Faculty Bibliography

BACKGROUND/UNASSIGNED:Blood transfusion may precipitate adverse outcomes, including heart failure (HF), among patients with acute myocardial infarction (MI). This study characterizes the effects of a restrictive or liberal transfusion strategy on outcomes in patients with MI and anemia with and without baseline HF. METHODS/UNASSIGNED:In the MINT trial (Myocardial Ischemia and Transfusion), 3504 patients with MI and anemia (hemoglobin <10 g/dL) were randomized to a restrictive (hemoglobin <8 g/dL) or liberal (hemoglobin <10 g/dL) transfusion strategy. We compared the effects of transfusion strategy on outcomes among patients with and without baseline HF. The primary outcome was death or HF at 30 days. RESULTS/UNASSIGNED: CONCLUSIONS/UNASSIGNED:A liberal transfusion strategy is safe for patients with MI and anemia, including those with baseline HF. Restrictive transfusion tended to result in worse outcomes, particularly in patients with baseline HF. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02981407.

The oral mucosal calcified nodule (OMCN) is a rare soft tissue lesion with only 7 cases reported in the English literature. It typically presents in the pediatric population as an asymptomatic submucosal nodule of less than 2 cm size affecting the maxillary ridge or palate, though other sites are reported. The histopathology displays stratified squamous epithelium overlying fibrous connective tissue with embedded calcified aggregates bordered by variable numbers of multinucleated giant cells. Surgical excision is curative. In this report, we present a new case of OMCN, outline the characteristic histopathologic features and review the cases reported in the English literature.

BACKGROUND:The US Food and Drug Administration approved satralizumab for use in adult patients with aquaporin-4 immunoglobulin G-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) in 2020, but real-world data are limited. The objective of this case series is to describe the experience with satralizumab in adult patients with AQP4-IgG+ NMOSD who previously received rituximab. METHODS:Case information for patients with AQP4-IgG+ NMOSD who had received satralizumab for ≥6 months was obtained from US healthcare providers from April 1, 2022, to September 30, 2023. Patient characteristics, examination findings, diagnostic tests, treatment response and adverse events were recorded. Patients who received satralizumab after discontinuing treatment with rituximab were included in this case series. RESULTS:Twenty patients were included, and their ages ranged from 19 to 70 years. Overall, 45 % of patients self-identified as Black/African American, 40 % as White, 10 % as Asian and 5 % as multiracial. Time since confirmed NMOSD diagnosis ranged from 4 to 17 years. Median (range) duration of rituximab treatment was 50 (12-162) months. The main reasons for switching to satralizumab were intolerance (60 %) to and inadequate disease control (25 %) with rituximab. The majority of patients (70 %) received satralizumab for ≥24 months and as monotherapy (90 %). All 20 patients were free from radiographically confirmed relapses with satralizumab. Overall, patients maintained disease control with satralizumab, and adverse events primarily included asymptomatic laboratory abnormalities. Two patients permanently discontinued satralizumab due to adverse events. CONCLUSIONS:In this retrospective case series, satralizumab was effective and well tolerated in patients with NMOSD who switched due to ineffectiveness and/or poor tolerability of rituximab. These outcomes align with the long-term efficacy and safety outcomes with satralizumab in the Phase III SAkura clinical trials.

Nonlocal self-similarity within images has become an increasingly popular prior in deep-learning models. Despite their successful image restoration performance, such models remain largely uninterpretable due to their black-box construction. Our previous studies have shown that interpretable construction of a fully convolutional denoiser (CDLNet), with performance on par with state-of-the-art black-box counterparts, is achievable by unrolling a convolutional dictionary learning algorithm. In this manuscript, we seek an interpretable construction of a convolutional network with a nonlocal self-similarity prior that performs on par with black-box nonlocal models. We show that such an architecture can be effectively achieved by up-grading the

Extended reality (XR) modalities in health care are quickly evolving. There is a lack of systematically described developmental process and the "how to" execute a business-case guidance. This article formulates a systematic approach on the technical developmental steps and generation of business-case to guide the iterative development of an XR tool. An international expert group was established and several available frameworks related to entrepreneurship and business-case development were used to generate recommendations. Our ongoing experience with the development life cycle of an XR tool for cardiopulmonary resuscitation training is provided as a real-life case illustration. Market demand, value proposition, stakeholder analyses, and profitability scenarios are captured with a business model canvas. Developmental process is divided into 4 aspects: Desirability, Feasibility, Viability, and Scalability. Technical- and Investment Readiness Level models are used in defining the technical feasibility and the business viability and scalability, respectively. Best practice recommendations including examples are provided. Health care professionals, health care financers, and health care policymakers are urged to consider the provided systematic approach and recommendations prior to starting a venture with XR.

