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Background Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome predominantly in women without usual cardiovascular risk factors. Many have a history of migraine headaches, but this association is poorly understood. This study aimed to determine migraine prevalence among SCAD patients and assess differences in clinical factors based on migraine history. Methods and Results A cohort study was conducted using the Mayo Clinic SCAD “Virtual” Multi‐Center Registry composed of patients with SCAD as confirmed on coronary angiography. Participant‐provided data and records were reviewed for migraine history, risk factors, SCAD details, therapies, and outcomes. Among 585 patients (96% women), 236 had migraine history; the lifetime and 1‐year prevalence of migraine were 40% and 26%, respectively. Migraine was more common in SCAD women than comparable literature‐reported female populations (42% versus 24%, P <0.0001; 42% versus 33%, P <0.0001). Among all SCAD patients, those with migraine history were more likely to be female (99.6% versus 94%; P =0.0002); have SCAD at a younger age (45.2±9.0 years versus 47.6±9.9 years; P =0.0027); have depression (27% versus 17%; P =0.025); have recurrent post‐SCAD chest pain at 1 month (50% versus 39%; P =0.035); and, among those assessed, have aneurysms, pseudoaneurysms, or dissections (28% versus 18%; P =0.018). There was no difference in recurrent SCAD at 5 years for those with versus without migraine (15% versus 19%; P =0.39). Conclusions Many SCAD patients have a history of migraine. SCAD patients with migraine are younger at the time of SCAD; have more aneurysms, pseudoaneurysms, and dissections among those imaged; and more often report a history of depression and post‐SCAD chest pain. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01429727, NCT01427179.

Study ObjectiveHigh‐dose intravenous vitamin C is a potential treatment option for patients with sepsis and may interfere with point‐of‐care (POC) blood glucose (BG) testing. This study aimed to determine if vitamin C dosing used for sepsis affected POC BG level results.DesignProspective observational pilot study.SettingIntensive care unit in a large academic tertiary care medical center.PatientsFive consecutive critically ill adults hospitalized between April 1 and June 1, 2017, who received two or more doses of intravenous vitamin C 1500 mg for the treatment of sepsis and had at least two paired POC BG levels and laboratory venous BG levels measured within 1 hour of each other during vitamin C therapy.Measurements and Main ResultsThe performance of POC BG level measurement was compared with the reference method of laboratory BG level measurement. The concordance to minimum accuracy criteria for BG meters set forth by the International Organization for Standardization (ISO) 15197:2013, the measurement of agreement between POC BG level and laboratory BG level using the Bland‐Altman method, and the clinical accuracy through Parkes error grid analysis were assessed. A total of 16 paired POC and laboratory BG level measurements from the five patients were included. The accuracy of POC BG with laboratory BG level measurements during vitamin C administration according to ISO 15197:2013 criteria was 81.3%, which did not meet the minimum accuracy criteria of 95%. The Bland‐Altman analysis showed a mean difference between POC and laboratory BG levels of 8.9 mg/dl, and the Parkes error grid analysis showed that the differences between POC and laboratory BG level measurements would not have resulted in a change in clinical action.ConclusionThe accuracy and agreement of POC and laboratory BG level measurements in critically ill patients receiving vitamin C were consistent with previously published reports in critically ill patients not receiving vitamin C and did not demonstrate clinically significant interference due to vitamin C dosing for sepsis.

Background: Risks and mechanisms of extension of conservatively managed spontaneous coronary artery dissection (SCAD) remain incompletely understood. Study objectives were to (1) evaluate mechanisms of early SCAD evolution through serial angiographic analysis, and (2) determine predictors of early SCAD progression. Methods and Results: Retrospective registry study of patients with SCAD managed with an initial conservative strategy (n=240). Patients who experienced significant SCAD progression within 14 days, defined as clinical worsening plus new critical coronary obstruction on repeat angiography, were compared with remaining controls. A total of 42 of 240 (17.5%) experienced significant SCAD progression after index conservative approach; 91% by day 6. Isolated intramural hematoma (IMH) at baseline (no intimal dissection) was observed more frequently in those experiencing progression compared with controls (69.1% versus 44.4%; P =0.004). Multivariable predictors of SCAD progression included lesion severity, multivessel involvement, and isolated IMH. To investigate mechanisms of SCAD evolution, all repeat angiograms ≤14 days were compared with corresponding baselines (n=82 patient angiogram pairs). Of those with isolated IMH at baseline, 20% developed intimal dissection at repeat study. IMH was associated with greater longitudinal lesion extension (11.5 versus 2.8 mm; P =0.01), worsening Thrombolysis in Myocardial Infarction flow (−0.8 versus 0.1; P =0.003), and a nonsignificant lower rate of angiographic improvement (20.0% versus 31.3%; P =0.16) compared with the group with baseline intimal dissection. Optical coherence tomography subgroup analysis (n=17) indicated intimo-medial thickness to be lowest at the midpoint of IMH. Conclusions: Conservatively managed SCAD carries a 1:6 hazard for serious deterioration within 6 days. The risk was higher in those with isolated IMH at baseline. IMH often precedes development of intimal dissection, which has implications for mechanisms of SCAD.

