Search

The Stress Survey Schedule is an instrument for measuring stress in the lives of persons with autism and other developmental disabilities. Development of the survey and analysis of the underlying measurement structure of the instrument is reported in three studies. Through the use of exploratory and confirmatory analysis procedures, eight dimensions of stress were identified: Anticipation/Uncertainty, Changes and Threats, Unpleasant Events, Pleasant Events, Sensory/Personal Contact, Food Related Activity, Social/Environmental Interactions, and Ritual Related Stress. These stress dimensions are highly relevant to the problems of autism and have not been addressed by other stress surveys. The information obtained from the Stress Survey can be used to plan for strategies to reduce the stress before it occurs or results in maladaptive behavior. [ABSTRACT FROM AUTHOR]

Background: Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this "cardiomyotoxicity" are lacking., Methods: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [ 95% confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated., Results: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events., Conclusions: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well., Trial Registration Number: NCT04294771 and NCT05454527.

Current mortality is low in cases of childhood acute leukemia. Dilated cardiomyopathy induced by anthracyclines remains the main cause of morbidity and mortality during mid-term and long-term follow-up. The aim of our study was to analyze the profile of left ventricular alterations in children treated with anthracyclines and to analyze risks and protective factors, including physical activity. Children and young adults with acute leukemia treated with anthracyclines between 2000 and 2018 during childhood were included. The physical activity performed by the patients before and after treatment was quantified in metabolic equivalent tasks, MET.h, per week. An echocardiographic assessment was performed, including strain analysis. Thirty-eight patients with a median age of 5 [3-8] years were included. Dilated cardiomyopathy was diagnosed in 3 patients and longitudinal strain abnormalities were observed in 11 patients (28.9%). Radiotherapy, cumulative anthracycline doses > 240 mg/m 2 , and the practice of physical activity > 14 MET.h per week (after leukemia treatment) were independently associated with strain abnormalities. In multivariate analysis, radiotherapy was significantly associated with an increased risk of LV GLS abnormalities (OR = 1.26 [1.01-1.57], p = 0.036), and physical activity > 14 MET.h/week after oncological treatment was significantly associated with a reduction in the risk of LV GLS abnormalities (OR of 0.03 [0.002-0.411], p = 0.009). The strain assessment of left ventricular function is an interesting tool for patient follow-up after leukemia treatment. Moderate and steady physical activity seems to be associated with fewer longitudinal strain abnormalities in patients treated with anthracyclines during childhood.

Immune checkpoint inhibitors (ICI) have transformed the therapeutic landscape in oncology. However, ICI can induce uncommon life-threatening autoimmune T-cell-mediated myotoxicities, including myocarditis and myositis. The thymus plays a critical role in T cell maturation. Here we demonstrate that thymic alterations are associated with increased incidence and severity of ICI myotoxicities. First, using the international pharmacovigilance database VigiBase, the Assistance Publique Hôpitaux de Paris-Sorbonne University data warehouse (Paris, France) and a meta-analysis of clinical trials, we show that ICI treatment of thymic epithelial tumors (TET, and particularly thymoma) was more frequently associated with ICI myotoxicities than other ICI-treated cancers. Second, in an international ICI myocarditis registry, we established that myocarditis occurred earlier after ICI initiation in patients with TET (including active or prior history of TET) compared to other cancers and was more severe in terms of life-threatening arrythmias and concurrent myositis, leading to respiratory muscle failure and death. Lastly, we show that presence of anti-acetylcholine-receptor antibodies (a biological proxy of thymic-associated autoimmunity) was more prevalent in patients with ICI myocarditis than in ICI-treated control patients. Altogether, our results highlight that thymic alterations are associated with incidence and seriousness of ICI myotoxicities. Clinico-radio-biological workup evaluating the thymus may help in predicting ICI myotoxicities., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Importance: Evidence is scarce on the effectiveness of simulation-based training in transesophageal echocardiography (TEE)., Objective: To assess the effectiveness of simulation-based teaching vs traditional teaching of TEE knowledge and skills of cardiology fellows., Design, Setting, and Participants: Between November 2020 and November 2021, all consecutive cardiology fellows inexperienced in TEE from 42 French university centers were randomized (1:1; n = 324) into 2 groups with or without simulation support., Main Outcomes and Measures: The co-primary outcomes were the scores in the final theoretical and practical tests 3 months after the training. TEE duration