Strategies for Identifying and Recruiting Women at High Risk for Breast Cancer for Research Outside of Clinical Settings: Observational Study.

BACKGROUND: Research is needed to understand and address barriers to risk management for women at high (≥20% lifetime) risk for breast cancer, but recruiting this population for research studies is challenging. OBJECTIVE: This paper compares a variety of recruitment strategies used for a cross-sectional, observational study of high-risk women. METHODS: Eligible participants were assigned female at birth, aged 25-85 years, English-speaking, living in the United States, and at high risk for breast cancer as defined by the American College of Radiology. Individuals were excluded if they had a personal history of breast cancer, prior bilateral mastectomy, medical contraindications for magnetic resonance imaging, or were not up-to-date on screening mammography per American College of Radiology guidelines. Participants were recruited from August 2020 to January 2021 using the following mechanisms: targeted Facebook advertisements, Twitter posts, ResearchMatch (a web-based research recruitment database), community partner promotions, paper flyers, and community outreach events. Interested individuals were directed to a secure website with eligibility screening questions. Participants self-reported method of recruitment during the eligibility screening. For each recruitment strategy, we calculated the rate of eligible respondents and completed surveys, costs per eligible participant, and participant demographics. RESULTS: We received 1566 unique responses to the eligibility screener. Participants most often reported recruitment via Facebook advertisements (724/1566, 46%) and ResearchMatch (646/1566, 41%). Community partner promotions resulted in the highest proportion of eligible respondents (24/46, 52%), while ResearchMatch had the lowest proportion of eligible respondents (73/646, 11%). Word of mouth was the most cost-effective recruitment strategy (US $4.66 per completed survey response) and paper flyers were the least cost-effective (US $1448.13 per completed survey response). The demographic characteristics of eligible respondents varied by recruitment strategy: Twitter posts and community outreach events resulted in the highest proportion of Hispanic or Latina women (1/4, 25% and 2/6, 33%, respectively), and community partner promotions resulted in the highest proportion of non-Hispanic Black women (4/24, 17%). CONCLUSIONS: Although recruitment strategies varied in their yield of study participants, results overall support the feasibility of identifying and recruiting women at high risk for breast cancer outside of clinical settings. Researchers must balance the associated costs and participant yield of various recruitment strategies in planning future studies focused on high-risk women.

Hematopoietic Cell Transplantation for DOCK8 Deficiency: Results from a Prospective Clinical Trial.

BACKGROUND: Dedicator of cytokinesis 8 (DOCK8) deficiency is a primary immunodeficiency in which allogeneic hematopoietic cell transplantation (HCT) represents the only known cure. We tested the ability of a busulfan-based regimen to achieve reliable engraftment and high levels of donor chimerism with acceptable toxicity in a prospective clinical trial in DOCK8 deficiency. OBJECTIVE: To both evaluate the ability of HCT to reverse the clinical phenotype and to correct the immunologic abnormalities by 1-year post-HCT. METHODS: We conducted a prospective HCT trial for recipients with DOCK8 deficiency. Subjects were recruited from October 5th, 2010, to December 30th, 2022. Donor sources included fully matched related (MRD) and unrelated (MUD) and haploidentical (Haplo) donors. The reduced toxicity, myeloablative conditioning regimen contained no serotherapy. Graft-versus-host disease (GVHD) prophylaxis included either a calcineurin inhibitor (CNI) with methotrexate (MTX) or post-HCT cyclophosphamide (PT/Cy) followed by tacrolimus and mycophenolate mofetil (MMF). The trial was later amended to study PT/Cy in all patients. (ClinicalTrials.gov NCT01176006). RESULTS: Thirty-six subjects, children, and adults (median age 16.4 years) underwent HCT for DOCK8 deficiency. Most patients, 33 of 36 (92%), achieved full (≥98%) donor chimerism in whole blood as early as day +30. With a median potential follow-up of 7.4 years, 29 (80.6%) were alive with no evidence of new DOCK8 deficiency-related complications. PT/Cy was effective in reducing the risk of acute GVHD in patients who had received MUDs and Haplo transplants, but it was associated with transient delays in immune-reconstitution and hemorrhagic cystitis (HC). CONCLUSION: A busulfan-based HCT regimen using PT/Cy for GVHD prophylaxis and a broad range of donor types and hematopoietic cell sources were well-tolerated, leading to the reversal of the clinical immunophenotype.

Accelerated myocardial fibrosis in young to middle-aged patients with hypertrophic cardiomyopathy.

