Heterozygous variants in TBCK cause a mild neurologic syndrome in humans and mice.

TBCK-related encephalopathy is a rare pediatric neurodegenerative disorder caused by biallelic loss-of-function variants in the TBCK gene. After receiving anecdotal reports of neurologic phenotypes in both human and mouse TBCK heterozygotes, we quantified if TBCK haploinsufficiency causes a phenotype in mice and humans. Using the tbck+/- mouse model, we performed a battery of behavioral assays and mTOR pathway analysis to investigate potential alterations in neurophysiology. We conducted as well a phenome-wide association study (PheWAS) analysis in a large adult biobank to determine the presence of potential phenotypes associated to this variant. The tbck+/- mouse model demonstrates a reduction of exploratory behavior in animals with significant sex and genotype interactions. The concurrent PheWAS analysis of 10,900 unrelated individuals showed that patients with one copy of a TBCK loss-of-function allele had a significantly higher rate of acquired toe and foot deformities, likely indicative of a mild peripheral neuropathy phenotype. This study presents an example of what may be the underappreciated occurrence of mild neurogenic symptoms in heterozygote individuals of recessive neurogenetic syndromes.

Accuracy, uncertainty, and adaptability of automatic myocardial ASL segmentation using deep CNN.

PURPOSE: To apply deep convolution neural network to the segmentation task in myocardial arterial spin labeled perfusion imaging and to develop methods that measure uncertainty and that adapt the convolution neural network model to a specific false-positive versus false-negative tradeoff. METHODS: The Monte Carlo dropout U-Net was trained on data from 22 subjects and tested on data from 6 heart transplant recipients. Manual segmentation and regional myocardial blood flow were available for comparison. We consider 2 global uncertainty measures, named "Dice uncertainty" and "Monte Carlo dropout uncertainty," which were calculated with and without the use of manual segmentation, respectively. Tversky loss function with a hyperparameter ß was used to adapt the model to a specific false-positive versus false-negative tradeoff. RESULTS: The Monte Carlo dropout U-Net achieved a Dice coefficient of 0.91 ± 0.04 on the test set. Myocardial blood flow measured using automatic segmentations was highly correlated to that measured using the manual segmentation (R2 = 0.96). Dice uncertainty and Monte Carlo dropout uncertainty were in good agreement (R2 = 0.64). As ß increased, the false-positive rate systematically decreased and false-negative rate systematically increased. CONCLUSION: We demonstrate the feasibility of deep convolution neural network for automatic segmentation of myocardial arterial spin labeling, with good accuracy. We also introduce 2 simple methods for assessing model uncertainty. Finally, we demonstrate the ability to adapt the convolution neural network model to a specific false-positive versus false-negative tradeoff. These findings are directly relevant to automatic segmentation in quantitative cardiac MRI and are broadly applicable to automatic segmentation problems in diagnostic imaging.

Feasibility of coronary endothelial function assessment using arterial spin labeled CMR.

Coronary endothelial dysfunction (CED) is an independent predictor of cardiovascular disease, but its assessment has been limited to invasive coronary angiography. Myocardial perfusion imaging using arterial spin labeled (ASL) cardiac magnetic resonance (CMR) may be an effective non-invasive alternative for detection of CED. Thirty-four patients were recruited: 10 healthy volunteers, 13 at high-risk for coronary artery disease (CAD), and 11 with established CAD. ASL-CMR was performed continuously in a single mid-short axis slice during rest, stress, and recovery. Stress was induced with sustained isometric handgrip exercise, an endothelial dependent stressor. Myocardial perfusion (MP) during rest, peak stress, and recovery were calculated and compared. After excluding subjects unable to complete the protocol or who exhibited poor data quality, 6 healthy, 10 high-risk, and 7 CAD patients were included in the analysis. Average MP (ml/g/min) was 1.31 ± 1.23, 1.61 ± 1.12, and 1.40 ± 0.97 at rest, and 1.64 ± 1.49, 2.31 ± 1.61, and 2.84 ± 1.77 during stress, for the CAD, high-risk and healthy group, respectively. The average MP response (MPstress - MPrest , ml/g/min) was 0.32 ± 1.93, 0.69 ± 1.34, and 1.44 ± 1.46 for CAD, high-risk and healthy group, respectively. MP during handgrip stress was significantly lower for both the CAD (p = 0.0005) and high-risk groups (p = 0.05) compared to the healthy volunteers. In only the healthy subjects, MP was significantly higher in stress compared to rest (p = 0.0002). Participants with CAD had significantly lower MP response compared to healthy volunteers, as detected by ASL-CMR. These findings support the feasibility of ASL-CMR for non-invasive assessment of CED.

