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Background: Cardiovascular magnetic resonance (CMR) is a precise tool for the assessment of cardiac anatomy, function, and tissue composition. However, studies providing CMR reference values in adolescence are scarce. We aim to provide sex-specific CMR reference values for biventricular and atrial dimensions and function and myocardial relaxation times in this population., Methods: Adolescents aged 15-18 years with no known cardiovascular disease underwent a non-contrast 3-T CMR scan between March 2021 and October 2021. The imaging protocol included a cine steady-state free-precession sequence for the analysis of chamber size and function, as well as T2-GraSE and native MOLLI T1-mapping for the characterization of myocardial tissue., Findings: CMR scans were performed in 123 adolescents (mean age 16 ± 0.5 years, 52% girls). Mean left and right ventricular end-diastolic indexed volumes were higher in boys than in girls (91.7 ± 11.6 vs 78.1 ± 8.3 ml/m 2 , p < 0.001; and 101.3 ± 14.1 vs 84.1 ± 10.5 ml/m 2 , p < 0.001), as was the indexed left ventricular mass (48.5 ± 9.6 vs 36.6 ± 6.0 g/m 2 , p < 0.001). Left ventricular ejection fraction showed no significant difference by sex (62.2 ± 4.1 vs 62.8 ± 4.2%, p = 0.412), whereas right ventricular ejection fraction trended slightly lower in boys (55.4 ± 4.7 vs. 56.8 ± 4.4%, p = 0.085). Indexed atrial size and function parameters did not differ significantly between sexes. Global myocardial native T1 relaxation time was lower in boys than in girls (1215 ± 23 vs 1252 ± 28 ms, p < 0.001), whereas global myocardial T2 relaxation time did not differ by sex (44.4 ± 2.0 vs 44.1 ± 2.4 ms, p = 0.384). Sex-stratified comprehensive percentile tables are provided for most relevant cardiac parameters., Interpretation: This cross-sectional study provides overall and sex-stratified CMR reference values for cardiac dimensions and function, and myocardial tissue properties, in adolescents. This information is useful for clinical practice and may help in the differential diagnosis of cardiac diseases, such as cardiomyopathies and myocarditis, in this population., Funding: Instituto de Salud Carlos III (PI19/01704)., Competing Interests: Javier Sánchez-González is a Philips Healthcare employee. Carlos Real is funded by the Fundacion Interhospitalaria para la Investigación Cardiovascular. The remaining authors declare no conflicts of interest., (© 2023 The Author(s).)

Background and Purpose: Reperfusion therapy is the standard of care for ischaemic stroke; however, there is a need to identify new therapeutic targets able to ameliorate cerebral damage. Neutrophil β 1 adrenoceptors (β1AR) have been linked to neutrophil migration during exacerbated inflammation. Given the central role of neutrophils in cerebral damage during stroke, we hypothesize that β1AR blockade will improve stroke outcomes., Experimental Approach: Rats were subjected to middle cerebral artery occlusion-reperfusion to evaluate the effect on stroke of the selective β1AR blocker metoprolol (12.5 mg·kg -1 ) when injected i.v. 10 min before reperfusion., Key Results: Magnetic resonance imaging and histopathology analysis showed that pre-reperfusion i.v. metoprolol reduced infarct size. This effect was accompanied by reduced cytotoxic oedema at 24 h and vasogenic oedema at 7 days. Metoprolol-treated rats showed reduced brain neutrophil infiltration and those which infiltrated displayed a high proportion of anti-inflammatory phenotype (N2, YM1 + ). Additional inflammatory models demonstrated that metoprolol specifically blocked neutrophil migration via β1AR and excluded a significant effect on the glia compartment. Consistently, metoprolol did not protect the brain in neutrophil-depleted rats upon stroke. In patients suffering an ischaemic stroke, β1AR blockade by metoprolol reduced circulating neutrophil-platelet co-aggregates., Conclusions and Implications: Our findings describe that β1AR blockade ameliorates cerebral damage by targeting neutrophils, identifying a novel therapeutic target to improve outcomes in patients with stroke. This therapeutic strategy is in the earliest stages of the translational pathway and should be further explored., (© 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Introduction: Heart transplant (HT) survival has barely improved in the last decades, which is unsatisfactory for many HT recipients. The development of anti-human leukocyte antigen (anti-HLA) antibodies in HT patients is associated with a cardiac allograft dysfunction. The mechanisms leading to this damage are unclear. The Multimodality Evaluation Of Antibody-Mediated Injury In Heart Transplantation (LEONE-HT) study aimed to thoroughly describe the damage inflicted on the myocardium by anti-HLA antibodies., Methods and Analysis: The LEONE-HT study is a cohort study with a cross-sectional approach in which HT patients with positive anti-HLA antibodies are compared with coetaneous HT patients with negative anti-HLA antibodies. All patients will undergo a state-of-the-art multimodal assessment, including imaging techniques, coronary anatomy and physiology evaluations and histological and immunological analyses. The individual and combined primary outcomes of structural graft injuries and longitudinal secondary outcomes are to be compared between the exposed and non-exposed groups with univariate and multivariable descriptive analyses., Ethics and Dissemination: The LEONE-HT study is carried out in accordance with the principles set out in the Declaration of Helsinki and the International Conference on Harmonization guidelines for good clinical practice and following national laws and regulations. The study design, objectives and participant centers have been communicated to clinicaltrials.gov (NCT05184426). The LEONE-HT study counts on the support of patient associations to disseminate the objectives and results of the research. This study was funded by the Spanish Ministry of Science and Innovation and the Spanish Society of Cardiology.

Background: Carotid and femoral plaque burden is a recognized biomarker of cardiovascular disease risk. A new electronic-sweep 3-dimensional (3D)-matrix transducer method can improve the functionality and image quality of vascular ultrasound atherosclerosis imaging., Objectives: This study aimed to validate this method for plaque volume measurement in early and intermediate-advanced plaques in the carotid and femoral territories., Methods: Plaque volumes were measured ex vivo in pig carotid and femoral artery specimens by 3-dimensional vascular ultrasound (3DVUS) using a 3D-matrix (electronic-sweep) transducer and its associated 3D plaque quantification software, and were compared with gold-standard histology. To test the clinical feasibility and accuracy of the 3D-matrix transducer, an experiment was conducted in intermediate-high risk individuals with carotid and femoral atherosclerosis. The results were compared with those obtained using the previously validated mechanical-sweep 3D transducer and established 2-dimensional (2D)-based plaque quantification software., Results: In the ex vivo study, the authors assessed 19 atherosclerotic plaques (plaque volume, 0.76 µL-56.30 μL), finding strong agreement between measurements with the 3D-matrix transducer and the histological gold-standard (intraclass correlation coefficient [ICC]: 0.992; [95% CI: 0.978-0.997]). In the clinical analysis of 20 patients (mean age 74.6 ± 4.45 years; 40% men), the authors found 64 (36 carotid and 28 femoral) of 80 scanned territories with atherosclerosis (measured atherosclerotic volume, 10 μL-859 μL). There was strong agreement between measurements made from electronic-sweep and mechanical-sweep 3DVUS transducers (ICC: 0.997 [95% CI: 0.995-0.998]). Agreement was also high between plaque volumes estimated by the 2D and 3D plaque quantification software applications (ICC: 0.999 [95% CI: 0.998-0.999]). Analysis time was significantly shorter with the 3D plaque quantification software than with the 2D multislice approach with a mean time reduction of 46%., Conclusions: 3DVUS using new matrix transducer technology, together with improved 3D plaque quantification software, simplifies the accurate volume measurement of early (small) and intermediate-advanced plaques located in carotid and femoral arteries., Competing Interests: Funding Support and Author Disclosures This study was partially funded by grants from the Ministerio de Economia, Industria y Competividad (MEIC) with cofunding from the European Regional Development Fund (ERDF) (SAF2016-75580-R to Dr Bentzon) and (BES-2016-076633 to Dr Nogales). Research funding was also received from the Instituto de Salud Carlos III Spain (PIE16/00021 to Drs Bueno and Fuster). The CNIC is supported by the Ministerio de Ciencia, Innovacion y Universidades (MICINN) and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). This study forms part of a Master Research