BACKGROUND: The extent of late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) in patients with hypertrophic cardiomyopathy (HCM) is associated with an increased risk of sudden cardiac death events. However, the clinical significance of age-specific longitudinal changes in LGE is not well characterized in HCM. We sought to assess whether the risk of LGE progression diverges between young to middle-aged (ages 20-59 years) and older (≥ 60) adults with HCM. METHODS: A total of 102 HCM patients (age <60 years; n=75, age ≥60 years; n=27) undergoing serial CMR studies from two tertiary medical centers were evaluated. The median time interval between initial and follow-up CMR scans was 3.7 years. LGE was semiautomatically quantified by measuring regions with signal intensity >6 SD above the nulled remote myocardium and manually adjusting a grayscale threshold. RESULTS: LGE was identified at baseline in 61 of the 102 HCM patients (60%), occupying 4.8 ± 3.9% of the left ventricular (LV) mass. At the end of the follow-up period, 53 of the 61 patients (87%) demonstrated an increase in the extent of LGE to 7.7 ± 5.4%, and 8 patients had no change. In 5 patients (5%), LGE increased to extensive with >15% of the LV mass. The rate of LGE progression was 0.7 ± 1.0%/year, including 21 patients (21%) with particularly accelerated progression of ≥1%/year. The risk of LGE progression ≥1%/year was significantly higher in patients <60 years than those ≥ 60 years (25% vs. 7%, p=0.03). The odds of LGE progression ≥1%/year was almost 4 times greater for patients <60 years compared with those ≥ 60 years (odds ratio, 4.2; 95%CI, 1.1-27.9). Age <60 years and LGE extent ≥ 10% were significant baseline predictors for future LGE progression ≥1%/year, even after adjustment for other potential risk factors. CONCLUSION: In HCM, progressive fibrosis occurs more frequently in young to middle-aged patients, underscoring the importance of repeating CMR to re-evaluate for potential LGE progression in this age group.

Barriers and facilitators to breast cancer screening among high-risk women: a qualitative study.

PURPOSE: Women with greater than 20-25% lifetime breast cancer risk are recommended to have breast cancer screening with annual mammogram and supplemental breast MRI. However, few women follow these screening recommendations. The objective of this study was to identify barriers and facilitators of screening among women at high risk for breast cancer, guided by the Health Services Utilization Model (HSUM). METHODS: Unaffected high-risk women (N=63) completed semi-structured qualitative interviews exploring their experiences with breast cancer screening. Interviews were audio recorded, transcribed verbatim, and analyzed using a combined deductive and inductive approach. RESULTS: Most participants (84%) had received a screening mammogram; fewer (33%) had received a screening breast MRI. Only 14% had received neither screening. In line with the HSUM, qualitative analysis identified predisposing factors, enabling factors, and need factors associated with receipt of breast cancer screening. Enabling factors - including financial burden, logistic barriers, social support, and care coordination - were most frequently discussed. Predisposing factors included knowledge, health beliefs, and self-advocacy. Need factors included healthcare provider recommendation, family history of breast cancer, and personal medical history. Although HSUM themes were consistent for both mammography and breast MRI, participants did highlight several important differences in barriers and facilitators between the two screening modalities. CONCLUSION: Barriers and enabling factors associated with supplemental screening for high-risk women represent possible intervention targets. Future research is needed to develop and test multilevel interventions targeting these factors, with the ultimate goal of increasing access to supplemental screening for high-risk women.

Mucor germinans, a novel dimorphic species resembling Paracoccidioides in a clinical sample: questions on ecological strategy.

Dimorphism is known among the etiologic agents of endemic mycoses as well as in filamentous Mucorales. Under appropriate thermal conditions, mononuclear yeast forms alternate with multi-nucleate hyphae. Here, we describe a dimorphic mucoralean fungus obtained from the sputum of a patient with Burkitt lymphoma and ongoing graft-versus-host reactions. The fungus is described as Mucor germinans sp. nov. Laboratory studies were performed to simulate temperature-dependent dimorphism, with two environmental strains Mucor circinelloides and Mucor kunryangriensis as controls. Both strains could be induced to form multinucleate arthrospores and subsequent yeast-like cells in vitro. Multilateral yeast cells emerge in all three Mucor species at elevated temperatures. This morphological transformation appears to occur at body temperature since the yeast-like cells were observed in the lungs of our immunocompromised patient. The microscopic appearance of the yeast-like cells in the clinical samples is easily confused with that of Paracoccidioides. The ecological role of yeast forms in Mucorales is discussed.IMPORTANCEMucormycosis is a devastating disease with high morbidity and mortality in susceptible patients. Accurate diagnosis is required for timely clinical management since antifungal susceptibility differs between species. Irregular hyphal elements are usually taken as the hallmark of mucormycosis, but here, we show that some species may also produce yeast-like cells, potentially being mistaken for Candida or Paracoccidioides. We demonstrate that the dimorphic transition is common in Mucor species and can be driven by many factors. The multi-nucleate yeast-like cells provide an effective parameter to distinguish mucoralean infections from similar yeast-like species in clinical samples.