Double-gated myocardial ASL perfusion imaging is robust to heart rate variation.

PURPOSE: Cardiac motion is a dominant source of physiological noise (PN) in myocardial arterial spin labeled (ASL) perfusion imaging. This study investigates the sensitivity to heart rate variation (HRV) of double-gated myocardial ASL compared with the more widely used single-gated method. METHODS: Double-gating and single-gating were performed on 10 healthy volunteers (n = 10, 3F/7M; age, 23-34 years) and eight heart transplant recipients (n = 8, 1F/7M; age, 26-76 years) at rest in the randomized order. Myocardial blood flow (MBF), PN, temporal signal-to-noise ratio (SNR), and HRV were measured. RESULTS: HRV ranged from 0.2 to 7.8 bpm. Double-gating PN did not depend on HRV, while single-gating PN increased with HRV. Over all subjects, double-gating provided a significant reduction in global PN (from 0.20 ± 0.15 to 0.11 ± 0.03 mL/g/min; P = 0.01) and per-segment PN (from 0.33 ± 0.23 to 0.21 ± 0.12 mL/g/min; P < 0.001), with significant increases in global temporal SNR (from 11 ± 8 to 18 ± 8; P = 0.02) and per-segment temporal SNR (from 7 ± 4 to 11 ± 12; P < 0.001) without significant difference in measured MBF. CONCLUSION: Single-gated myocardial ASL suffers from reduced temporal SNR, while double-gated myocardial ASL provides consistent temporal SNR independent of HRV. Magn Reson Med 77:1975-1980, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Assessment of segmental myocardial blood flow and myocardial perfusion reserve by adenosine-stress myocardial arterial spin labeling perfusion imaging.

PURPOSE: To determine the feasibility of measuring increases in myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) on a per-segment basis using arterial spin labeled (ASL) magnetic resonance imaging (MRI) with adenosine vasodilator stress in normal human myocardium. MATERIALS AND METHODS: Myocardial ASL scans at rest and during adenosine infusion were incorporated into a routine 3T MR adenosine-induced vasodilator stress protocol and were performed in 10 healthy human volunteers. Myocardial ASL was performed using single-gated flow-sensitive alternating inversion recovery (FAIR) tagging and balanced steady-state free precession (bSSFP) imaging at 3T. A T2 -prep blood oxygen level-dependent (BOLD) SSFP sequence was used to concurrently assess segmental myocardial oxygenation with BOLD signal intensity (SI) percent change in the same subjects. RESULTS: There was a statistically significant difference between MBF measured by ASL at rest (1.75 ± 0.86 ml/g/min) compared to adenosine stress (4.58 ± 2.14 ml/g/min) for all wall segments (P < 0.0001), yielding a per-segment MPR of 3.02 ± 1.51. When wall segments were divided into specific segmental myocardial perfusion territories (ie, anteroseptal, anterior, anterolateral, inferolateral, inferior, and inferoseptal), the differences between rest and stress regional MBF for each territory remained consistently statistically significant (P < 0.001) after correcting for multiple comparisons. CONCLUSION: This study demonstrates the feasibility of measuring MBF and MPR on a segmental basis by single-gated cardiac ASL in normal volunteers. Second, this study demonstrates the feasibility of performing the ASL sequence and T2 -prepared SSFP BOLD imaging during a single adenosine infusion. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:413-420.