Agreement between the CNIC and Philips Healthcare. Drs Sánchez-González, Entrekin, and Collet-Billon are employees of Philips Healthcare. All other authors have reported that they have no relationships to disclose related to the contents of this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: In 2020, 282,421 new cases of cancer were diagnosed in Spain, and urological neoplasms (UN) were among the most frequent ones. Cancer treatment in eldery people is challenging due to fragility and comorbidities of these patients. To meet the needs of treating UN in the eldery, it is necessary to optimize healthcare resources, for which a deep analysis of cancer registries becomes mandatory. The objective of this work was to provide a detailed analysis of the incidence and mortality of UN in Spanish people over 65 years old in the last year 2020, as well as the estimates for the year 2040., Material and Methods: Incidence and mortality estimates were obtained from the GLOBOCAN database. The urological neoplasms that were included were: testicle, bladder, penis, kidney and prostate., Results: In 2020, 63,278 cases of UN were diagnosed in Spain. Most UN were much more frequent among patients >65 years old, except for testicular cancers. For the year 2040, an incidence increase of 41.5% is estimated, reaching 89,507 new cases of UN per year, with approximately 3 out of 4 patients being over 65 years old. Deaths in people over 65 will increase by 60.15% in 2040., Conclusion: In the next two decades, it is expected that new cases UN in people over 65 years will increase above 50%. For Healthcare systems to face it, greater financial and human resources, as well as multidisciplinary teams with experience and geriatric training will be necessary., (Copyright © 2021 AEU. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Case series have reported persistent cardiopulmonary symptoms, often termed long-COVID or post-COVID syndrome, in more than half of patients recovering from Coronavirus Disease 19 (COVID-19). Recently, alterations in microvascular perfusion have been proposed as a possible pathomechanism in long-COVID syndrome. We examined whether microvascular perfusion, measured by quantitative stress perfusion cardiac magnetic resonance (CMR), is impaired in patients with persistent cardiac symptoms post-COVID-19., Methods: Our population consisted of 33 patients post-COVID-19 examined in Berlin and London, 11 (33%) of which complained of persistent chest pain and 13 (39%) of dyspnea. The scan protocol included standard cardiac imaging and dual-sequence quantitative stress perfusion. Standard parameters were compared to 17 healthy controls from our institution. Quantitative perfusion was compared to published values of healthy controls., Results: The stress myocardial blood flow (MBF) was significantly lower [31.8 ± 5.1 vs. 37.8 ± 6.0 (μl/g/beat), P < 0.001] and the T2 relaxation time was significantly higher (46.2 ± 3.6 vs. 42.7 ± 2.8 ms, P = 0.002) post-COVID-19 compared to healthy controls. Stress MBF and T1 and T2 relaxation times were not correlated to the COVID-19 severity (Spearman r = -0.302, -0.070, and -0.297, respectively) or the presence of symptoms. The stress MBF showed a U-shaped relation to time from PCR to CMR, no correlation to T1 relaxation time, and a negative correlation to T2 relaxation time (Pearson r = -0.446, P = 0.029)., Conclusion: While we found a significantly reduced microvascular perfusion post-COVID-19 compared to healthy controls, this reduction was not related to symptoms or COVID-19 severity., Competing Interests: PD owns stock of Siemens and Bayer. AF was a shareholder of BOCAhealthcare GmbH. CS was an employer of Philips Healthcare. BP reported receiving personal fees from Bayer, Bristol Myers Squib, Daiichi Sankyo, Medscape, MSD, Novartis, Stealth Peptides, and Vifor Pharma, and grants and personal fees from Astra-Zeneca. CS and JS-G were employees of Philips Healthcare. CT, BP, and SK received funding from the DZHK (German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research) and personal fees from Servier, outside of the current work. SK received an unrestricted research grant from Philips Healthcare and received lecture honoraria from Medis, NL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Doeblin, Steinbeis, Scannell, Goetze, Al-Tabatabaee, Erley, Faragli, Pröpper, Witzenrath, Zoller, Stehning, Gerhardt, Sánchez-González, Alskaf, Kühne, Pieske, Tschöpe, Chiribiri and Kelle.)

