Citations

The following describes a case of isolated visceral angioedema related to an angiotensin II receptor blocker (ARB) medication. Additionally, we discuss the pathophysiology of drug-induced angioedema, various presentations that can be encountered, and the leading theorized mechanisms of how renin-angiotensin-aldosterone system (RAAS) blocking medications lead to angioedema. The goal of sharing this case is to help increase awareness of the possibility of ARB-induced angioedema and to recommend keeping visceral angioedema as part of the differential diagnosis when presented with a patient who is taking an angiotensin converting enzyme inhibitor (ACEI) or ARB medication that is experiencing gastrointestinal symptoms of unclear etiology.

Abstract INTRODUCTION The timing of plasma biomarker changes is not well understood. The goal of this study was to evaluate the temporal co‐evolution of plasma and positron emission tomography (PET) Alzheimer's disease (AD) biomarkers. METHODS We included 1408 Mayo Clinic Study of Aging and Alzheimer's Disease Research Center participants. An accelerated failure time (AFT) model was fit with amyloid beta (Aβ) PET, tau PET, plasma p‐tau217, p‐tau181, and glial fibrillary acidic protein (GFAP) as endpoints. RESULTS Individual timing of plasma p‐tau progression was strongly associated with Aβ PET and GFAP progression. In the population, GFAP became abnormal first, then Aβ PET, plasma p‐tau, and tau PET temporal meta‐regions of interest when applying cut points based on young, cognitively unimpaired participants. DISCUSSION Plasma p‐tau is a stronger indicator of a temporally linked response to elevated brain Aβ than of tau pathology. While Aβ deposition and a rise in GFAP are upstream events associated with tau phosphorylation, the temporal link between p‐tau and Aβ PET was the strongest. Highlights Plasma p‐tau progression was more strongly associated with Aβ than tau PET. Progression on plasma p‐tau was associated with Aβ PET and GFAP progression. P‐tau181 and p‐tau217 become abnormal after Aβ PET and before tau PET. GFAP became abnormal first, before plasma p‐tau and Aβ PET.

Purpose To develop a culturally-tailored American Indian/Alaska Native (AI/AN) women’s Facebook group supporting opioid recovery as an adjunct to medication. Design Community-based, qualitative approach. Setting Minnesota, U.S. Participants AI/AN women in opioid recovery, interested parties, and a Community Advisory Committee (CAC) of AI/AN women with lived experience, health care providers, and community members. Intervention We developed evidence-based content focusing on stress/trauma and substance use, mindfulness, responding to triggers, and supportive community resources. Additional content centered on AI/AN culture was also selected. Method Interviews were conducted by two women, then transcribed and coded using content analysis with NVivo software. Results were presented to CAC for further content refinement. Results CAC members (n = 10) guided study methods, intervention development, and dissemination activities. 14 AI/AN women (mean age 36.4 years; mean 6.7 months opioid abstinence) and 12 interested parties (7 men, 5 women) were receptive to an AI/AN gender-specific Facebook group, preferring content with AI/AN people and/or text resonating with AI/AN culture (e.g., Native traditions, family, personal stories, historical trauma). Recommendations included (1) protect confidentiality, (2) retain positivity, (3) incorporate resources and exercises to build coping skills, and (4) moderators should be authentic and relatable to build trust. Conclusions Our approach provides a model for developing culturally tailored, appealing and effective social media interventions to support AI/AN women in recovery from opioid use disorder.

Abstract Glioblastoma (GBM) is the most devastating and common form of primary brain cancer in adults. Tumor location plays a significant role in patient prognosis; in particular, GBM tumors contacting the lateral ventricles (LVs) are more aggressive than LV-distal counterparts. This may be due to interaction of tumors with unique features of the LV microenvironment, including the cerebrospinal fluid (CSF) and neural progenitor cells (NPCs) of the subventricular zone. Despite LV contact having a role on tumor malignancy, studies using bulk tumor samples to identify molecular contributors to LV-contacting prognosis have been only moderately successful, in large part due to intratumoral heterogeneity. Here, we leverage intraoperative surgical navigation to collect matched biopsies of adult LV-contacting primary GBM at locations proximal (< 2 cm) and distal ( > 2 cm) from the LV. Matched samples were collected from ten patients with equal sex distribution and an age range of 46 to 81 years. RNA sequencing of biopsies revealed a localized transcriptional signature of gene expression in LV-proximal locations. These genes include those identified to be associated with GBM malignancy and upregulated in primary GBM cells by CSF exposure or co-culture with NPCs, such as SERPINA3, CD44, and CTSB, as well as many newly identified genes. Implicated biological pathways involved in this transcriptional signature involve inflammation, chemotaxis, Notch signaling, angiogenesis, integrin signaling, and more. The top 50 upregulated genes by LV-proximity of GBM were used to cluster patient transcriptomes from the TCGA GBM database and evaluate the contribution to patient outcome. This analysis revealed a cluster with significantly extended overall survival that displayed a general downregulation of LV-proximity genes. Ultimately, these studies provide evidence that regional tumoral analysis is essential in identifying molecular signatures associated with microenvironmental influence, and that LV-contacting GBM has regional gene expression changes in many genes associated with malignancy.