Opportunistic Infections, Mortality Risk, and Prevention Strategies in Patients With Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic (VEXAS) Syndrome.

Background: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a genetic disorder characterized by bone marrow failure and systemic inflammation, putting patients at risk for infections. This study comprehensively examines the prevalence of opportunistic infections in patients with VEXAS, evaluating their impact on clinical outcomes and potential preventive measures. Methods: Patients with confirmed VEXAS were included. Survival analysis and logistic regression were used to identify associations between opportunistic infections and mortality. Infection rates (IRs) for Pneumocystis jirovecii pneumonia (PJP) and alphaherpesviruses were calculated over a prospective 8-month observation period in relationship to prophylaxis. Results: Of 94 patients with VEXAS, 6% developed PJP; 15% had alphaherpesvirus reactivation, with varicella zoster virus (VZV) being the most common herpesvirus; and 10% contracted a nontuberculous mycobacterial (NTM) infection. Risk of death was significantly increased per month following a diagnosis of PJP (hazard ratio [HR], 72.41 [95% confidence interval {CI}, 13.67-533.70]) or NTM (HR, 29.09 [95% CI, 9.51-88.79]). Increased odds for death were also observed in patients with a history of herpes simplex virus (HSV) reactivation (odds ratio [OR], 12.10 [95% CI, 1.29-114.80]) but not in patients with VZV (OR, 0.89 [95% CI, .30-2.59]). Prophylaxis for PJP (IR, 0.001 vs 0 per person-day, P < .01) and VZV (IR, 0.006 vs 0 per person-day, P = .04) markedly decreased infection rates with a number needed to treat of 4 and 7, respectively. Conclusions: Opportunistic infections are common in patients with VEXAS. Patients who develop PJP, HSV, or NTM are at increased risk for death. Prophylaxis against PJP and VZV is highly effective.

Sustainability of a Pediatric Neurointensive Care Unit Model Within a Mixed Pediatric Intensive Care Unit and Its Effect on Nursing Sentiment.

ABSTRACT: BACKGROUND: Pediatric neurocritical care (PNCC) and pediatric neurointensive care units (neuro-PICU) are growing fields. Although some institutions have established independent neuro-PICUs meeting most Neurocritical Care Society (NCS) standards for neurocritical care units, many centers lack the resources to do so. We describe an alternative neuro-PICU model as a designated unit within a mixed pediatric intensive care unit (PICU) and its effects on nursing sentiment. METHODS: We established a 6-bed neuro-PICU within a 36-bed noncardiac PICU. Charge nurses were tasked with admitting PNCC patients into these beds. For nursing expertise, we used a core group of 12 PNCC specialty nurses and instituted PNCC nursing education to PICU nurses. We observed the number of PNCC patients admitted to neuro-PICU beds and surveyed charge nurses to identify barriers to assigning patients. We surveyed PICU nursing staff to explore sentiment regarding PNCC before and after establishing the neuro-PICU. Nursing criteria were compared with NCS standards. RESULTS: In the 40-month period, our PICU saw 2060 PNCC admissions. Overall, occupied neuro-PICU beds housed PNCC patients 74.1% of the time. The biggest barriers to patient placement were too many competing placement requests, not enough neuro-PICU beds when specialty census was high, and difficulty assigning one nurse to two PNCC patients. In surveys after establishing the neuro-PICU, compared to before, experienced nurses reported being more interested in obtaining Emergency Neurological Life Support certification (94.2% vs 80.6%, P = .0495), and inexperienced nurses reported being more familiar with PNCC clinical pathways (53.5% vs 31.7%, P = .0263). Most NCS criteria related to nursing organization were met. CONCLUSIONS: Focused neuro-PICUs should be developed to complement advances in the field of PNCC. Alternative neuro-PICU models are possible and can increase nursing interest in further education and awareness of clinical pathways, but barriers exist that require institutional commitment to nursing development to sustain the delivery of specialized care to this population.

Accelerating the design of lattice structures using machine learning.