Objective: Food addiction (FA) construct was introduced to reflect abnormal eating patterns that resemble behavioural ones found in substance use disorders. FA has been barely explored in anorexia nervosa (AN). This study evaluated FA occurrence and associated factors in a sample of patients with AN, distinguishing between restrictive and binge-purging subtypes and focussing on the influence of FA in the crossover diagnosis between them., Method: A sample of 116 patients with AN admitted for treatment seeking at an Bellvitge Hospital Eating Disorders Unit were included (72 restrictive [AN-R]; 44 binge-purge AN [AN-BP]), and eating-related, personality and psychopathological variables were assessed. Most participants were women (92.2%), mean age 27.1 years old (SD = 10.5)., Results: FA was more prevalent in patients with AN-BP compared to the AN-R group (75.0% and 54.2%, respectively). The patients with AN-R FA+, presented more similar ED symptomatology, general psychopathology and personality traits, with the AN-BP patients, than with the AN-R FA-., Conclusions: Patients with AN-R FA+, exhibit more similarities with the AN-BP subgroup than with the AN-R FA-. Thus, it is possible to hypothesise that the presence of FA might be an indicator of the possible crossover from AN-R to AN-BP., (© 2022 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Background: A first approach addressed to ascertain whether emotion regulation (ER) could be a transdiagnostic construct between eating disorders (EDs) and gambling disorder (GD) (through a joint clinical clustering analysis of both disorders) was performed by Munguía et al. (2021). Both conditions were represented by a severe, moderate, and low ER profile subgroups, according to the degree of ER difficulties. Results showed a linear relationship between the severity of ER difficulties and the severity of the disorder and the psychopathological state., Aims: Based on the aforementioned cross-sectional study, the objective of this longitudinal research was to explore the treatment response of the different ER subgroups., Methods: 459 adult patients (n = 277 ED; n = 182 GD) were included. Several clinical variables, as well as outcome indicators (after completing 16 weeks of cognitive-behavioral therapy), were evaluated., Results: The three subgroups found in the previous cross-sectional study were taken for the performance of the present research. ED and GD distribution in each subgroup replicates the one exposed by Munguía et al. (2021), as well as their characterization, considering psychopathology, disorder severity and personality traits. The low ER subgroup reported a better response to treatment, whereas the severe group had the highest rates of non-remission and dropouts., Conclusions: Our results suggest that greater difficulties in ER lead to poorer treatment outcomes. Therefore, tailored treatments for patients with poor ER abilities would be recommended to improve adherence and treatment outcomes.

Aims: The aim of this study was to study changes in coronary microcirculation status during and after several cycles of anthracycline treatment., Methods and Results: Large-white male pigs (n=40) were included in different experimental protocols (ExPr.) according to anthracycline cumulative exposure [0.45 mg/kg intracoronary (IC) doxorubicin per injection] and follow-up: control (no doxorubicin); single injection and sacrifice either at 48 h (ExPr. 1) or 2 weeks (ExPr. 2); 3 injections 2 weeks apart (low cumulative dose) and sacrifice either 2 weeks (ExPr. 3) or 12 weeks (ExPr. 4) after third injection; five injections 2 weeks apart (high cumulative dose) and sacrifice 8 weeks after fifth injection (ExPr. 5). All groups were assessed by serial cardiac magnetic resonance (CMR) to quantify perfusion and invasive measurement of coronary flow reserve (CFR). At the end of each protocol, animals were sacrificed for ex vivo analyses. Vascular function was further evaluated by myography in explanted coronary arteries of pigs undergoing ExPr. 3 and controls. A single doxorubicin injection had no impact on microcirculation status, excluding a direct chemical toxicity. A series of five fortnightly doxorubicin injections (high cumulative dose) triggered a progressive decline in microcirculation status, evidenced by reduced CMR-based myocardial perfusion and CFR-measured impaired functional microcirculation. In the high cumulative dose regime (ExPr. 5), microcirculation changes appeared long before any contractile defect became apparent. Low cumulative doxorubicin dose (three bi-weekly injections) was not associated with any contractile defect across long-term follow-up, but provoked persistent microcirculation damage, evident soon after third dose injection. Histological and myograph evaluations confirmed structural damage to arteries of all calibres even in animals undergoing low cumulative dose regimes. Conversely, arteriole damage and capillary bed alteration occurred only after high cumulative dose regime., Conclusion: Serial in vivo evaluations of