Predicting three-month functional outcomes after an ED visit for acute low back pain.

BACKGROUND: Nearly 30% of patients who present to an ED with acute, new onset, low back pain (LBP) report LBP-related functional impairment three months later. These patients are at risk of chronic LBP, a highly debilitating condition. It has been reported previously that functional impairment, depression, and psychosomatic symptomatology at the index visit are associated with poor LBP outcomes. We wished to replicate those findings in a cohort of ED patients, and also to determine if clinical features present at one week follow-up could predict three-month outcomes in individual patients. METHODS: This was a planned analysis of data from a randomized comparative effectiveness study of three analgesic combinations conducted in one ED. Patients were followed by telephone one week and three months post-ED visit. The primary outcome was a three-month Roland-Morris Disability Questionnaire (RMDQ) score >0, indicating the presence of LBP-related functional impairment. At the index visit, we measured functional impairment (using the RMDQ), depressive symptomatology (using the Patient Health Questionnaire depression module), and psychosomatic features (using the 5-item Cassandra scale). At the one-week follow-up, we ascertained the presence or absence of LBP. We built a logistic regression model in which all the predictors were entered and retained in the model, in addition to socio-demographic variables and dummy variables controlling for investigational medication. Results are reported as adjusted odds ratios (adjOR) with 95% CI. To determine if statistically significant associations could be used to predict three-month outcomes in individual patients, we then calculated positive and negative likelihood ratios [LR(+) and LR(-)] with 95% CI for those independent variables associated with the primary outcome. RESULTS: Of 295 patients who completed the study, 14 (5%) were depressed and 18 (6%) reported psychosomatic symptoms. The median index visit RMDQ score was 19 (IQR: 17, 21) indicating substantial functional impairment. One week after the ED visit, 193 (65%) patients reported presence of LBP. 294 patients provided a three-month RMDQ score, 88 of whom (30%, 95% CI: 25, 35%) reported a score >0. Neither depression (adjOR 0.7 [95% CI 0.2, 3.1]), psychosomatic symptomatology (adjOR 0.5 [95% CI 0.1, 2.0]), nor index visit functional impairment (adjOR 1.0 [95% CI 1.0, 1.1]) were associated with three-month outcome. Pain at one week was strongly and independently associated with the three-month outcome when examined at the group level (adjOR 4.0 [95% CI 2.1, 7.7]). However, likelihood ratios for pain or its absence at one-week were insufficiently robust to be clinically useful in predicting three-month outcomes in individual patients (LR+: 1.4 [95% CI: 1.3, 1.7]; LR-: 0.4 [95% CI: 0.2, 0.6]). CONCLUSIONS: In spite of a strong association at the group level between presence of LBP at one week and functional impairment at three months, when used to predict outcomes in individual patients, presence of pain failed to discriminate with clinically meaningful utility between acute LBP patients destined to have a favorable versus unfavorable three-month outcome.

Pan-Cardiac Cycle Fixed Mitral Valve Opening in an LVAD Patient Presenting with Hemorrhagic Shock.

We present the case of a patient with a HeartMate II left ventricular assist device (LVAD) who underwent an elective cholecystectomy and abruptly decompensated on postoperative day 9. We highlight the uncommon echocardiogram finding of mitral valve leaflets fixed widely open throughout the cardiac cycle during an LVAD suction event. Bedside echocardiographic confirmation of a suction event enabled the rapid diagnosis and intervention for hemorrhagic shock before blood tests and radiographic results were available. Acoustic image quality can be limited in LVAD patients, and awareness of this uncommon finding may increase specificity for the echocardiographic diagnosis of LVAD suction events.