and the fellows' self-assessment of their proficiency were also assessed., Results: While the theoretical and practical test scores were similar between the 2 groups (324 participants; 62.6% male; mean age, 26.4 years) before the training (33.0 [SD, 16.3] points vs 32.5 [SD, 18.5] points; P = .80 and 44.2 [SD, 25.5] points vs 46.1 [SD, 26.1] points; P = .51, respectively), the fellows in the simulation group (n = 162; 50%) displayed higher theoretical test and practical test scores after the training than those in the traditional group (n = 162; 50%) (47.2% [SD, 15.6%] vs 38.3% [SD, 19.8%]; P < .001 and 74.5% [SD, 17.7%] vs 59.0% [SD, 25.1%]; P < .001, respectively). Subgroup analyses showed that the effectiveness of the simulation training was even greater when performed at the beginning of the fellowship (ie, 2 years or less of training) (theoretical test: an increase of 11.9 points; 95% CI, 7.2-16.7 vs an increase of 4.25 points; 95% CI, -1.05 to 9.5; P = .03; practical test: an increase of 24.9 points; 95% CI, 18.5-31.0 vs an increase of 10.1 points; 95% CI, 3.9-16.0; P < .001). After the training, the duration to perform a complete TEE was significantly lower in the simulation group than in the traditional group ( 8.3 [SD, 1.4] minutes vs 9.4 [SD, 1.2] minutes; P < .001, respectively). Additionally, fellows in the simulation group felt more ready and more confident about performing a TEE alone after the training (mean score, 3.0; 95% CI, 2.9-3.2 vs mean score, 1.7; 95% CI, 1.4-1.9; P < .001 and mean score, 3.3; 95% CI, 3.1-3.5 vs mean score, 2.4; 95% CI, 2.1-2.6; P < .001, respectively)., Conclusions and Relevance: Simulation-based teaching of TEE showed a significant improvement in the knowledge, skills, and self-assessment of proficiency of cardiology fellows, as well as a reduction in the amount of time needed to complete the examination. These results should encourage further investigation of clinical performance and patient benefits of TEE simulation training.

Background: Limited data are available regarding the optimal management and prognosis of patients with cancer who develop an acute myocardial infarction., Aim: The objective of this study was to analyse the characteristics and outcomes of patients according to cancer and myocardial infarction occurrence., Methods: Based on the French administrative hospital discharge database, the study collected information for all consecutive patients seen in French hospitals in 2013, excluding those with a history of myocardial infarction. The population was divided into two groups according to their history of cancer. We studied the following outcomes: all-cause and cardiovascular mortality; acute myocardial infarction; and ischaemic stroke. Data were collected after a 5-year follow-up., Results: Between 2013 and 2019, 3,381,472 patients were seen in French hospitals; among them, 3,323,757 had no history of myocardial infarction. Patients with a history of cancer (n=497,593) had higher incidences of all-cause mortality (17.82%/year vs 3.79%/year), cardiovascular mortality (1.61%/year vs 1.17%/year), myocardial infarction (0.82%/year vs 0.61%/year) and ischaemic stroke (0.91%/year vs 0.62%/year) compared with patients without cancer (n=2,826,164). After performing an adjusted competing-risk analysis, the cumulative incidence of acute myocardial infarction, cardiovascular death and ischaemic stroke incidence was found to be lower in patients with a history of cancer, whereas death of non-cardiac origin was more prevalent in patients with a history of cancer., Conclusions: In this observational study, we have shown that patients with cancer have a higher incidence of all-cause mortality, cardiovascular mortality and myocardial infarction. However, multivariable analysis showed a lower cumulative incidence of these events., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Competing Interests: Dr. Thuny has received congress support from Boehringer Ingelheim and Novartis. Dr. Bonaca is the executive director of CPC, a nonprofit academic research organization affiliated with the University of Colorado, that receives research grant/consulting funding from Abbott, Agios, Alexion Pharma, Alnylam, Amgen, Angionetics, Anthos, ARCA Biopharma, Array, AstraZeneca, Atentiv, Audentes, Bayer, Better Therapeutics, Brigham and Women’s Hospital, Bristol-Myers Squibb, Cardiol Therapeutics, CellResearch, Cook Medical, Cook, CSL Behring, Eidos Therapeutics, EP Trading Co, Esperion Therapeutics, EverlyWell, Faraday, Fortress Biotech, HDL Therapeutics, HeartFlow, Hummingbird Bioscience, Insmed, Janssen, Kowa Research, Lexicon, Merck, Medtronic, Moderna, Novate Medical, NovoNordisk, Pfizer, PhaseBio, PPD Development, Prairie Education and Research, Prothena Ciosciences, Regeneron, Regio Biosciences, Sanifit Therapeutics, Sanofi, Smith and Nephew, Stealth BioTherapeutics, University of Colorado, Worldwide Clinical Trials, Wraser, and Yale Cardiovascular Research Group; holds stock in Medtronic and Pfizer; and has received consulting fees from Audentes. Dr Cautela has received consulting fees from Janssen; lecture fees from Novartis, AstraZeneca, Janssen, and Vifor Pharma; and support for attending meetings from Novartis and AstraZeneca; and has participated on the advisory board or data safety monitoring board for Novartis.