microcirculation status using state-of-the-art CMR and invasive CFR show that anthracyclines treatment is associated with progressive and irreversible damage to the microcirculation. This long-persisting damage is present even in low cumulative dose regimes, which are not associated with cardiac contractile deficits. Microcirculation damage might explain some of the increased incidence of cardiovascular events in cancer survivors who received anthracyclines without showing cardiac contractile defects., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The COVID-19 lockdown has had a significant impact on mental health. Patients with eating disorders (ED) have been particularly vulnerable., Aims: (1) To explore changes in eating-related symptoms and general psychopathology during lockdown in patients with an ED from various European and Asian countries; and (2) to assess differences related to diagnostic ED subtypes, age, and geography., Methods: The sample comprised 829 participants, diagnosed with an ED according to DSM-5 criteria from specialized ED units in Europe and Asia. Participants were assessed using the COVID-19 Isolation Scale (CIES)., Results: Patients with binge eating disorder (BED) experienced the highest impact on weight and ED symptoms in comparison with other ED subtypes during lockdown, whereas individuals with other specified feeding and eating disorders (OFSED) had greater deterioration in general psychological functioning than subjects with other ED subtypes. Finally, Asian and younger individuals appeared to be more resilient., Conclusions: The psychopathological changes in ED patients during the COVID-19 lockdown varied by cultural context and individual variation in age and ED diagnosis. Clinical services may need to target preventive measures and adapt therapeutic approaches for the most vulnerable patients.

Poor performance in executive functions is observed in individuals with eating disorders (EDs). These impairments have usually been associated with the presence of comorbid psychopathology or with higher severity of EDs. However, few studies have explored the interaction between illness duration and deficits in executive functions. The present study investigates the association between ED duration and performance in decision-making, inhibitory control, and cognitive flexibility in the anorexia nervosa restrictive subtype (AN-R), bulimic/purging subtype (AN-BP), and binge spectrum disorders (BSDs) (namely, bulimia nervosa and binge eating disorder) among 116 women with EDs compared with 123 women healthy controls (HCs). Using cumulative survival analysis, we estimated the risk of deficits related to illness duration. Predictors of executive dysfunctions were assessed by regression analysis, including as potential predictors illness duration, severity of general psychopathology, and ED symptomatology. Results showed poor decision-making and cognitive flexibility in participants with EDs compared with HCs. ED duration was associated with poor inhibitory control in the AN-BP group and poor cognitive flexibility in the BSD group. The illness duration increased the risk of presenting early deficits in executive function. In decision-making and inhibitory control, the AN-R group showed the earliest deficits, whereas in cognitive flexibility it was the BSD group. ED duration predicted impaired cognitive flexibility in the BSD group and impaired inhibitory control in the AN-BP group, whereas the severity of general psychopathological symptoms was a predictor of impaired cognitive flexibility in individuals with AN-R. These results highlight the relevance of illness duration in executive dysfunctions in EDs., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Delayed gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging requires novel and time-efficient approaches to characterize the myocardial substrate associated with ventricular arrhythmia in patients with ischemic cardiomyopathy. Using a translational approach in pigs and patients with established myocardial infarction, we tested and validated a novel 3D methodology to assess ventricular scar using custom transmural criteria and a semiautomatic approach to obtain transmural scar maps in ventricular models reconstructed from both 3D-acquired and 3D-upsampled-2D-acquired LGE-CMR images. The results showed that 3D-upsampled models from 2D LGE-CMR images provided a time-efficient alternative to 3D-acquired sequences to assess the myocardial substrate associated with ischemic cardiomyopathy. Scar assessment from 2D-LGE-CMR sequences using 3D-upsampled models was superior to conventional 2D assessment to identify scar sizes associated with the cycle length of spontaneous ventricular tachycardia episodes and long-term ventricular tachycardia recurrences after catheter ablation. This novel methodology may represent an efficient approach in clinical practice after manual or automatic segmentation of myocardial borders in a small number of conventional 2D LGE-CMR slices and automatic scar detection., (© 2021. The Author(s).)

