Atrial Fibrillation in Hypertrophic Cardiomyopathy.

Atrial fibrillation (AF) is common among patients with hypertrophic cardiomyopathy (HCM) with a prevalence greater than 25%. AF in HCM is associated with a high risk of stroke and can be a marker of more advanced cardiomyopathy. Although, it frequently results in cardiac hemodynamic changes which are poorly tolerated, it can be subclinical. Thus, prompt diagnosis and adequate management of AF are essential to minimizing AF-related adverse outcomes in HCM. All HCM patients should be screened for AF regularly, and those with high-risk features should be screened more frequently preferably with extended ambulatory monitoring. Once AF is detected, oral anticoagulation should be initiated. Both general and HCM-specific modifiable risk factors should be addressed and assessment for cardiomyopathy progression should be performed. Although no randomized controlled studies have compared rate versus rhythm control in HCM, early rhythm control could be considered to prevent further LA remodeling.

Primary Spinal Malignant Melanoma Mimicking a Cervical Nerve Root Schwannoma: Case Report and Literature Review.

Primary spinal malignant melanoma (PSMM) is a rare cancer of the central nervous system (CNS), and PSMM of the spinal nerve root is even more extraordinary. PSMM of a nerve root can mimic the radiographic appearance of benign nerve sheath tumors, thus resulting in misdiagnosis until tissue diagnosis can be made. A 53-year-old African American woman presented with pain primarily involving the left aspect of her neck and shoulder for 2 years. Magnetic resonance imaging (MRI) of the cervical spine demonstrated a T1-hyperintense, T2-hypointense, homogenously enhancing, dumbbell-shaped, intradural extramedullary mass extending out through the left C2-3 foramen. A midline incision was used to perform a C2 and C3 laminectomy, and the mass was removed from the cavity. The histopathologic profile was consistent with the diagnosis of malignant melanoma. The present case report adds to the 110 cases of PSMM and the 20 cases of PSMM of the spinal nerve root in the existing body of literature. Radiographic and clinical features resemble that of the much more common schwannoma or neurofibroma requiring immunohistochemical analysis for definitive diagnosis. The optimal treatment for PSMM has not yet been defined due to its rarity and it is therefore important to report such cases in order to share our clinical experiences and provide data to other clinicians treating this uncommon disease.

Remote myocardial fibrosis predicts adverse outcome in patients with myocardial infarction on clinical cardiovascular magnetic resonance imaging.

BACKGROUND: Heart failure (HF) most commonly occurs in patients who have had a myocardial infarction (MI), but factors other than MI size may be deterministic. Fibrosis of myocardium remote from the MI is associated with adverse remodeling. We aimed to 1) investigate the association between remote myocardial fibrosis, measured using cardiovascular magnetic resonance (CMR) extracellular volume fraction (ECV), and HF and death following MI, 2) identify predictors of remote myocardial fibrosis in patients with evidence of MI and determine the relationship with infarct size. METHODS: Multicenter prospective cohort study of 1199 consecutive patients undergoing CMR with evidence of MI on late gadolinium enhancement. Median follow-up was 1133 (895-1442) days. Cox proportional hazards modeling was used to identify factors predictive of the primary outcome, a composite of first hospitalization for HF (HHF) or all-cause mortality, post-CMR. Linear regression modeling was used to identify determinants of remote ECV. RESULTS: Remote myocardial fibrosis was a strong predictor of primary outcome (χ2: 15.6, hazard ratio [HR]: 1.07 per 1% increase in ECV, 95% confidence interval [CI]: 1.04-1.11, p < 0.001) and was separately predictive of both HHF and death. The strongest predictors of remote ECV were diabetes, sex, natriuretic peptides, and body mass index, but, despite extensive phenotyping, the adjusted model R2 was only 0.283. The relationship between infarct size and remote fibrosis was very weak. CONCLUSION: Myocardial fibrosis, measured using CMR ECV, is a strong predictor of HHF and death in patients with evidence of MI. The mechanisms underlying remote myocardial fibrosis formation post-MI remain poorly understood, but factors other than infarct size appear to be important.