Effectiveness of a virtual reality trainer for retention of tourniquet application skills for hemorrhage control among emergency medicine residents.

Background: With a rise in mass casualty incidents, training in hemorrhage control using tourniquets has been championed as a basic-and lifesaving-procedure for bystanders and medical professionals alike. The current standard for training is in-person (IP) courses, which can be limited based on instructor availability. Virtual reality (VR) has demonstrated the potential to improve the accuracy of certain medical tasks but has not yet been developed for hemorrhage control. The objective of this study was to evaluate the efficacy of a VR hemorrhage trainer in learner retention of tourniquet application when compared to traditional IP instructor teaching among a cohort of emergency medicine residents practicing in a Level I trauma center. Methods: This was a prospective, observational study of 53 emergency medicine residents at an inner-city program. Participants were randomly assigned to either the control or the VR group. On Day 0, all residents underwent a training session (IP vs. VR) for the proper, stepwise application of a tourniquet, as defined by the American College of Trauma Surgeons. Each participant was then assessed on the application of a tourniquet by a blinded instructor using the National Registry Hemorrhage Control Skills Lab rubric. After 3 months, each resident was reevaluated on the same rubric, with subsequent data analysis on successful tourniquet placement (measured as under 90 s) and time to completion. Results: Of the 53 participants, the IP training group had an initial pass rate of 97% (28/29) compared to 92% (22/24) in the VR group (p = 0.58). On retention testing, the IP training group had a pass rate of 95% (20/21) compared to 90% (18/20) in the VR group (p = 0.62). Stratifying the success of tourniquet placement by level of resident training did not demonstrate any statistically significant differences. Conclusions: In this pilot study of emergency medicine residents, we found no significant differences in successful hemorrhage control by tourniquet placement between those trained with VR compared to a traditional IP course among emergency medicine residents. While more studies with greater power are needed, the results suggest that VR may be a useful adjunct to traditional IP medical training.

Exudative retinal detachment caused by metastatic choriocarcinoma to the choroid.

BACKGROUND: Choriocarcinoma is an aggressive malignant tumor. It commonly invades the uterus, causing necrosis and hemorrhage through vascular invasion. Metastasis is also common, with the main areas affected being the lung, brain, liver, pelvis, vagina, spleen, intestine, and kidney. OBJECTIVES: To illustrate the presentation of a rare disease, metastatic choriocarcinoma to the eye, causing a retinal detachment, and to elucidate the characteristics and treatment of that rare disease. CASE REPORT: A 23-year-old woman presented to our Emergency Department with a left painful red eye with decreased visual acuity and was subsequently diagnosed with choriocarcinoma with metastasis to the lungs, brain, and choroid, causing a left exudative retinal detachment. CONCLUSION: Gestational choriocarcinoma with metastasis to the eye is a rare disease and a rare cause of exudative retinal detachment. In general, metastatic choriocarcinoma is highly curable with chemotherapy. However, metastasis to the eye, regardless of the type of tumor, portends a poor prognosis.

In Situ Simulation as a Quality Improvement Tool to Identify and Mitigate Latent Safety Threats for Emergency Department SARS-CoV-2 Airway Management: A Multi-Institutional Initiative.

BACKGROUND: In situ simulation has emerged as a powerful quality improvement (QI) tool in the identification of latent safety threats (LSTs). Following the first wave of SARS-CoV-2 at an urban epicenter of the disease, a multi-institutional collaborative was formed to integrate an in situ simulation protocol across five emergency departments (EDs) for systems improvement of acute airway management. METHODS: A prospective, multi-institutional QI initiative using two Plan-Do-Study-Act (PDSA) cycles was implemented across five EDs. Each institution conducted simulations involving mannequins in acute respiratory failure requiring definitive airways. Simulations and systems-based debriefs were standardized. LSTs were collected in an online database, focused on (1) equipment availability, (2) infection control, and (3) communication. RESULTS: From June 2020 through May 2021, 58 of 70 (82.9%) planned simulations were completed across five sites with 328 unique individual participants. Overall LSTs per simulation (7.00-4.69, p < 0.001) and equipment LSTs (3.00-1.46, p < 0.001) decreased from cycle 1 to cycle 2. Changes in mean LSTs for infection control and communication categories varied among sites. There was no correlation between total LSTs or any of the categories and team size. Number of beds occupied was significantly negatively correlated with total and infection control LSTs. CONCLUSION: This study was unique in simultaneously running a structured in situ protocol across numerous diverse institutions during a global pandemic. This initiative found similar categories of threats across sites, and the protocol developed empowered participants to implement changes to mitigate identified threats.