Lattices remain an attractive class of structures due to their design versatility; however, rapidly designing lattice structures with tailored or optimal mechanical properties remains a significant challenge. With each added design variable, the design space quickly becomes intractable. To address this challenge, research efforts have sought to combine computational approaches with machine learning (ML)-based approaches to reduce the computational cost of the design process and accelerate mechanical design. While these efforts have made substantial progress, significant challenges remain in (1) building and interpreting the ML-based surrogate models and (2) iteratively and efficiently curating training datasets for optimization tasks. Here, we address the first challenge by combining ML-based surrogate modeling and Shapley additive explanation (SHAP) analysis to interpret the impact of each design variable. We find that our ML-based surrogate models achieve excellent prediction capabilities (R2 > 0.95) and SHAP values aid in uncovering design variables influencing performance. We address the second challenge by utilizing active learning-based methods, such as Bayesian optimization, to explore the design space and report a 5 × reduction in simulations relative to grid-based search. Collectively, these results underscore the value of building intelligent design systems that leverage ML-based methods for uncovering key design variables and accelerating design.

Iterative Development of an Interactive Website to Support Shared Decision-Making in Metastatic Breast Cancer.

Recent treatment advances have resulted in significantly increased survival times following metastatic breast cancer (MBC) diagnosis. Novel treatment approaches-and their related side effects-have changed the landscape of MBC treatment decision-making. We developed a prototype of an online educational tool to prepare patients with MBC for shared decision-making with their oncologists. We describe the five phases of tool development: (1) in-depth, semi-structured qualitative interviews and (2) feedback on storyboards of initial content with patients with MBC and oncology providers. This was followed by three phases of iterative feedback with patients in which they responded to (3) initial, non-navigable website content and (4) a beta version of the full website. In the final phase (5), patients newly diagnosed with MBC (N = 6) used the website prototype for 1 week and completed surveys assessing acceptability, feasibility, treatment knowledge, preparation for decision-making, and self-efficacy for decision-making. Participants in Phase 1 characterized a cyclical process of MBC treatment decision-making and identified key information needs. Website content and structure was iteratively developed in Phases 2-4. Most participants in Phase 5 (n = 4) accessed the website 2-5 times. All participants who accessed the website at least once (n = 5) felt they learned new information from the website prototype and would recommend it to others newly-diagnosed with MBC. After using the website prototype, participants reported high preparation and self-efficacy for decision-making. This multiphase, iterative process resulted in a prototype intervention designed to support decision-making for MBC patients.

Deformation-encoding Deep Learning Transformer for High-Frame-Rate Cardiac Cine MRI.

Purpose To develop a deep learning model for increasing cardiac cine frame rate while maintaining spatial resolution and scan time. Materials and Methods A transformer-based model was trained and tested on a retrospective sample of cine images from 5840 patients (mean age, 55 years ± 19 [SD]; 3527 male patients) referred for clinical cardiac MRI from 2003 to 2021 at nine centers; images were acquired using 1.5- and 3-T scanners from three vendors. Data from three centers were used for training and testing (4:1 ratio). The remaining data were used for external testing. Cines with downsampled frame rates were restored using linear, bicubic, and model-based interpolation. The root mean square error between interpolated and original cine images was modeled using ordinary least squares regression. In a prospective study of 49 participants referred for clinical cardiac MRI (mean age, 56 years ± 13; 25 male participants) and 12 healthy participants (mean age, 51 years ± 16; eight male participants), the model was applied to cines acquired at 25 frames per second (fps), thereby doubling the frame rate, and these interpolated cines were compared with actual 50-fps cines. The preference of two readers based on perceived temporal smoothness and image quality was evaluated using a noninferiority margin of 10%. Results The model generated artifact-free interpolated images. Ordinary least squares regression analysis accounting for vendor and field strength showed lower error (P < .001) with model-based interpolation compared with linear and bicubic interpolation in internal and external test sets. The highest proportion of reader choices was "no preference" (84 of 122) between actual and interpolated 50-fps cines. The 90% CI for the difference between reader proportions favoring collected (15 of 122) and interpolated (23 of 122) high-frame-rate cines was -0.01 to 0.14, indicating noninferiority. Conclusion A transformer-based deep learning model increased cardiac cine frame rates while preserving both spatial resolution and scan time, resulting in images with quality comparable to that of images obtained at actual high frame rates. Keywords: Functional MRI, Heart, Cardiac, Deep Learning, High Frame Rate Supplemental material is available for this article. © RSNA, 2024.

Patterns and Predictors of Referral for Screening Breast MRI: A Mixed-Methods Study.