The TP53 tumor-suppressor gene is mutated in >50% of human tumors and Li-Fraumeni patients with germ line inactivation are predisposed to developing cancer. Here, we generated tp53 deleted zebrafish that spontaneously develop malignant peripheral nerve-sheath tumors, angiosarcomas, germ cell tumors, and an aggressive Natural Killer cell-like leukemia for which no animal model has been developed. Because the tp53 deletion was generated in syngeneic zebrafish, engraftment of fluorescent-labeled tumors could be dynamically visualized over time. Importantly, engrafted tumors shared gene expression signatures with predicted cells of origin in human tissue. Finally, we showed that tp53del/del enhanced invasion and metastasis in kRASG12D-induced embryonal rhabdomyosarcoma (ERMS), but did not alter the overall frequency of cancer stem cells, suggesting novel pro-metastatic roles for TP53 loss-of-function in human muscle tumors. In summary, we have developed a Li-Fraumeni zebrafish model that is amenable to large-scale transplantation and direct visualization of tumor growth in live animals.

Objectives: To investigate the role of endothelial function in patients with previous spontaneous coronary artery dissection. Background: Mechanisms underlying spontaneous coronary artery dissection, including a possible contribution from endothelial dysfunction, remain poorly understood. Methods: This was a single center, retrospective study of patients with a prior spontaneous coronary artery dissection episode who underwent invasive endothelial function testing in the cardiac catheterization laboratory for evaluation of recurrent chest pain. Coronary epicardial and microvascular responses to acetylcholine, adenosine, and nitroglycerine were assessed. Findings were compared to a reference group of normal controls ( n=232). Results: A total of 10 patients with prior angiographically confirmed spontaneous coronary artery dissection were referred for coronary endothelial function testing. The median coronary flow reserve was 2.8 (interquartile range (IQR) 2.3, 3.6). The median change in coronary diameter with acetylcholine was −0.9% (IQR −23.9, 4.2). The median increase in peak coronary blood flow following acetylcholine administration was 91.4% (IQR 9.1, 105.7), which was similar to the response observed in a reference group of patients (median age 51 years, 96% women) from our laboratory with normal microvascular responses to acetylcholine: 107.4% (IQR 75.5, 165.7; P=0.20). Four patients (40%) had an abnormal microvascular response to acetylcholine, with less than a 50% increase in coronary blood flow, and all but one patient had left anterior descending artery or multivessel spontaneous coronary artery dissection. Conclusion: Coronary epicardial and microvascular vasomotor dysfunction is not a predominant feature of spontaneous coronary artery dissection. Endothelial dysfunction is not implicated as the principal underlying mechanism.

Purpose Intermediate-risk rhabdomyosarcoma (RMS) includes patients with either nonmetastatic, unresected embryonal RMS (ERMS) with an unfavorable primary site or nonmetastatic alveolar RMS (ARMS). The primary aim of this study was to improve the outcome of patients with intermediate-risk RMS by substituting vincristine and irinotecan (VI) for half of vincristine, dactinomycin, and cyclophosphamide (VAC) courses. All patients received a lower dose of cyclophosphamide and earlier radiation therapy than in previous trials. Patients and Methods Patients were randomly assigned at study entry to either VAC (cumulative cyclophosphamide dose, 16.8 g/m 2 ) or VAC/VI (cumulative cyclophosphamide dose, 8.4 g/m 2 ) for 42 weeks of therapy. Radiation therapy started at week 4, with individualized local control plans permitted for patients younger than 24 months. The primary study end point was event-free survival (EFS). The study design had an 80% power (5% one-sided α-level) to detect an improved long-term EFS from 65% (with VAC) to 76% (with VAC/VI). Results A total of 448 eligible patients were enrolled in the study. At a median follow-up of 4.8 years, the 4-year EFS was 63% with VAC and 59% with VAC/VI ( P = .51), and 4-year overall survival was 73% for VAC and 72% for VAC/VI ( P = .80). Within the ARMS and ERMS subgroups, no difference in outcome by treatment arm was found. Severe hematologic toxicity was less common with VAC/VI therapy. Conclusion The addition of VI to VAC did not improve EFS or OS for patients with intermediate-risk RMS. VAC/VI had less hematologic toxicity and a lower cumulative cyclophosphamide dose, making VAC/VI an alternative standard therapy for intermediate-risk RMS.