Safety Considerations for In Situ Simulation in Closed SARS-CoV-2 Units.

SUMMARY STATEMENT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic placed a tremendous strain on the healthcare system, which led to the deployment of new personnel into acute care settings, early graduation of medical students, and development of new treatment spaces. Education teams at the Montefiore Health System and New York Health and Hospitals/Jacobi Medical Center found simulation, both laboratory-based and in situ, critical to the training of medical staff and investigation of latent safety threats. Through our experience, we encountered unique infection control concerns based on in situ sessions, which prompted us to redesign our programs for the treatment of SARS-CoV-2. Using this experience, we outline our rationale for the use of in situ simulation for newly developed SARS-CoV-2 spaces along with recommendations on safety checks to consider before starting.

Using a Logic Model to Enable and Evaluate Long-Term Outcomes of a Mass Casualty Training Program: A Single Center Case Study.

PURPOSE: Global health disasters are on the rise and can occur at any time with little advance warning, necessitating preparation. The authors created a comprehensive evidence-based Emergency Preparedness Training Program focused on long-term retention and sustained learner engagement. METHOD: A prospective observational study was conducted of a simulation-based mass casualty event training program designed using an outcomes-based logic model. A total of 25 frontline healthcare workers from multiple hospital sites in the New York metropolitan area participated in an 8-hour immersive workshop. Data was collected from assessments, and surveys provided to participants 3 weeks prior to the workshop, immediately following the workshop, and 3 months after completion of the workshop. RESULTS: The mean percentage of total knowledge scores improved across pre-workshop, post-workshop and retention (3 months post-workshop) assessments (53.2% vs. 64.8% vs. 67.6%, P < 0.05). Average comfort scores in the core MCI competencies increased across pre-workshop, post-workshop and retention self-assessments (P < 0.01). Of the participants assessed at 3 months retention (n = 14, 56%), 50.0% (n = 7) assisted in updating their hospital's emergency operations plan and 50.0% (n = 7) pursued further self-directed learning in disaster preparedness medicine. CONCLUSIONS: The use of the logic model provided a transparent framework for the design, implementation, and evaluation of a competency-based EPT program at a single academic center.

Erratum: Discovery of a neuromuscular syndrome caused by biallelic variants in ASCC3.

[This corrects the article DOI: 10.1016/j.xhgg.2021.100024.].

Discovery of a neuromuscular syndrome caused by biallelic variants in ASCC3.

Activating Signal Cointegrator 1 Complex, Subunit 3 (ASCC3) is part of the four-part ASC-1 transcriptional cointegrator complex. This complex includes ASCC1 (associated with spinal muscular atrophy with congenital bone fractures 2), TRIP4 (associated with spinal muscular atrophy with congenital bone fractures 1), and ASCC2 (not yet associated with human disease.) ASCC3 encodes a DNA helicase responsible for generating single-stranded DNA as part of the DNA damage response. Interestingly, ASCC3 expresses coding and non-coding isoforms, which act in opposition to balance the recovery of gene transcription after UV-induced DNA damage. Here we report the discovery of ASCC3 as the cause of a neuromuscular syndrome in seven unreported individuals from six unrelated families and updates on the one previously reported family. All the individuals share a neurologic phenotype that ranges from severe developmental delay to muscle fatigue. There appears to be genotype-phenotype correlation, as the most mildly affected individual is homozygous for a rare missense variant, while the more severely affected individuals are compound heterozygotes for a missense and a presumed loss-of-function (LOF) variant. There are no individuals with biallelic presumed LOF variants in our cohort or in gnomAD, as this genotype may not be compatible with life. In summary we report a syndrome in these eleven individuals from seven families with biallelic variants in ASCC3.

