Citations

AbstractThis article provides recommendations for implementing QSM for clinical brain research. It is a consensus of the International Society of Magnetic Resonance in Medicine, Electro‐Magnetic Tissue Properties Study Group. While QSM technical development continues to advance rapidly, the current QSM methods have been demonstrated to be repeatable and reproducible for generating quantitative tissue magnetic susceptibility maps in the brain. However, the many QSM approaches available have generated a need in the neuroimaging community for guidelines on implementation. This article outlines considerations and implementation recommendations for QSM data acquisition, processing, analysis, and publication. We recommend that data be acquired using a monopolar 3D multi‐echo gradient echo (GRE) sequence and that phase images be saved and exported in Digital Imaging and Communications in Medicine (DICOM) format and unwrapped using an exact unwrapping approach. Multi‐echo images should be combined before background field removal, and a brain mask created using a brain extraction tool with the incorporation of phase‐quality‐based masking. Background fields within the brain mask should be removed using a technique based on SHARP or PDF, and the optimization approach to dipole inversion should be employed with a sparsity‐based regularization. Susceptibility values should be measured relative to a specified reference, including the common reference region of the whole brain as a region of interest in the analysis. The minimum acquisition and processing details required when reporting QSM results are also provided. These recommendations should facilitate clinical QSM research and promote harmonized data acquisition, analysis, and reporting.

Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit.

Niacin, an important component of a balanced diet, is central to lipid metabolism. Occasionally used to treat hyperlipidemia, niacin is widely available without a prescription, making its use often unknown to treating physicians. Severe hepatotoxicity has been reported with niacin use. In the following report, we describe a case of hospitalization for acute decompensated cirrhosis with cholestatic morphology in a patient taking self-initiated large quantities of extended-release niacin. Despite medical management and support, the patient unfortunately expired on day 16 of hospitalization. Given ease of access and unclear long-term benefit in hyperlipidemia, the current case serves to raise awareness of niacin’s potential hepatotoxicity through highlighting a severe outcome. Although mode of liver injury remains unknown, the use of extended-release niacin formulations and prolonged high-dose supplementation is associated with enhanced hepatotoxicity. Careful review and counseling of commonly available supplements remains an important task of both hospital and primary care physicians.

Abstract The Infectious Diseases Society of America Training Program Directors Committee met in October 2022 and discussed an observed increase in clinical volume and acuity on infectious diseases (ID) services, and its impact on fellow education. Committee members sought to develop specific goals and strategies related to improving training program culture, preserving quality education on inpatient consult services and in the clinic, and negotiating change at the annual IDWeek Training Program Director meeting. This paper outlines a presentation of ideas brought forth at the meeting and is meant to serve as a reference document for infectious diseases training program directors seeking guidance in this area.

Purpose of review Hyponatremia and hypernatremia are commonly encountered electrolyte abnormalities that require timely and careful intervention, as they can be associated with significant morbidity and mortality. Recent findings This review article addresses the etiology, presentation, diagnosis, and management of both hyponatremia and hypernatremia, emphasizing the latest advancements and emerging trends in pediatric care. Summary A methodical approach is needed to accurately assess and treat hyponatremia and hypernatremia. Both conditions continue to rely on serum and urine testing, however newer tests such as copeptin and stimulated testing may hold promise to further refine testing in the future.