Purpose: Immune checkpoint blocker (ICB) associated myocarditis (ICB-myocarditis) may present similarly and/or overlap with other cardiac pathology including acute coronary syndrome presenting a challenge for prompt clinical diagnosis., Methods: An international registry was used to retrospectively identify cases of ICB-myocarditis. Presence of coronary artery disease (CAD) was defined as coronary artery stenosis >70% in patients undergoing coronary angiogram., Results: Among 261 patients with clinically suspected ICB-myocarditis who underwent a coronary angiography, CAD was present in 59/261 patients (22.6%). Coronary revascularization was performed during the index hospitalisation in 19/59 (32.2%) patients. Patients undergoing coronary revascularization less frequently received steroids administration within 24 h of admission compared to the other groups (p = 0.029). Myocarditis-related 90-day mortality was 9/17 (52.7%) in the revascularised cohort, compared to 5/31 (16.1%) in those not revascularized and 25/156 (16.0%) in those without CAD (p = 0.001). Immune-related adverse event-related 90-day mortality was 9/17 (52.7%) in the revascularized cohort, compared to 6/31 (19.4%) in those not revascularized and 31/156 (19.9%) in no CAD groups (p = 0.007). All-cause 90-day mortality was 11/17 (64.7%) in the revascularized cohort, compared to 13/31 (41.9%) in no revascularization and 60/158 (38.0%) in no CAD groups (p = 0.10). After adjustment of age and sex, coronary revascularization remained associated with ICB-myocarditis-related death at 90 days (hazard ratio [HR] = 4.03, 95% confidence interval [CI] 1.84-8.84, p < 0.001) and was marginally associated with all-cause death (HR = 1.88, 95% CI, 0.98-3.61, p = 0.057)., Conclusion: CAD may exist concomitantly with ICB-myocarditis and may portend a poorer outcome when revascularization is performed. This is potentially mediated through delayed diagnosis and treatment or more severe presentation of ICB-myocarditis., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LL has served on the advisory board for Daiichi Sankyio, Senaca, Astra Zeneca and Servier, as an external expert for Astra Zeneca and received speakers' honoraria from Novartis and MSD. LL is receiving grants from the German Center for Cardiovascular Research (DZHK), German Reuter Foundation (DFG) LE3570/2-1; 3570/3-1 and grant 01KC2006B from the Federal Ministry for Education and Research (BMBF). DA received speakers’ honoraria from BMS, Ipsen and participated to ad-boards from Sanofi and AstraZeneca. KT has received honoraria from Bristol Myers Squibb, Pfizer, Ono Pharmaceutical, Merck BioPharma, Bayer, and grants from Otsuka, Daiichi, Sankyo and Takeda. JM has served on advisory boards for Bristol Myers Squibb, Takeda, Regeneron, Audentes, Deciphera, Ipsen, Janssen, ImmunoCore, Boston Biomedical, Amgen, Myovant, Triple Gene/Precigen, Cytokinetics and AstraZeneca and supported by NIH grants (R01HL141466, R01HL155990, R01HL156021). JES have received consultancy fees from BMS, BeiGene, AstraZeneca, Novartis, and grants from BMS, Novartis, French Agence Nationale de la Recherche, Fondation Coeur et Recherche, Fédération Française de Cardiologie. All other authors have nothing to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Hypothesis: Self-assembling molecular structures responding to light stimulus are appealing for applications as sensing and drug delivery. Supramolecular nanotubes have a relevant potential in nanotechnology as they can be used to encapsulate different loads like drugs, biological macromolecules, and nanomaterials. In addition, they are suitable elements for novel supracolloidal materials. Structural responses of supramolecular nanotubes to non-invasive stimuli are very much desired to enable controlled release