Abstract Methylation profiling of brain tumors has revealed novel clusters whose biological and clinical significance is unknown. These include three entities termed by the 12.5 version of the Heidelberg methylation classifier as adult-type diffuse high grade glioma, IDH-wildtype, subtype B (HGG_B), subtype E (HGG_E), and subtype F (HGG_F). We have identified 75 cases belonging to these groups: HGG_B (25 cases, 32% female), HGG_E (40 cases, 42% female), and HGG_F (18 cases, 33% female). Although originally characterized as “adult-type,” we find that 70% of HGG_E cases are pediatric, with a median age at diagnosis of 11 years. HGG_B cases are predominantly seen in young adults, and HGG_F in older adults. The histology varies among methylation classes, with HGG_B cases demonstrating high-grade, predominantly astrocytic, morphology, while HGG_E cases demonstrate high-grade glial histology with distinct nuclear features, and HGG_F cases show highly infiltrative but lower grade glial morphology. Patient outcome data obtained to date shows a collective median survival exceeding 5 years, suggesting re-consideration of the proposed grading for these tumors. MGMT promoter methylation differs across the HGG_B (0%), HGG_E (12%), and HGG_F (0%) subtypes. Mutational analyses show enrichment of TERT promoter mutations in the HGG_F group, while HGG_E samples are enriched for tumors with POLE mutations and elevated tumor mutation burden. HGG_E tumors show epigenetic similarity to pediatric high-grade diffuse gliomas (pedHGG_RTK1A); we therefore propose that HGG_E be considered a pediatric-type HGG. HGG_B tumors show demographic and genomic similarities to high-grade astrocytomas with piloid features, including a subset of cases with CDKN2A/2B loss and ATRX mutation. HGG_F separate into two groups dictated by brain location, and despite the presence of TERT promoter mutations, appear distinct from GBMs. Overall, our work represents an initial effort to understand the morphologic, genomic and clinical characteristics of these previously uncharacterized subtypes of gliomas.

The current study evaluated work- and client-related burnout, perceived stress, and race-based stress with a focus on Black, Indigenous, or Persons of Color (BIPOC) mental health providers. An online survey ( n = 82) was distributed in the United States between July 17, 2020, and November 5, 2020. Demographic variables, racial discrimination during coronavirus disease 2019 (COVID-19), perceived stress, and the coping variables were assessed. The majority of respondents were women (85%), BIPOC identifying (72%), aged 25 to 34 years (43%), psychologists (50%), and had been practicing for 9 years. In total, 68% and 27% of providers reported moderate to severe work- and client-related burnout, respectively. Another 87% reported moderate to high stress. Factors associated with a higher level of burnout include being younger, having fewer years of experience, and being a social worker or family therapist. Among BIPOC providers, greater experiences of racial discrimination were associated with higher work-related burnout and stress. Greater use of maladaptive coping was associated with higher burnout and stress, yet we found no associations with the use of adaptive coping. Racial discrimination during COVID-19 was significantly associated with work-related burnout and perceived stress within a sample of predominantly BIPOC mental health providers. These findings reinforce the need for more focused support for mental health providers to ensure a healthy and resilient future workforce.

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Factor VII (FVII) is an important, vitamin K-dependent clotting factor. Acquired FVII deficiency is a rare entity that is associated with serious bleeding complications. We report a case of acquired FVII deficiency in a patient with recurrent chronic myeloid leukemia in blast crisis who developed bilateral retinal hemorrhages. The coagulopathy was corrected with the initiation of chemotherapy and subsequent reduction in peripheral blast count.