The UTHealth Houston Adult Cardiovascular Genomics Certificate Program: Efficacy and Impact on Healthcare Professionals.

Background: The demand for genetic services has outpaced the availability of resources, challenging clinicians untrained in genetic integration into clinical decision-making. The UTHealth Adult Cardiovascular Genomics Certificate (CGC) program trains non-genetic healthcare professionals to recognize, assess, and refer patients with heritable cardiovascular diseases. This asynchronous online course includes 24 modules in three tiers of increasing complexity, using realistic clinical scenarios, interactive dialogues, quizzes, and tests to reinforce learning. We hypothesized that the CGC will increase genomic competencies in this underserved audience and encourage applying genomic concepts in clinical practice. Methods: Required course evaluations include pre- and post-assessments, knowledge checks in each module, and surveys for module-specific feedback. After 6 months, longitudinal feedback surveys gathered data on the long-term impact of the course on clinical practice and conducted focused interviews with learners. Results: The CGC was accredited in September 2022. Principal learners were nurses (24%), nurse practitioners (21%), physicians (16%), and physician assistants. Scores of 283 learners in paired pre- and post-assessments increased specific skills related to recognizing heritable diseases, understanding inheritance patterns, and interpreting genetic tests. Interviews highlighted the CGC's modular structure and linked resources as key strengths. Learners endorsed confidence to use genetic information in clinical practice, such as discussing genetic concepts and risks with patients and referring patients for genetic testing. Learners were highly likely to recommend the CGC to colleagues, citing its role in enhancing heritable disease awareness. Conclusions: The CGC program effectively empowers non-genetic clinicians to master genomic competencies, fostering collaboration to prevent deaths from heritable cardiovascular diseases, and potentially transforming healthcare education and clinical practice.

AI analysis of super-resolution microscopy: Biological discovery in the absence of ground truth.

Super-resolution microscopy, or nanoscopy, enables the use of fluorescent-based molecular localization tools to study molecular structure at the nanoscale level in the intact cell, bridging the mesoscale gap to classical structural biology methodologies. Analysis of super-resolution data by artificial intelligence (AI), such as machine learning, offers tremendous potential for the discovery of new biology, that, by definition, is not known and lacks ground truth. Herein, we describe the application of weakly supervised paradigms to super-resolution microscopy and its potential to enable the accelerated exploration of the nanoscale architecture of subcellular macromolecules and organelles.

Empowering people living with HIV (PLHIV): unveiling care gaps and identifying opportunities for improving care for PLHIV in Singapore and Hong Kong.

INTRODUCTION: This study explored the behaviours of people living with HIV in Singapore and Hong Kong in terms of achieving and maintaining their physical and psychological wellbeing in relation to HIV, to identify the challenges and support needed in HIV care. METHODS: This qualitative study involved 90-minute interviews among Singapore and Hong Kong people living with HIV aged ≥18 years to explore health-related quality of life perceptions and gaps in patient empowerment in HIV care during February-May 2022. The COM-B (C: Capability; O: Opportunity; M: Motivation; B: Behaviour) framework was used during data analysis to identify behaviour facilitators and barriers for people living with HIV to achieve and maintain their wellbeing. Detailed accounts of respondents' experience of living with and managing HIV, that is what worked well, unmet needs and perceived significance of wellbeing indicators, were analysed qualitatively via a combination of inductive content and deductive frameworks. RESULTS: A total of 30 and 28 respondents were recruited from Singapore (SG) and Hong Kong (HK), respectively. Most respondents were aged 20-49 years (SG: 83.3%; HK: 64.3%), males (SG: 96.7%; HK: 92.9%), men who have sex with men (SG: 93.3%; HK: 71.4%), had university or higher education (SG: 73.3%; HK: 50.0%) and were fully employed (SG: 73.3%; HK: 57.1%). In both Singapore and Hong Kong, physical health was considered a key focus of overall wellbeing, albeit attention to long-term health associated with cardiovascular and renal health was less salient. The impact of symptoms, side effects of treatment, mood and sleep were among the top wellbeing indicators of importance. Respondents felt that insufficient information was provided by physicians, citing consultation time and resource constraints impeding further expression of concerns to their physicians during consultation. Respondents prioritized functional wellness and delegated psychosocial health to supportive care professionals, patient groups, families and/or friends. CONCLUSIONS: There is a need in Singapore and Hong Kong to empower people living with HIV to establish better communications with their physicians and be more involved in their treatment journey and equally prioritize their psychosocial wellbeing.