of the encapsulated guests and to provide these recently developed new materials with an external trigger. Here, we describe the formation of well-defined, single wall tubules that interconvert into twisted ribbons upon UV-light exposure in aqueous environment. The structures are provided by self-assembly of an azobenzene substituted cholic acid, a biological surfactant belonging to the family of bile acids. The azobenzene group allows for the light responsiveness of the molecular packing. Concurrently the steroidal moieties assure both chiral features and extensive hydrophobic interactions for time and temperature resistant aggregates., Experiments: The molecular packing interconversion was followed by circular dichroism. Microscopy, small angle X-ray scattering and light scattering measurements demonstrated the drastic morphological variation upon irradiation. A model of the molecular arrangement within the tubular walls was suggested based on the circular dichroism spectra simulation., Findings: Innovatively, the molecular design reported in our work allows for encoding in the same light responsive system multiple desirable features (e.g. bio-origin, temperature resistance and chirality of the aggregates). Such combination of properties, never reported before for a single molecule, might be relevant for the realization of robust, stimuli-responsive bio-vectors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background Cardiac MRI features are not well-defined in immune checkpoint inhibitor (ICI)-induced myocarditis (ICI-M), a severe complication of ICI therapy in patients with cancer. Purpose To analyze the cardiac MRI features of ICI-M and to explore their prognostic value in major adverse cardiovascular events (MACE). Materials and Methods In this retrospective study from May 2017 to January 2020, cardiac MRI findings (including late gadolinium enhancement [LGE], T1 and T2 mapping, and extracellular volume fraction [ECV] z scores) of patients with ICI-M were compared with those of patients with cancer scheduled to receive ICI therapy (pre-ICI group) and patients with viral myocarditis. As a secondary objective, the potential value of cardiac MRI for predicting MACE in patients with ICI-M by using Cox proportional hazards models was explored. Results Thirty-three patients with ICI-M (mean age ± standard deviation, 68 years ± 14; 23 men) were compared with 21 patients scheduled to receive to ICI therapy (mean age, 65 years ± 14; 14 men) and 85 patients with viral myocarditis (mean age, 32 years ± 13; 67 men). Compared with the pre-ICI group, patients with ICI-M showed higher global native T1, ECV, and T2 z scores (0.03 ± 0.85 vs 1.79 ± 1.93 [ P < .001]; 1.34 ± 0.57 vs 2.59 ± 1.97 [ P = .03]; and -0.76 ± 1.41 vs 0.88 ± 1.96 [ P = .002], respectively), and LGE was more frequently observed (27 of 33 patients [82%] vs two of 21 [10%]; P < .001). LGE was less frequent in patients with ICI-M than those with viral myocarditis (27 of 33 patients [82%] vs 85 of 85 [100%]; P < .001) but was more likely to involve the septal segments (16 of 33 patients [48%] vs 25 of 85 [29%]; P < .001) and midwall layer (11 of 33 patients [33%] vs two of 85 [2%]; P < .001). Septal LGE was the only cardiac MRI predictor of MACE at 1 year even after adjustment for peak troponin (adjusted hazard ratio, 2.7 [95% CI: 1.1, 6.7]; P = .03). Conclusion Cardiac MRI features of immune checkpoint inhibitor (ICI)-induced myocarditis (ICI-M) seem to differ from those in patients scheduled to receive ICIs and patients with viral myocarditis. Septal late gadolinium enhancement might be a predictor of major cardiovascular events in patients with ICI-M. Clinical trial registration no. NCT03313544 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Edelman and Pursnani in this issue.