SummaryBackgroundRacial and ethnic disparities exist for hepatitis C virus (HCV) treatment and hepatocellular carcinoma (HCC) survival.AimTo evaluate the impact of HCV treatment on such disparities.MethodsIn a retrospective cohort study, we analysed 6069 patients with HCV‐related HCC (54.2% Asian, 30.1% White, 8.5% Black, and 7.3% Hispanic) from centres in the United States and Asia.ResultsThe mean age was 61, 60, 59 and 68, respectively, for White, Black, Hispanic and Asian patients. Black patients were most likely to have Barcelona Clinic Liver Cancer stage D, vascular invasion and distant metastasis (23% vs. 5%–15%, 20% vs. 10%–17% and 10% vs. 5%–7%, respectively; all p < 0.0001). Treatment rate with direct‐acting antiviral agents (DAA) was 35.9% for Asian, 34.9% for White, 30.3% for Hispanic (30.3%), and 18.7% for Black patients (p < 0.0001). Among those untreated or without sustained virologic response (SVR), 10‐year survival rates were 35.4, 27.5, 19.3 and 14.0, respectively, for Asian, Hispanic, White and Black patients (p < 0.0001). There were no statistically significant differences among those with SVR (p = 0.44). On multivariable analysis adjusted for relevant confounders, there was no statistically significant association between survival and being Hispanic (aHR: 0.68, p = 0.26) or Black (aHR: 1.18, p = 0.60) versus White. There was a significant association between being Asian American and survival (aHR: 0.24, p = 0.001; non‐U.S. Asian: aHR: 0.66, p = 0.05), and for SVR (aHR: 0.30, p < 0.0001).ConclusionDAA treatment rates were suboptimal. Racial and ethnic disparities resolved with HCV cure. Early diagnosis and improved access to HCV treatment is needed for all patients with HCV infection.

Bone morphogenetic proteins (BMPs) have been widely investigated for treating non-healing fractures. They participate in bone reconstruction by inducing osteoblast differentiation, and osteoid matrix production.1 The human recombinant protein of BMP-7 was among the first growth factors approved for clinical use. Despite achieving comparable results to autologous bone grafting, severe side effects have been associated with its use.2 Furthermore, BMP-7 was removed from the market.3 These complications are related to the high doses used (1.5-40 miligrams per surgery)2 compared to the physiological concentration of BMP in fracture healing (in the nanogram to picogram per milliliter range).4 In this study, we use transcript therapy to deliver chemically modified mRNA (cmRNA) encoding BMP-7. Compared to direct use of proteins, transcript therapy allows the sustained synthesis of proteins with native conformation and true post-translational modifications using doses comparable to the physiological ones.5 Moreover, cmRNA technology overcomes the safety and affordability limitations of standard gene therapy i.e. pDNA.6 BMP-7 cmRNA was delivered using Lipofectamine™ MessengerMAX™ to human mesenchymal stromal cells (hMSCs). We assessed protein expression and osteogenic capacity of hMSCs in monolayer culture and in a house-made, collagen hydroxyapatite scaffold. Using fluorescently-labelled cmRNA we observed an even distribution after loading complexes into the scaffold and a complete release after 3 days. For both monolayer and 3D culture, BMP-7 production peaked at 24 hours post-transfection, however cells transfected in scaffolds showed a sustained expression. BMP-7 transfected hMSCs yielded significantly higher ALP activity and Alizarin red staining at later timepoints compared to the untransfected group. Interestingly, BMP-7 cmRNA treatment triggered expression of osteogenic genes like OSX, RUNX-2 and OPN, which was also reflected in immunostainings. This work highlights the relevance of cmRNA technology that may overcome the shortcomings of protein delivery while circumventing issues of traditional pDNA-based gene therapy for bone regeneration.Acknowledgement: This work has been performed as part of the cmRNAbone project and has received funding from the European Union's Horizon 2020 research and innovation programme under the Grant Agreement No 874790.

Keyhole approaches, performed with the endoscope, microscope, or exoscope, aim to minimize tissue traumatization while maximizing surgical view. The exoscope can provide better ergonomics than the microscope without restricting the space inside of the keyhole, as when using the endoscope. However, a frequently quoted reason for intraoperative exoscope-to-microscope conversion is the absence of sufficient light. In this video, the authors present 4 patients who underwent posterior fossa keyhole surgery without intraoperative conversion. The surgical objective was achieved in all patients without associated morbidity. After adequate adaptation, the exoscope allows sufficient light in the surgical field to perform safe keyhole surgery. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23116