Introduction: Women with ≥20% lifetime breast cancer risk can receive supplemental breast cancer screening with MRI. We examined factors associated with recommendation for screening breast MRI among primary care providers (PCPs), gynecologists (GYNs), and radiologists. Methods: We conducted a sequential mixed-methods study. Quantitative: Participants (N = 72) reported recommendations for mammogram and breast MRI via clinical vignettes describing hypothetical patients with moderate, high, and very high breast cancer risk. Logistic regressions assessed the relationships of clinician-level factors (gender, specialty, years practicing) and practice-level factors (practice type, imaging facilities available) with screening recommendations. Qualitative: We interviewed a subset of survey participants (n = 17, 17/72 = 24%) regarding their decision-making about breast cancer screening recommendations. Interviews were audio-recorded, transcribed, and analyzed with directed content analysis. Results: Compared with PCPs, GYNs and radiologists were significantly more likely to recommend breast MRI for high-risk (ORs = 4.09 and 4.09, respectively) and very-high-risk patients (ORs = 8.56 and 18.33, respectively). Qualitative analysis identified two key phases along the clinical pathway for high-risk women. Phase 1 was "identifying high-risk women," which included three subthemes (systems for risk assessment, barriers to risk assessment, scope of practice issues). Phase 2 was "referral for screening," which included three subthemes (conflicting guidelines, scope of practice issues, legal implications). Frequency of themes differed between specialties, potentially explaining findings from the quantitative phase. Conclusions: There are significant differences between specialties in supplemental breast cancer screening recommendations. Multilevel interventions are needed to support identification and management of women with high breast cancer risk, particularly for PCPs.

Positive Charge Influences on the Surface Interactions and Cohesive Bonding of a Catechol-Containing Polymer.

Achieving robust underwater adhesion remains challenging. Through generations of evolution, marine mussels have developed an adhesive system that allows them to anchor onto wet surfaces. Scientists have taken varied approaches to developing mussel-inspired adhesives. Mussel foot proteins are rich in lysine residues, which may play a role in the removal of salts from surfaces. Displacement of water and ions on substrates could then enable molecular contact with surfaces. The necessity of cations for underwater adhesion is still in debate. Here, we examined the performance of a methacrylate polymer containing quaternary ammonium and catechol groups. Varying amounts of charge in the polymers were studied. As opposed to protonated amines such as lysine, quaternary ammonium groups offer a nonreactive cation for isolating effects from only charge. Results shown for dry bonding demonstrated that cations tended to decrease bulk cohesion while increasing surface interactions. Stronger interactions at surfaces, along with weaker bulk bonding, indicate that cations decreased the cohesive forces. When under salt water, overall bulk adhesion also dropped with higher cation loadings. Surface attachment under salt water also dropped, indicating that the polymer cations could not displace surface waters or sodium ions. Salt did, however, appear to shield bulk cation-cation repulsions. These studies help to distinguish influences upon bulk cohesion from attachment at surfaces. The roles of cations in adhesion are complex, with both cohesive and surface bonding being relevant in different ways, sometimes even working in opposite directions.

Cardiovascular magnetic resonance characterization of myocardial tissue injury in a miniature swine model of cancer therapy-related cardiovascular toxicity.

BACKGROUND: Left ventricular ejection fraction (LVEF) is the most commonly clinically used imaging parameter for assessing cancer therapy-related cardiac dysfunction (CTRCD). However, LVEF declines may occur late, after substantial injury. This study sought to investigate cardiovascular magnetic resonance (CMR) imaging markers of subclinical cardiac injury in a miniature swine model. METHODS: Female Yucatan miniature swine (n = 14) received doxorubicin (2 mg/kg) every 3 weeks for 4 cycles. CMR, including cine, tissue characterization via T1 and T2 mapping, and late gadolinium enhancement (LGE) were performed on the same day as doxorubicin administration and 3 weeks after the final chemotherapy cycle. In addition, magnetic resonance spectroscopy (MRS) was performed during the 3 weeks after the final chemotherapy in 7 pigs. A single CMR and MRS exam were also performed in 3 Yucatan miniature swine that were age- and weight-matched to the final imaging exam of the doxorubicin-treated swine to serve as controls. CTRCD was defined as histological early morphologic changes, including cytoplasmic vacuolization and myofibrillar loss of myocytes, based on post-mortem analysis of humanely euthanized pigs after the final CMR exam. RESULTS: Of 13 swine completing 5 serial CMR scans, 10 (77%) had histological evidence of CTRCD. Three animals had neither histological evidence nor changes in LVEF from baseline. No absolute LVEF <40% or LGE was observed. Native T1, extracellular volume (ECV), and T2 at 12 weeks were significantly higher in swine with CTRCD than those without CTRCD (1178 ms vs. 1134 ms, p = 0.002, 27.4% vs. 24.5%, p = 0.03, and 38.1 ms vs. 36.4 ms, p = 0.02, respectively). There were no significant changes in strain parameters. The temporal trajectories in native T1, ECV, and T2 in swine with CTRCD showed similar and statistically significant increases. At the same time, there were no differences in their temporal changes between those with and without CTRCD. MRS myocardial triglyceride content substantially differed among controls, swine with and without CTRCD (0.89%, 0.30%, 0.54%, respectively, analysis of variance, p = 0.01), and associated with the severity of histological findings and incidence of vacuolated cardiomyocytes. CONCLUSION: Serial CMR imaging alone has a limited ability to detect histologic CTRCD beyond LVEF. Integrating MRS myocardial triglyceride content may be useful for detection of early potential CTRCD.