Objectives: This study sought to clinically validate a novel 3-dimensional (3D) ultrafast cardiac magnetic resonance (CMR) protocol including cine (anatomy and function) and late gadolinium enhancement (LGE), each in a single breath-hold., Background: CMR is the reference tool for cardiac imaging but is time-consuming., Methods: A protocol comprising isotropic 3D cine (Enhanced sensitivity encoding [SENSE] by Static Outer volume Subtraction [ESSOS]) and isotropic 3D LGE sequences was compared with a standard cine+LGE protocol in a prospective study of 107 patients (age 58 ± 11 years; 24% female). Left ventricular (LV) mass, volumes, and LV and right ventricular (RV) ejection fraction (LVEF, RVEF) were assessed by 3D ESSOS and 2D cine CMR. LGE (% LV) was assessed using 3D and 2D sequences., Results: Three-dimensional and LGE acquisitions lasted 24 and 22 s, respectively. Three-dimensional and LGE images were of good quality and allowed quantification in all cases. Mean LVEF by 3D and 2D CMR were 51 ± 12% and 52 ± 12%, respectively, with excellent intermethod agreement (intraclass correlation coefficient [ICC]: 0.96; 95% confidence interval [CI]: 0.94 to 0.97) and insignificant bias. Mean RVEF 3D and 2D CMR were 60.4 ± 5.4% and 59.7 ± 5.2%, respectively, with acceptable intermethod agreement (ICC: 0.73; 95% CI: 0.63 to 0.81) and insignificant bias. Both 2D and 3D LGE showed excellent agreement, and intraobserver and interobserver agreement were excellent for 3D LGE., Conclusions: ESSOS single breath-hold 3D CMR allows accurate assessment of heart anatomy and function. Combining ESSOS with 3D LGE allows complete cardiac examination in <1 min of acquisition time. This protocol expands the indication for CMR, reduces costs, and increases patient comfort., Competing Interests: Funding Support and Author Disclosures Funding included Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF) Grants DTS17/00136 to Dr. Ibáñez and PI19/01704 to Dr. Fernandez-Jimenez; Spanish Society of Cardiology Translational Research Grant 2016 to Dr. Ibáñez; European Research Council ERC-CoG 819775-MATRIX to Dr. Ibáñez; Comunidad de Madrid S2017/BMD-3867-RENIM-CM to Drs. Desco and Ibáñez; and Ministerio de Ciencia e Innovación (MICINN) RETOS2019-107332RB-I00 to Dr. Ibáñez. Dr. Fernandez-Jimenez received funding from the European Union Horizon 2020 research and innovation programme under Marie Skłodowska-Curie Hrant Agreement No. 707642. The CNIC is supported by the ISCIII, the MICINN, and the Pro CNIC Foundation. Drs. Fernandez-Jimenez, Nothnagel, Fuster, Ibáñez, and Javier Sánchez-González are inventors of a joint patent (Philips/CNIC) for the new cine imaging method here described and validated/protected under the IP #2014P00960EP. Drs. Nothnagel, Kouwenhoven, Clemence, and Javier Sánchez-González are Philips employees. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Eating disorders (EDs) are severe psychiatric illnesses that require individualized treatments. Decision-making deficits have been associated with EDs. Decision-making learning deficits denote a lack of strategies to elaborate better decisions that can have an impact on recovery and response to treatment. This study used the Iowa Gambling Task (IGT) to investigate learning differences related to treatment outcome in EDs, comparing between patients with a good and bad treatment outcome and healthy controls. Likewise, the predictive role of impaired learning performance on therapy outcome was explored. Four hundred twenty-four participants (233 ED patients and 191 healthy controls) participated in this study. Decision making was assessed using the Iowa Gambling Task before any psychological treatment. All patients received psychological therapy, and treatment outcome was evaluated at discharge. Patients with bad outcome did not show progression in the decision-making task as opposed to those with good outcome and the healthy control sample. Additionally, learning performance in the decision-making task was predictive of their future outcome. The severity of learning deficits in decision making may serve as a predictor of the treatment. These results may provide a starting point of how decision-making learning deficits are operating as dispositional and motivational factors on responsiveness to treatment in EDs.