Efficacy and Safety of Aficamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4.

BACKGROUND: This open-label phase 2 trial evaluated the safety and efficacy of aficamten in patients with nonobstructive hypertrophic cardiomyopathy (nHCM). METHODS: Patients with symptomatic nHCM (left ventricular outflow tract obstruction gradient ≤ 30 mmHg, left ventricular ejection fraction [LVEF] ≥ 60%, N-terminal pro-B-type natriuretic peptide [NT-proBNP] > 300 pg/mL) received aficamten 5-15 mg once daily (doses adjusted according to echocardiographic LVEF) for 10 weeks. RESULTS: We enrolled 41 patients (mean ± SD age 56 ± 16 years; 59% female). At Week 10, 22 (55%) patients experienced an improvement of ≥ 1 New York Heart Association class; 11 (29%) became asymptomatic. Clinically relevant improvements in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores occurred in 22 (55%) patients. Symptom relief was paralleled by reductions in NT-proBNP levels (56%; P < 0.001) and high-sensitivity cardiac troponin I (22%; P < 0.005). Modest reductions in LVEF (mean ± SD) of -5.4% ± 10 to 64.6% ± 9.1 were observed. Three (8%) patients had asymptomatic reduction in LVEF < 50% (range: 41%-48%), all returning to normal after 2 weeks of washout. One patient with prior history of aborted sudden cardiac death experienced a fatal arrhythmia during the study. CONCLUSIONS: Aficamten administration for symptomatic nHCM was generally safe and was associated with improvements in heart failure symptoms and cardiac biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04219826.

Functional outcomes in MRI-guided laser interstitial therapy for temporal lobe epilepsy: a systematic review and meta-analysis.

OBJECTIVE: The use of MRI-guided laser interstitial thermal therapy (MRgLITT) has emerged as a promising treatment option for patients with drug-resistant temporal lobe epilepsy (TLE). Although the minimally invasive approach holds promise as an effective treatment for achieving seizure freedom, a comprehensive review of its impact on functional outcomes is still warranted. To address this need, this review aims to summarize data pertaining to the functional and neurocognitive outcomes following MRgLITT for TLE. METHODS: Four primary electronic databases were screened following PRISMA guidelines by two independent reviewers. All functional data related to cognitive, behavioral, and emotional outcomes were gathered and analyzed as well as the neuropsychological tests issued to assess pre- and postoperative outcomes. The functional outcomes assessed were grouped into the 5 most common categories: verbal cognition, visual cognition, cognitive emotion, visual deficits, and other higher-order cognitive functioning. RESULTS: A total of 4184 studies were screened and ultimately 408 patients from 14 studies were included for analysis. Changes in functional areas were assessed by comparing pre- and postoperative scores across a comprehensive set of 31 different functional and cognitive assessments, and were tabulated as the percentage of patients whose status improved, declined, or was maintained, where possible. In verbal (n = 112) and visual (n = 42) cognition, the rates of patients experiencing a decline were 20.4% and 13.5%, respectively, and the rates of improvement were 24.9% and 16.7%, respectively. Other functional outcomes assessed, including cognitive emotion (n = 150), visual deficits (n = 325), and higher-order cognitive processes like attention/processing (n = 19), motor cognition (n = 18), and general executive function (n = 4), exhibited varying rates of decline, ranging from 10.5% to 25%. CONCLUSIONS: MRgLITT is an effective and minimally invasive surgical alternative treatment for TLE, but there is an observable impact on patient functioning and cognitive status. This review demonstrates the need for standardized methods that can accurately capture and quantify the associated risk of MRgLITT to optimize its effect on patient quality of life moving forward.