AbstractBackgroundAfrican Americans experience a high dementia burden yet are critically underrepresented in observational studies and clinical trials in memory and aging. Lack of adequate representation increases the likelihood that research findings may not generalize to African Americans. A deeper understanding of the barriers and facilitators that influence participation by younger and older African American adults is needed to support recruitment and retention in studies focused on early‐ and late‐onset neurodegenerative diseases.MethodAfrican American community leaders collaborated in design of an electronic survey that was distributed via social media focused on local zip codes. Survey respondents rated barriers and facilitators to research participation on a 0–3‐point Likert scale. Responses ≥2 corresponded with barriers/facilitators likely to influence participation decisions. Differences across age groups were evaluated using nonparametric Kruskal‐Wallis tests. Strategies to mitigate barriers and reinforce facilitators were further explored via community‐based focus groups.ResultSurvey data included responses from 240 African Americans (18‐44‐years, n = 76; 45‐64‐years, n = 83; ≥65‐years, n = 81). Requirement to undergo a diagnostic lumbar puncture was a substantial barrier to research participation across all age groups. Attending weekday visits (median = 2.0), including visits ≥2 hours (median 2.0), was a substantial barrier for individuals 18‐44‐years, but not older respondents (p = 0.001). Compensation for meals/transportation was beneficial across all age groups (median = 2.0; p<0.05). The option to attend visits in the local community or on weekends and access to door‐to‐door transportation were substantial facilitators for respondents <65‐years (median = 2.0) vs ≥65‐years (median = 0; p = 0.001). The option to complete some tests at home was a substantial facilitator for younger (18‐44‐years, median = 2.0) but not older respondents (≥65‐years, median = 0; p = 0.001). Focus group results supported survey findings and showed slight variations in priorities across age groups. Older participants (≥65‐years‐old) more frequently cited the longstanding effects of racism as a barrier to research participation compared to younger participants (45‐64‐years‐old; p = 0.008), who more frequently cited concerns regarding testing requirements (p = 0.034).ConclusionPerceived barriers and facilitators to research participation vary with age. Age‐specific strategies are needed to increase engagement, address disparities in recruitment, and promote retention of African American participants in studies of memory and aging across the lifespan.

AbstractBackgroundPerturbations in immune pathways are strongly associated with Alzheimer’s disease. A positive association between autoimmune diseases and frontotemporal dementia has been reported. We explored whether early onset Alzheimer’s disease (EOAD) would associate with autoimmune diseases.MethodWe compared 313 patients with EOAD from the Mayo Clinic Florida, Alzheimer’s Disease Research Center (ADRC) Registry with matched cognitively normal controls (NC) based on age (+/‐ 2 years) and gender at 1:2 ratio. NC were derived from Mayo Clinic Biobank Project, Rochester (N = 313) and the Mayo Clinic Study of Aging (N = 313). Data abstraction was performed by trained statisticians using ICD 9&10 codes corresponding to 40 specified autoimmune diseases and/or documentation of specified immunomodulatory treatment. Data was also abstracted via retrospective record review. We further reviewed clinical records from EOAD patients with neuropathologically confirmed Alzheimer’s disease patients enrolled in the ADRC (n = 10). Each autoimmune disease type was compared between cases and controls using Fisher’s exact test. All tests were two‐sided with alpha level set at 0.05 for statistical significance. Continuous variables were summarized as median (range) while categorical variables were reported as frequency (percentage). The prevalence of autoimmune disease in the general population was based off Hayter & Cook, 2012 and Roberts & Erdei, 2020. All data abstraction was done blinded to the clinical diagnosis and baseline demographics.ResultAutoimmune disease history was abstracted from 949 patient records (313 EOAD, 10 pathologically‐confirmed EOAD, 626 NCI). The median age was 57 years‐old. (EOAD range 28,65 yrs.; NC 30,66 yrs.). Autoimmune thyroiditis (p = 0.0008), ulcerative colitis (p = 0.011, psoriasis (<0.0001), rheumatoid arthritis (p = 0.0005), and Raynaud’s syndrome (p = 0.0021) were less prevalent in patients with EOAD compared to NC. Furthermore, patients with EOAD had a lower prevalence of immune mediated hematologic disorders.ConclusionPatients with EOAD have a lower prevalence of autoimmune diseases than NC. Immune activation identified in early onset AD patients may be unrelated to autoimmunity. Findings should be explored in late onset AD patients.