care quality, ultimately leading to secondary victimization of individuals experiencing IPV. This review also uncovered important literature gaps regarding experiences of those who identify as equity-deserving.

Scoping Review: Research Training During Medical School.

Fostering skills in research is important for medical schools. This scoping review examined undergraduate curricular structures devoted to research training and their outcomes. For the sixty papers meeting inclusion criteria, descriptive statistics and a thematic analysis were conducted. Forty (67%) articles described US programs, with 30 (50%) being mandatory. Timing of research training was variable across included studies with the majority (58%) describing embedded longitudinal curricula. Reported benefits included enhanced knowledge, improved research and writing skills, clarity around career plans, and mentoring relationships. There are many curricular structures for undergraduate research training, but no high-quality evidence to support particular designs.