Background: Immune-checkpoint inhibitor-associated myocarditis (ICI-myocarditis) often presents with arrhythmias, but the prognostic value of early electrocardiogram findings is unclear. Although ICI-myocarditis and acute cellular rejection (ACR) following cardiac transplantation use similar treatment strategies, differences in arrhythmia burden are unknown., Objective: To evaluate the association of electrocardiogram findings in ICI-myocarditis with myocarditis-related mortality and life-threatening arrhythmia., Methods: A total of 125 cases of ICI-myocarditis were identified retrospectively across 49 hospitals worldwide; 50 cases of grade 2R or 3R ACR were included as comparators. Two cardiologists blinded to clinical data interpreted electrocardiograms. Associations between electrocardiogram features, myocarditis-related mortality and the composite of myocarditis-related mortality and life-threatening arrhythmias were examined. Adjusted hazard ratios (aHRs) were calculated., Results: The cohort had 78 (62.4%) men; median (interquartile range) age was 67 (58-76) years. At 30 days, myocarditis-related mortality was 20/124 (16.1%), and 28/124 (22.6%) met the composite endpoint. Patients who developed complete heart block (aHR by subdistribution hazards model [aHR(sh)] 3.29, 95% confidence interval [CI] 1.24-8.68; P=0.02) or life-threatening cardiac arrhythmias (aHR(sh) 6.82, 95% CI: 2.87-16.21; P<0.001) had a higher risk of myocarditis-related mortality. Pathological Q waves (aHR(sh) 3.40, 95% CI: 1.38-8.33; P=0.008), low QRS voltage (aHR(sh) 6.05, 95% CI: 2.10-17.39; P<0.001) and Sokolow-Lyon index (aHR(sh)/mV 0.54, 95% CI: 0.30-0.97; P=0.04) on admission electrocardiogram were also associated with increased risk of myocarditis-related mortality. These associations were mirrored in the composite outcome analysis. Compared with ACR, ICI-myocarditis had a higher incidence of life-threatening cardiac arrhythmias (15/125 [12.0%] vs 1/50 [2%]; P=0.04) and third-degree heart block (19/125 [15.2%] vs 0/50 [0%]; P=0.004)., Conclusions: Electrocardiograms in ICI-myocarditis with ventricular tachycardias, heart block, low-voltage and pathological Q waves were associated with myocarditis-related mortality and life-threating arrhythmia. Arrhythmia burden in ICI-myocarditis exceeds that of ACR after heart transplant., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Opinion Statement: Vascular events have become an important issue in the overall management of cancer patients. They usually result from a combination of (i) direct or indirect toxicity of anticancer treatments, (ii) a higher prevalence of cardiovascular risk factors in cancer patients, and (iii) prolonged exposure to treatments due to an increasing patient survival rate. In addition to conventional chemotherapies and radiotherapy, targeted therapies and immunotherapies have been developed which improve the prognosis of cancer patients but sometimes at the cost of vascular toxicity, which can lead to systemic or pulmonary hypertension and arterial/venous thromboembolic events. Endothelial dysfunction, a procoagulant state and metabolic disorders are the three main pathophysiological patterns leading to cancer treatment-related vascular toxicity. This issue is challenging because serious vascular adverse events can necessitate cancer treatment being put on hold or stopped, which could compromise patient survival. In addition to increasing the risk of thrombotic adverse events, cancer therapies may lead to an increased risk of bleeding, especially in treatments with vascular endothelial growth factor inhibitors. Therefore, we can define vasculo-oncology as a part of the cardio-oncology specialty; its aims are to predict, prevent, screen, and treat vascular toxicity related to cancer treatments. While the level of evidence is low regarding the management of vascular toxicity during cancer therapy, cardiologists and specialists in vascular diseases should closely collaborate with oncologists and hematologists to determine the optimal strategy for each patient., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hypothesis: Sodium deoxycholate is a natural bile salt produced by animals and fulfilling important physiological processes. It is also used as dispersive surfactant and building block for self-assembled architectures in biology and material science. Although long debated, the study of its self-assembly in water is hereto incomplete and the models of the known aggregates are still controversial. This background suggests a complex scenario likely missing of additional mesophases., Experiments: Electron and optical microscopy techniques were crossed with SAXS data for the research., Findings: Novel rod, sponge, vesicle, lamellae, nanotube phases and reversible transitions among them arise at conditions (concentration, pH, temperature, ionic strength, ionic composition) fitting the physiological working environment of sodium deoxycholate. These findings enlarge the perspective towards different directions. The integration of the previous literature with this work removes any interpretative contradiction since all the structures cover the entire spectrum of phases expected for surfactants, thus being explained according to the Israelachvili's scheme. It is not trivial that a single molecule can show such a high structural variability. This fact highlights a very versatile system. Probably it is not a coincidence that it occurs in a multitasking biomolecule. These results furnish fundamental knowledge to clarify the bile salts' role in vivo., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)