MRI Assessment of Myocardial Deformation for Risk Stratification of Major Arrhythmic Events in Patients With Non-Ischemic Cardiomyopathy Eligible for Primary Prevention Implantable Cardioverter Defibrillators.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) intervention is an established prophylactic measure. Identifying high-benefit patients poses challenges. PURPOSE: To assess the prognostic value of cardiac magnetic resonance imaging (MRI) parameters including myocardial deformation for risk stratification of ICD intervention in non-ischemic cardiomyopathy (NICM) while accounting for competing mortality risk. STUDY TYPE: Retrospective and prospective. POPULATION: One hundred and fifty-nine NICM patients eligible for primary ICD (117 male, 54 ± 13 years) and 49 control subjects (38 male, 53 ± 5 years). FIELD STRENGTH/SEQUENCE: Balanced steady state free precession (bSSFP) and three-dimensional phase-sensitive inversion-recovery late gadolinium enhancement (LGE) sequences at 1.5 T or 3 T. ASSESSMENT: Patients underwent MRI before ICD implantation and were followed up. Functional parameters, left ventricular global radial, circumferential and longitudinal strain, right ventricular free wall longitudinal strain (RV FWLS) and left atrial strain were measured (Circle, cvi42). LGE presence was assessed visually. The primary endpoint was appropriate ICD intervention. Models were developed to determine outcome, with and without accounting for competing risk (non-sudden cardiac death), and compared to a baseline model including LGE and clinical features. STATISTICAL TESTS: Wilcoxon non-parametric test, Cox's proportional hazards regression, Fine-Gray competing risk model, and cumulative incidence functions. Harrell's c statistic was used for model selection. A P value <0.05 was considered statistically significant. RESULTS: Follow-up duration was 1176 ± 960 days (median: 896). Twenty-six patients (16%) met the primary endpoint. RV FWLS demonstrated a significant difference between patients with and without events (-12.5% ± 5 vs. -16.4% ± 5.5). Univariable analyses showed LGE and RV FWLS were significantly associated with outcome (LGE: hazard ratio [HR] = 3.69, 95% CI = 1.28-10.62; RV FWLS: HR = 2.04, 95% CI = 1.30-3.22). RV FWLS significantly improved the prognostic value of baseline model and remained significant in multivariable analysis, accounting for competing risk (HR = 1.73, 95% CI = 1.12-2.66). DATA CONCLUSIONS: In NICM, RV FWLS may provide additional predictive value for predicting appropriate ICD intervention. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 5.

Disease activity is associated with changes in the innate immune function in patients with systemic lupus erythematosus.