Up to half of individuals with depression do not respond to first-line treatments, possibly due to a lack of treatment interventions informed by neurobiology. A novel therapeutic approach for depression has recently emerged from translational work targeting aberrant activity of ventral tegmental area (VTA) dopamine neurons via modulation of the KCNQ voltage-gated potassium channels. In this study, individuals with major depressive disorder (MDD) with elevated anhedonia were randomized to five weeks of the KCNQ channel opener, ezogabine (up to 900 mg/day) or placebo. Participants completed functional MRI during a monetary anticipation task and resting-state at baseline and at end-of-treatment. The clinical results were reported previously. Here, we examined VTA activity during monetary anticipation and resting-state functional connectivity between the VTA and the ventromedial prefrontal cortex (mesocortical pathway) and ventral striatum (mesolimbic pathway) at baseline and end-of-treatment. Results indicated a significant drug-by-time interaction in VTA activation during anticipation (F_(1,34) = 4.36, p = 0.044), where VTA activation was reduced from pre-to-post ezogabine, compared to placebo. Mesocortical functional connectivity was also higher in depressed participants at baseline compared to a healthy control group (t₍₅₆₎ = 2.68, p = 0.01) and associated with VTA hyper-activity during task-based functional MRI at baseline (R = 0.352, p = 0.033). Mesocortical connectivity was also reduced from pre-to-post ezogabine, compared to placebo (significant drug-by-time interaction, F_(1,33) = 4.317, p = 0.046). Together this translational work is consistent with preclinical findings highlighting VTA hyper-activity in depression, and suggesting a mechanism of action for KCNQ channel openers in normalizing this hyper-activity in individuals with both depression and anhedonia.

BACKGROUND/UNASSIGNED:Whether prolonged and excessive alcohol consumption contributes to dilated cardiomyopathy (DCM) remains uncertain. This study aimed to describe the prevalence of alcohol use in patients with DCM and their first-degree relatives (FDRs) and determine if cumulative alcohol exposure associates with DCM/partial DCM or modifies the association of DCM with DCM-relevant rare variants. METHODS/UNASSIGNED:All probands had DCM; FDRs were classified as with or without DCM or partial DCM. Alcohol exposure was measured with the Alcohol Use Disorder Identification Test-Consumption questionnaire and years of drinking. Rare variants in 36 DCM genes were classified as pathogenic, likely pathogenic, or variants of uncertain significance (pathogenic, likely pathogenic, variant of uncertain significance). Generalized linear mixed models were used to assess the association of DCM/partial DCM with alcohol use among FDRs. RESULTS/UNASSIGNED:=0.55). CONCLUSIONS/UNASSIGNED:Alcohol use was frequent among probands and FDRs. This study did not provide evidence supporting an association of cumulative alcohol exposure with DCM/partial DCM or a modifying effect of alcohol use on the association of DCM with DCM-relevant rare variants. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037632.

The goal of the MRI4ALL hackathon, which took place in October 2023, was to develop a functional low-field MRI scanner in just one week and to release all created source code and resources as open-source packages. The event was attended by 52 participants from 16 institutions who assembled the scanner on the last day of the hackathon. The scanner's magnetic B₀ field with a strength of 43 mT and a target field-of-view size of 11 cm³ was created with a Halbach array made from 990 N40UH permanent magnets, held in place using 3D printed ring formers. Gradient coils were fabricated by gluing enameled copper wire onto 3D printed holders with imprinted wire patterns. A solenoid coil for RF transmission and reception was built by winding 20 turns of Litz wire around a 3D printed cylinder. A Red Pitaya FPGA prototyping board running the MaRCoS framework was used to control the scanner components, and a GPA-FHDO amplifier board was used to drive the gradients. To simplify the scanner's operation, console software with an intuitive graphical user interface was developed in Python using the PyPulseq package for sequence calculations. Furthermore, the scanner was equipped with a cooling system, as well as options for passive and active shimming. After resolving several technical issues that arose during the assembly, the scanner is now able to acquire MR images with different sequences. While not suitable for real-world clinical applications, it can be utilized for educational purposes or as a low-cost prototyping platform. Moreover, it may serve as a reference design for future MRI development projects. All source code and resources are available on the project website mri4all.org, allowing other groups to replicate the scanner. EVIDENCE LEVEL: n/a TECHNICAL EFFICACY: Stage 1.

Progressive supranuclear palsy (PSP) is a rare, debilitating neurodegenerative disorder that significantly impairs both motor and cognitive functions. Current pharmacological treatments offer only transient symptomatic relief, driving interest in the past in alternative therapeutic strategies such as deep brain stimulation. Deep brain stimulation (DBS), known for its success in treating motor symptoms of Parkinson's disease, has been explored as a possible symptomatic treatment for PSP, considering the pedunculopontine nucleus (PPN), involved in motor control and postural stability, as a promising target for deep brain stimulation in PSP. However, its complex anatomy and the clinical variability of PSP complicate the prediction and generalization of the effectiveness of DBS. The present review examines the existing studies in the literature about DBS in PSP patients. Some studies highlighted modest benefits in motor symptoms, while others reported variable outcomes and inherent risks of the procedure. Generally, patients with a parkinsonism predominant phenotype have shown some subjective or clinical improvements in gait and balance when subjected to low-frequency stimulation. While DBS of the PPN holds promise for ameliorating gait and balance of PSP, current evidence does not yet establish clear criteria for ideal candidates, nor does it provide overwhelmingly supportive results in favor of PPN-DBS in PSP patients. Without any further systematic study is not possible to define accurate candidate selection parameters and understand long-term outcomes and safety profiles.