A computational study on the effects of fast-rising voltage on ionization fronts initiated in sub-mm air and CO[Formula: see text] gaps.

Gas discharge and breakdown phenomena have become increasingly important for the development of an ever-growing number of applications. The need for compact and miniaturized systems within power, pulsed power, semiconductor, and power electronic industries has led to the imposing of significant operating electric field stresses on components, even within applications with low operating voltages. Consequently, the interest in gas discharge processes in sub-millimeter and microscale gaps has grown, as the understanding of their initiation and propagation is critical to the further optimization of these technologies. In this work, a computational study of primary ionization fronts has been conducted, which systematically investigated the role of voltage rate-of-rise in point-plane and point-point electrode geometries with an inter-electrode gap maintained at 250 [Formula: see text]m and a needle radius of 80 [Formula: see text]m. Using the hydrodynamic approach with the local mean energy approximation, along with simplified plasma chemistry, simulations have been performed under positive and negative ramp voltages, rising at 50, 25, 16.67, 12.5, and 10 kV/ns in synthetic air and in pure CO[Formula: see text]. Results on the developed electric field, electron densities, and propagation velocities are presented and discussed. Effects on the cathode sheath thickness scaling with voltage rate-of-rise have been additionally analyzed, the mechanisms behind these effects and their potential impacts are discussed. The work conducted in this study contributes towards an increased understanding of the gas discharge process, under fast-transients and nonuniform electric fields, with relevance to microelectromechanical, power, and pulsed power system design.

Caveolin-1 promotes mitochondrial health and limits mitochondrial ROS through ROCK/AMPK regulation of basal mitophagic flux.

Caveolin-1 (CAV1), the main structural component of caveolae, is phosphorylated at tyrosine-14 (pCAV1), regulates signal transduction, mechanotransduction, and mitochondrial function, and plays contrasting roles in cancer progression. We report that CRISPR/Cas9 knockout (KO) of CAV1 increases mitochondrial oxidative phosphorylation, increases mitochondrial potential, and reduces ROS in MDA-MB-231 triple-negative breast cancer cells. Supporting a role for pCAV1, these effects are reversed upon expression of CAV1 phosphomimetic CAV1 Y14D but not non-phosphorylatable CAV1 Y14F. pCAV1 is a known effector of Rho-associated kinase (ROCK) signaling and ROCK1/2 signaling mediates CAV1 promotion of increased mitochondrial potential and decreased ROS production in MDA-MB-231 cells. CAV1/ROCK control of mitochondrial potential and ROS is caveolae-independent as similar results were observed in PC3 prostate cancer cells lacking caveolae. Increased mitochondrial health and reduced ROS in CAV1 KO MDA-MB-231 cells were reversed by knockdown of the autophagy protein ATG5, mitophagy regulator PINK1 or the mitochondrial fission protein Drp1 and therefore due to mitophagy. Use of the mitoKeima mitophagy probe confirmed that CAV1 signaling through ROCK inhibited basal mitophagic flux. Activation of AMPK, a major mitochondrial homeostasis protein inhibited by ROCK, is inhibited by CAV1-ROCK signaling and mediates the increased mitochondrial potential, decreased ROS, and decreased basal mitophagy flux observed in wild-type MDA-MB-231 cells. CAV1 regulation of mitochondrial health and ROS in cancer cells therefore occurs via ROCK-dependent inhibition of AMPK. This study therefore links pCAV1 signaling activity at the plasma membrane with its regulation of mitochondrial activity and cancer cell metabolism through control of mitophagy.