OBJECTIVE: To address the relationship between systemic lupus erythematosus (SLE) disease activity and the functional parameters of the innate immunity. METHODS: We evaluated a cohort of 26 adult SLE patients and 10 sex and age-paired healthy donors. When the patients had a disease flare (baseline) and when they achieve clinical response (follow-up), we assessed the systemic lupus erythematosus disease activity index 2 K (SLEDAI 2 K) and the following parameters with flow cytometry and confocal microscopy: monocyte subsets, their expression of TLR2, phagocytic monocytes and neutrophils using the pHrodo Red E. coli BioParticles, the respiratory burst with 123-dihydrorhodamine in neutrophils, and the spontaneous and lipopolysaccharide (LPS)-induced production of neutrophil extracellular traps (NETs). We used the Wilcoxon test to compare the paired medians with interquartile range (IQR) and the Mann-Whitney U test for independent medians. To assess the effect of prednisone and SLEDAI 2 K on the mentioned parameters, we applied a generalized mixed linear model. RESULTS: Twenty-three patients (88.4%) were women. The SLEDAI 2 K was higher at baseline 8 (6-14) in comparison to that at follow-up (6 (4-8), P = 0.028). At baseline, SLE patients had a decreased percentage of intermediate monocytes, a higher expression of TLR2 in total monocytes, increased phagocytosis in monocytes and neutrophils, a decreased respiratory burst intensity, and an increased production of NETs. In the mix model, the SLEDAI 2 K was the main factor influencing these functional innate immune parameters. CONCLUSION: Disease activity regulates the innate immune function in SLE which may contribute to the clinical features and infection predisposition. Key points • This is the first cohort study addressing the effect of disease activity and prednisone use on the innate immune function of lupus patients. • Our results show that the disease activity is a key regulator of the respiratory burst, phagocytosis, and the production of neutrophil extracellular traps. • Also, we observed a differential proportion of monocyte subsets according to SLE disease activity. • We consider that our manuscript contributes to the evidence addressing the intrinsic immune abnormalities of patients with SLE regardless of the use of immunosuppressants and set the bases for new research work considering the disease activity as an element to decide the prescription and duration of antibiotic prophylaxis in SLE patients, which is of interest to all rheumatologists.

Radiomics of Late Gadolinium Enhancement Reveals Prognostic Value of Myocardial Scar Heterogeneity in Hypertrophic Cardiomyopathy.

BACKGROUND: Late gadolinium enhancement (LGE) scar burden by cardiac magnetic resonance is a major risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). However, there is currently limited data on the incremental prognostic value of integrating myocardial LGE radiomics (ie, shape and texture features) into SCD risk stratification models. OBJECTIVES: The purpose of this study was to investigate the incremental prognostic value of myocardial LGE radiomics beyond current European Society of Cardiology (ESC) and American College of Cardiology (ACC)/American Heart Association (AHA) models for SCD risk prediction in HCM. METHODS: A total of 1,229 HCM patients (62% men; age 52 ± 16 years) from 3 medical centers were included. Left ventricular myocardial radiomic features were calculated from LGE images. Principal component analysis was used to reduce the radiomic features and calculate 3 principal radiomics (PrinRads). Cox and logistic regression analyses were then used to evaluate the significance of the extracted PrinRads of LGE images, alone or in combination with ESC or ACC/AHA models, to predict SCD risk. The ACC/AHA risk markers include LGE burden using a dichotomized 15% threshold of LV scar. RESULTS: SCD events occurred in 30 (2.4%) patients over a follow-up period of 49 ± 28 months. Risk prediction using PrinRads resulted in higher c-statistics than the ESC (0.69 vs 0.57; P = 0.02) and the ACC/AHA (0.69 vs 0.67; P = 0.75) models. Risk predictions were improved by combining the 3 PrinRads with ESC (0.73 vs 0.57; P < 0.01) or ACC/AHA (0.76 vs 0.67; P < 0.01) risk scores. The net reclassification index was improved by combining the PrinRads with ESC (0.25 [95% CI: 0.08-0.43]; P = 0.005) or ACC/AHA (0.05 [95% CI: -0.07 to 0.16]; P = 0.42) models. One PrinRad was a significant predictor of SCD risk (HR: 0.57 [95% CI: 0.39-0.84]; P = 0.01). LGE heterogeneity was a major component of PrinRads and a significant predictor of SCD risk (HR: 0.07 [95% CI: 0.01-0.75]; P = 0.03). CONCLUSIONS: Myocardial LGE radiomics are strongly associated with SCD risk in HCM and provide incremental risk stratification beyond current ESC or AHA/ACC risk models. Our proof-of-concept study warrants further validation.

Scanner-Independent MyoMapNet for Accelerated Cardiac MRI T1 Mapping Across Vendors and Field Strengths.