Tolvaptan vs. furosemide-based diuretic regimens in patients hospitalized for heart failure with hyponatremia (AQUA-AHF).

AIMS: Hyponatremia is associated with poorer outcomes and diuretic response in patients hospitalized for heart failure. This study compared a tolvaptan-based vs. furosemide-based diuretic regimen on short-term clinical responses in hyponatremic acute heart failure. METHODS AND RESULTS: Prospective, randomized, open-label, parallel-group, single-centre study comparing oral tolvaptan vs. continuous infusion furosemide. Thirty-three subjects requiring hospitalization for acute congestive heart failure, and a serum sodium < 135 mmol/L, were randomized to tolvaptan 30 mg orally daily or furosemide 5 mg/h intravenously for initial 24 h, after which treatments could be escalated. Median daily dose throughout was tolvaptan 30 mg and furosemide 120 mg, with four subjects in each group requiring dose escalation. Urine output and net fluid balance were not different between groups at 24 h or subsequent time points up to 96 h. Changes in estimated glomerular filtration rate were comparable. Cystatin C improved at 24 h with tolvaptan compared with furosemide (-6.4 ± 11.8 vs. 4.1 ± 17.2% change, P = 0.036), but the effect was transient. No significant between group differences were seen for NT-proBNP, plasma renin activity, or urinary neutrophil gelatinase-associated lipocalin:Cr. Serum sodium, as well as copeptin levels, increased with tolvaptan compared with furosemide. CONCLUSIONS: Oral tolvaptan was associated with similar, but not superior, diuresis compared with intravenous furosemide for acute heart failure with concomitant hyponatremia.

Cap-dependent translational inhibition establishes two opposing morphogen gradients in Drosophila embryos.

In the early Drosophila embryo, asymmetric distribution of transcription factors, established as a consequence of translational control of their maternally derived mRNAs, initiates pattern formation . For instance, translation of the uniformly distributed maternal hunchback (hb) mRNA is inhibited at the posterior to form an anterior-to-posterior protein concentration gradient along the longitudinal axis . Inhibition of hb mRNA translation requires an mRNP complex (the NRE complex), which consists of Nanos (Nos), Pumilio (Pum), and Brain tumor (Brat) proteins, and the Nos responsive element (NRE) present in the 3' UTR of hb mRNA . The identity of the mRNA 5' effector protein that is responsible for this translational inhibition remained elusive. Here we show that d4EHP, a cap binding protein that represses caudal (cad) mRNA translation , also inhibits hb mRNA translation by interacting simultaneously with the mRNA 5' cap structure (m(7)GpppN, where N is any nucleotide) and Brat. Thus, by regulating Cad and Hb expression, d4EHP plays a key role in establishing anterior-posterior axis polarity in the Drosophila embryo.

The effect of beta-blockers on the diagnostic accuracy of vasodilator pharmacologic SPECT myocardial perfusion imaging.