Vimentin-mediated myosin 10 aggregation at tips of cell extensions drives MT1-MMP-dependent collagen degradation in colorectal cancer.

Colorectal cancer (CRC) is a high prevalence adenocarcinoma with progressive increases in metastasis-related mortality, but the mechanisms governing the extracellular matrix (ECM) degradation important for metastasis in CRC are not well-defined. We investigated a functional relationship between vimentin (Vim) and myosin 10 (Myo10), and whether this relationship is associated with cancer progression. We tested the hypothesis that Vim regulates the aggregation of Myo10 at the tips of cell extensions, which increases membrane-type 1 matrix metalloproteinase (MT1-MMP)-associated local collagen proteolysis and ECM degradation. Analysis of CRC samples revealed colocalization of Vim with Myo10 and MT1-MMP in cell extensions adjacent to sites of collagen degradation, suggesting an association with local cell invasion. We analyzed cultured CRC cells and fibroblasts and found that Vim accelerates aggregation of Myo10 at cell tips, which increases the cell extension rate. Vim stabilizes the interaction of Myo10 with MT1-MMP, which in turn increases collagenolysis. Vim depletion reduced the aggregation of Myo10 at the cell extension tips and MT1-MMP-dependent collagenolysis. We propose that Vim interacts with Myo10, which in turn associates with MT1-MMP to facilitate the transport of these molecules to the termini of cell extensions and there enhance cancer invasion of soft connective tissues.

Consultation-Liaison Case Conference: A Case of Factitious Disorder Imposed on Self.

We present the case of a young woman with an extensive medical history that most notably includes over 60 emergency-room visits for unfounded respiratory distress that often prompted intubations. Each presentation displays elements of deceitfulness or inappropriate demands that align with factitious disorder imposed on self. Top experts in the Consultation-Liaison field provide guidance for this commonly encountered clinical case based on their experience and review of available literature. Key teaching topics include a review of risk factors for development of deceptive syndromes, distinguishing factitious disorder from malingering and conversion disorder, and the role of a consulting psychiatrist in such cases. Patients with factitious disorder often show signs of pathologic lying, obstinance, and erratic behavior. Such attributes frequently arouse negative countertransference in providers, causing frustration and dread with continuing care, rendering psychiatric involvement. We address the unique challenges in managing factitious disorder and how to effectively collaborate with an interdisciplinary inpatient team with these cases.

Nonequilibrium sensing of volatile compounds using active and passive analyte delivery.

Although sensor technologies have allowed us to outperform the human senses of sight, hearing, and touch, the development of artificial noses is significantly behind their biological counterparts. This largely stems from the sophistication of natural olfaction, which relies on both fluid dynamics within the nasal anatomy and the response patterns of hundreds to thousands of unique molecular-scale receptors. We designed a sensing approach to identify volatiles inspired by the fluid dynamics of the nose, allowing us to extract information from a single sensor (here, the reflectance spectra from a mesoporous one-dimensional photonic crystal) rather than relying on a large sensor array. By accentuating differences in the nonequilibrium mass-transport dynamics of vapors and training a machine learning algorithm on the sensor output, we clearly identified polar and nonpolar volatile compounds, determined the mixing ratios of binary mixtures, and accurately predicted the boiling point, flash point, vapor pressure, and viscosity of a number of volatile liquids, including several that had not been used for training the model. We further implemented a bioinspired active sniffing approach, in which the analyte delivery was performed in well-controlled 'inhale-exhale' sequences, enabling an additional modality of differentiation and reducing the duration of data collection and analysis to seconds. Our results outline a strategy to build accurate and rapid artificial noses for volatile compounds that can provide useful information such as the composition and physical properties of chemicals, and can be applied in a variety of fields, including disease diagnosis, hazardous waste management, and healthy building monitoring.