BACKGROUND: In cardiac T1 mapping, a series of T1 -weighted (T1 w) images are collected and numerically fitted to a two or three-parameter model of the signal recovery to estimate voxel-wise T1 values. To reduce the scan time, one can collect fewer T1 w images, albeit at the cost of precision or/and accuracy. Recently, the feasibility of using a neural network instead of conventional two- or three-parameter fit modeling has been demonstrated. However, prior studies used data from a single vendor and field strength; therefore, the generalizability of the models has not been established. PURPOSE: To develop and evaluate an accelerated cardiac T1 mapping approach based on MyoMapNet, a convolution neural network T1 estimator that can be used across different vendors and field strengths by incorporating the relevant scanner information as additional inputs to the model. STUDY TYPE: Retrospective, multicenter. POPULATION: A total of 1423 patients with known or suspected cardiac disease (808 male, 57 ± 16 years), from three centers, two vendors (Siemens, Philips), and two field strengths (1.5 T, 3 T). The data were randomly split into 60% training, 20% validation, and 20% testing. FIELD STRENGTH/SEQUENCE: A 1.5 T and 3 T, Modified Look-Locker inversion recovery (MOLLI) for native and postcontrast T1 . ASSESSMENT: Scanner-independent MyoMapNet (SI-MyoMapNet) was developed by altering the deep learning (DL) architecture of MyoMapNet to incorporate scanner vendor and field strength as inputs. Epicardial and endocardial contours and blood pool (by manually drawing a large region of interest in the blood pool) of the left ventricle were manually delineated by three readers, with 2, 8, and 9 years of experience, and SI-MyoMapNet myocardial and blood pool T1 values (calculated from four T1 w images) were compared with conventional MOLLI T1 values (calculated from 8 to 11 T1 w images). STATISTICAL TESTS: Equivalency test with 95% confidence interval (CI), linear regression slope, Pearson correlation coefficient (r), Bland-Altman analysis. RESULTS: The proposed SI-MyoMapNet successfully created T1 maps. Native and postcontrast T1 values measured from SI-MyoMapNet were strongly correlated with MOLLI, despite using only four T1 w images, at both field-strengths and vendors (all r > 0.86). For native T1 , SI-MyoMapNet and MOLLI were in good agreement for myocardial and blood T1 values in institution 1 (myocardium: 5 msec, 95% CI [3, 8]; blood: -10 msec, 95%CI [-16, -4]), in institution 2 (myocardium: 6 msec, 95% CI [0, 11]; blood: 0 msec, [-18, 17]), and in institution 3 (myocardium: 7 msec, 95% CI [-8, 22]; blood: 8 msec, [-14, 30]). Similar results were observed for postcontrast T1 . DATA CONCLUSION: Inclusion of field strength and vendor as additional inputs to the DL architecture allows generalizability of MyoMapNet across different vendors or field strength. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Highly accelerated free-breathing real-time myocardial tagging for exercise cardiovascular magnetic resonance.

BACKGROUND: Exercise cardiovascular magnetic resonance (Ex-CMR) myocardial tagging would enable quantification of myocardial deformation after exercise. However, current electrocardiogram (ECG)-segmented sequences are limited for Ex-CMR. METHODS: We developed a highly accelerated balanced steady-state free-precession real-time tagging technique for 3 T. A 12-fold acceleration was achieved using incoherent sixfold random Cartesian sampling, twofold truncated outer phase encoding, and a deep learning resolution enhancement model. The technique was tested in two prospective studies. In a rest study of 27 patients referred for clinical CMR and 19 healthy subjects, a set of ECG-segmented for comparison and two sets of real-time tagging images for repeatability assessment were collected in 2-chamber and short-axis views with spatiotemporal resolution 2.0 × 2.0 mm2 and 29 ms. In an Ex-CMR study of 26 patients with known or suspected cardiac disease and 23 healthy subjects, real-time images were collected before and after exercise. Deformation was quantified using measures of short-axis global circumferential strain (GCS). Two experienced CMR readers evaluated the image quality of all real-time data pooled from both studies using a 4-point Likert scale for tagline quality (1-excellent; 2-good; 3-moderate; 4-poor) and artifact level (1-none; 2-minimal; 3-moderate; 4-significant). Statistical evaluation included Pearson correlation coefficient (r), intraclass correlation coefficient (ICC), and coefficient of variation (CoV). RESULTS: In the rest study, deformation was successfully quantified in 90% of cases. There was a good correlation (r = 0.71) between ECG-segmented and real-time measures of GCS, and repeatability was good to excellent (ICC = 0.86 [0.71, 0.94]) with a CoV of 4.7%. In the Ex-CMR study, deformation was successfully quantified in 96% of subjects pre-exercise and 84% of subjects post-exercise. Short-axis and 2-chamber tagline quality were 1.6 ± 0.7 and 1.9 ± 0.8 at rest and 1.9 ± 0.7 and 2.5 ± 0.8 after exercise, respectively. Short-axis and 2-chamber artifact level was 1.2 ± 0.5 and 1.4 ± 0.7 at rest and 1.3 ± 0.6 and 1.5 ± 0.8 post-exercise, respectively. CONCLUSION: We developed a highly accelerated real-time tagging technique and demonstrated its potential for Ex-CMR quantification of myocardial deformation. Further studies are needed to assess the clinical utility of our technique.