BACKGROUND: The effect of beta (beta) blockers on the accuracy, particularly the sensitivity, of vasodilator radionuclide myocardial perfusion imaging (MPI) is not entirely clear. This study aimed to further assess the effect of beta-blockers on the ability of MPI to identify significant and high-risk coronary artery disease (CAD). METHODS AND RESULTS: For 555 patients who underwent vasodilator MPI and had coronary angiography within 90 days, global and per-vessel sensitivities and specificities were calculated, and were found to be similar between patients taking beta-blockers and those who were not. beta-blockers did not decrease the ability to detect patients with multivessel disease. Summed stress scores and summed rest scores were likewise similar in both groups. To account in part for catheterization referral bias and the potential of false-negative MPI studies in patients receiving beta-blockers, survival analysis was performed on 2646 patients with normal MPI studies who did not undergo cardiac catheterization and failed to demonstrate significant mortality difference related to the taking of beta-blockers. CONCLUSIONS: beta-blocker therapy does not diminish the ability of vasodilator stress MPI to detect clinically significant CAD, nor hide the mortality risk of patients with normal studies not referred for catheterization.

Heart-brain interactions in mental stress-induced myocardial ischemia.

Myocardial ischemia that results from emotional provocation occurs in as many as 30% to 50% of patients with coronary artery disease during the discourse of their lives. This emotionally provoked or mental stress ischemia is associated with poor prognosis, with emerging treatment strategies. This article outlines the conceptual constructs that support the pathophysiologic underpinnings, and biobehavioral aspects associated with this mental stress ischemia. We review a biobehavioral model in which cognitive stress is transduced in the brain. The response of the brain to psychosocial stress is a highly sophisticated and integrated process by which sensory inputs are evaluated and appraised for their importance in relation to previous experience and current goals. The biologic consequences of such stress transduced in the central nervous system has its effect on cardiovascular flow and function through changes in autonomic balance, which result in various biologic processes that culminate in the perturbation of flow and function of the heart.

Churg-Strauss Syndrome Presenting as Acute Necrotizing Eosinophilic Myocarditis: Concise Review of the Literature.

BACKGROUND: Acute eosinophilic myocarditis (EM) is a rare form of heart failure that is characterized by myocardial eosinophilic infiltration usually in association with peripheral eosinophilia. The underlying cause is variable and can include allergic reactions, parasitic infection, idiopathic hypereosinophilic syndrome, malignancy, Loeffler's syndrome, Churg-Strauss syndrome (CSS), early giant cell myocarditis and malignancy. The course is potentially fatal, and early diagnosis and treatment with steroids is essential. CONCLUSION: Here, we present an illustrative case of eosinophilic myocarditis secondary to CSS followed by a brief review of epidemiology, pathogenesis, diagnosis and treatment of both disease entities.

Use of coronary artery calcium testing to improve coronary heart disease risk assessment in a lung cancer screening population: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Assessment of coronary artery calcium (CAC) during lung cancer screening chest computed tomography (CT) represents an opportunity to identify asymptomatic individuals at increased coronary heart disease (CHD) risk. We determined the improvement in CHD risk prediction associated with the addition of CAC testing in a population recommended for lung cancer screening. METHODS: We included 484 out of 6814 Multi-Ethnic Study of Atherosclerosis (MESA) participants without baseline cardiovascular disease who met U.S. Preventive Service Task Force CT lung cancer screening criteria and underwent gated CAC testing. 10 year-predicted CHD risks with and without CAC were calculated using a validated MESA-based risk model and categorized into low (<5%), intermediate (5%-10%), and high (≥10%). The net reclassification improvement (NRI) and change in Harrell's C-statistic by adding CAC to the risk model were subsequently determined. RESULTS: Of 484 included participants (mean age = 65; 39% women; 32% black), 72 (15%) experienced CHD events over the course of follow-up (median = 12.5 years). Adding CAC to the MESA CHD risk model resulted in 17% more participants classified into the highest or lowest risk categories and a NRI of 0.26 (p = 0.001). The C-statistic improved from 0.538 to 0.611 (p = 0.01). CONCLUSIONS: CHD event rates were high in this lung cancer screening eligible population. These individuals represent a high-risk population who merit consideration for CHD prevention measures regardless of CAC score. Although overall discrimination remained poor with inclusion of CAC scores, determining whether those reclassified to an even higher risk would benefit from more aggressive preventive measures may be important.