Transient photocurrents in a subthreshold evidence accumulator accelerate perceptual decisions.

Perceptual decisions are complete when a continuously updated score of sensory evidence reaches a threshold. In Drosophila, αß core Kenyon cells (αßc KCs) of the mushroom bodies integrate odor-evoked synaptic inputs to spike threshold at rates that parallel the speed of olfactory choices. Here we perform a causal test of the idea that the biophysical process of synaptic integration underlies the psychophysical process of bounded evidence accumulation in this system. Injections of single brief, EPSP-like depolarizations into the dendrites of αßc KCs during odor discrimination, using closed-loop control of a targeted opsin, accelerate decision times at a marginal cost of accuracy. Model comparisons favor a mechanism of temporal integration over extrema detection and suggest that the optogenetically evoked quanta are added to a growing total of sensory evidence, effectively lowering the decision bound. The subthreshold voltage dynamics of αßc KCs thus form an accumulator memory for sequential samples of information.

Dynamic modelling of chronotype and hypo/manic and depressive symptoms in young people with emerging mental disorders.

There is significant interest in the possible influence of chronotype on clinical states in young people with emerging mental disorders. We apply a dynamic approach (bivariate latent change score modelling) to examine the possible prospective influence of chronotype on depressive and hypo/manic symptoms in a youth cohort with predominantly depressive, bipolar, and psychotic disorders (N = 118; 14-30-years), who completed a baseline and follow-up assessment of these constructs (mean interval = 1.8-years). Our primary hypotheses were that greater baseline eveningness would predict increases in depressive but not hypo/manic symptoms. We found moderate to strong autoregressive effects for chronotype (ß = -0.447 to -0.448, p < 0.001), depressive (ß = -0.650, p < 0.001) and hypo/manic symptoms (ß = -0.819, p < 0.001). Against our predictions, baseline chronotypes did not predict change in depressive (ß = -0.016, p = 0.810) or hypo/manic symptoms (ß = 0.077, p = 0.104). Similarly, the change in chronotype did not correlate with the change in depressive symptoms (ß = -0.096, p = 0.295) nor did the change in chronotype and the change in hypo/manic symptoms (ß = -0.166, p = 0.070). These data suggest that chronotypes may have low utility for predicting future hypo/manic and depressive symptoms in the short term, or that more frequent assessments over longer periods are needed to observe these associations. Future studies should test whether other circadian phenotypes (e.g. sleep-wake variability) are better indicators of illness course.

Cardiovascular magnetic resonance for evaluation of cardiac involvement in COVID-19: recommendations by the Society for Cardiovascular Magnetic Resonance.

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic that has affected nearly 600 million people to date across the world. While COVID-19 is primarily a respiratory illness, cardiac injury is also known to occur. Cardiovascular magnetic resonance (CMR) imaging is uniquely capable of characterizing myocardial tissue properties in-vivo, enabling insights into the pattern and degree of cardiac injury. The reported prevalence of myocardial involvement identified by CMR in the context of COVID-19 infection among previously hospitalized patients ranges from 26 to 60%. Variations in the reported prevalence of myocardial involvement may result from differing patient populations (e.g. differences in severity of illness) and the varying intervals between acute infection and CMR evaluation. Standardized methodologies in image acquisition, analysis, interpretation, and reporting of CMR abnormalities across would likely improve concordance between studies. This consensus document by the Society for Cardiovascular Magnetic Resonance (SCMR) provides recommendations on CMR imaging and reporting metrics towards the goal of improved standardization and uniform data acquisition and analytic approaches when performing CMR in patients with COVID-19 infection.

Diffuse myocardial fibrosis associates with incident ventricular arrhythmia in implantable cardioverter defibrillator recipients.

Background: Diffuse myocardial fibrosis (DMF) quantified by extracellular volume (ECV) may represent a vulnerable phenotype and associate with life threatening ventricular arrhythmias more than focal myocardial fibrosis. This principle remains important because 1) risk stratification for implantable cardioverter defibrillators (ICD) remains challenging, and 2) DMF may respond to current or emerging medical therapies (reversible substrate). Objectives: To evaluate the association between quantified by ECV in myocardium without focal fibrosis by late gadolinium enhancement (LGE) with time from ICD implantation to 1) appropriate shock, or 2) shock or anti-tachycardia pacing. Methods: Among patients referred for cardiovascular magnetic resonance (CMR) without congenital disease, hypertrophic cardiomyopathy, or amyloidosis who received ICDs (n=215), we used Cox regression to associate ECV with incident ICD therapy. Results: After a median of 2.9 (IQR 1.5-4.2) years, 25 surviving patients experienced ICD shock and 44 experienced shock or anti-tachycardia pacing. ECV ranged from 20.2% to 39.4%. No patient with ECV<25% experienced an ICD shock. ECV associated with both endpoints, e.g., hazard ratio 2.17 (95%CI 1.17-4.00) for every 5% increase in ECV, p=0.014 in a stepwise model for ICD shock adjusting for ICD indication, age, smoking, atrial fibrillation, and myocardial infarction, whereas focal fibrosis by LGE and global longitudinal strain (GLS) did not. Conclusions: DMF measured by ECV associates with ventricular arrhythmias requiring ICD therapy in a dose-response fashion, even adjusting for potential confounding variables, focal fibrosis by LGE, and GLS. ECV-based risk stratification and DMF representing a therapeutic target to prevent ventricular arrhythmia warrant further investigation.

Myocardial Injury on CMR in Patients With COVID-19 and Suspected Cardiac Involvement.

BACKGROUND: Myocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood. OBJECTIVES: The purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR). METHODS: This retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction-confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR. RESULTS: In this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic: 13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95% CI: 1.17-3.40, P = 0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95% CI: 1.12-3.23; P = 0.02), natriuretic peptide elevation (OR: 2.99; 95% CI: 1.60-5.58; P = 0.0006), and troponin elevation (OR: 4.21; 95% CI: 2.41-7.36; P < 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95% CI: 1.04-9.49; P = 0.04), abnormal ECG (OR: 4.06; 95% CI: 1.10-14.92; P = 0.04), known coronary disease (OR: 33.30; 95% CI: 4.04-274.53; P = 0.001), hospitalization (OR: 4.98; 95% CI: 1.55-16.05; P = 0.007), natriuretic peptide elevation (OR: 4.19; 95% CI: 1.30-13.51; P = 0.02), and troponin elevation (OR: 25.27; 95% CI: 5.55-115.03; P < 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95% CI: 1.76-14.05; P = 0.003). CONCLUSIONS: In this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present.

Expanded Potential Stem Cells from Human Embryos Have an Open Chromatin Configuration with Enhanced Trophoblast Differentiation Ability.

Human expanded potential stem cells (hEPSC) have been derived from human embryonic stem cells and induced pluripotent stem cells. Here direct derivation of hEPSC from human pre-implantation embryos is reported. Like the reported hEPSC, the embryo-derived hEPSC (hEPSC-em) exhibit a transcriptome similar to morula, comparable differentiation potency, and high genome editing efficiency. Interestingly, the hEPSC-em show a unique H3 lysine-4 trimethylation (H3K4me3) open chromatin conformation; they possess a higher proportion of H3K4me3 bound broad domain (>5 kb) than the reported hEPSC, naive, and primed embryonic stem cells. The open conformation is associated with enhanced trophoblast differentiation potency with increased trophoblast gene expression upon induction of differentiation and success in derivation of trophoblast stem cells with bona fide characteristics. Hippo signaling is specifically enriched in the H3K4me3 broad domains of the hEPSC-. Knockout of the Hippo signaling gene, YAP1 abolishes the ability of the embryo-derived EPSC to form trophoblast stem cells.