The association between lifetime weight fluctuations and clinical characteristics has been widely studied in populations with eating disorders (ED). However, there is a lack of literature examining the potential role of weight course as a transdiagnostic factor in ED so far. Therefore, the aim of this study is to compare ED severity and treatment outcomes among four specific BMI profiles based on BMI-trajectories across the lifespan: (a) persistent obesity (OB-OB; ( n = 74)), (b) obesity in the past but currently in a normal weight range (OB-NW; n = 156), (c) normal weight throughout the lifespan (NW-NW; n = 756), and (d) current obesity but previously at normal weight (NW-OB; n = 314). Lifetime obesity is associated with greater general psychopathology and personality traits such as low persistence and self-directedness, and high reward dependence. Additionally, greater extreme weight changes (NW-OB and OB-NW) were associated with higher psychopathology but not with greater ED severity. Higher dropout rates were found in the OB-OB group. These results shed new light on the BMI trajectory as a transdiagnostic feature playing a pivotal role in the severity and treatment outcome in patients with ED.

Background: Quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) by cardiovascular magnetic resonance (CMR) perfusion requires sampling of the arterial input function (AIF). While variation in the AIF sampling location is known to impact quantification by CMR and positron emission tomography (PET) perfusion, there is no evidence to support the use of a specific location based on their diagnostic accuracy in the detection of coronary artery disease (CAD). This study aimed to evaluate the accuracy of stress MBF and MPR for different AIF sampling locations for the detection of abnormal myocardial perfusion with expert visual assessment as the reference., Methods: Twenty-five patients with suspected or known CAD underwent vasodilator stress-rest perfusion with a dual-sequence technique at 3T. A low-resolution slice was acquired in 3-chamber view to allow AIF sampling at five different locations: left atrium (LA), basal left ventricle (bLV), mid left ventricle (mLV), apical left ventricle (aLV) and aortic root (AoR). MBF and MPR were estimated at the segmental level using Fermi function-constrained deconvolution. Segments were scored as having normal or abnormal perfusion by visual assessment and the diagnostic accuracy of stress MBF and MPR for each location was evaluated using receiver operating characteristic curve analysis., Results: In both normal (300 out of 400, 75 %) and abnormal segments, rest MBF, stress MBF and MPR were significantly different across AIF sampling locations (p < 0.001). Stress MBF for the AoR (normal: 2.42 (2.15-2.84) mL/g/min; abnormal: 1.71 (1.28-1.98) mL/g/min) had the highest diagnostic accuracy (sensitivity 80 %, specificity 85 %, area under the curve 0.90; p < 0.001 versus stress MBF for all other locations including bLV: normal: 2.78 (2.39-3.14) mL/g/min; abnormal: 2.22 (1.83-2.48) mL/g/min; sensitivity 91 %, specificity 63 %, area under the curve 0.81) and performed better than MPR for the LV locations (p < 0.01). MPR for the AoR (normal: 2.43 (1.95-3.14); abnormal: 1.58 (1.34-1.90)) was not superior to MPR for the bLV (normal: 2.59 (2.04-3.20); abnormal: 1.69 (1.36-2.14); p = 0.717)., Conclusions: The AIF sampling location has a significant impact on MBF and MPR estimates by CMR perfusion, with AoR-based stress MBF comparing favorably to that for the current clinical reference bLV.

Aims: Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC., Methods and Results: Forty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischaemic preconditioning (RIPC, 3 cycles of 5 min leg ischaemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each intracoronary doxorubicin injections (0.45 mg/kg) given at Weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at Weeks 6, 8, 12, and 16, being sacrifice after that. In Study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed at week 6. In Study 1, left ventricular ejection fraction (LVEF) depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at Week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5 ± 9.1% vs. 32.5 ± 8.7%, P = 0.04). It was mainly due to conserved regional contractile function. In Study 2, transmission electron microscopy (TEM) at Week 6 showed fragmented mitochondria with severe morphological abnormalities in Untreated-Doxo pigs, together with upregulation of fission and autophagy proteins. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was less severe in RIPC+Doxo pigs., Conclusion: In a translatable large-animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from AIC early stages. RIPC is a promising intervention for testing in clinical trials in AIC., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: Magnetization transfer (MT) imaging exploits the interaction between bulk water protons and protons contained in macromolecules to induce signal changes through a special radiofrequency pulse. MT detects muscle damage in patients with neuromuscular conditions, such as limb-girdle muscular dystrophies or Charcot-Marie-Tooth disease, which are characterized by progressive fiber loss and replacement by fatty tissue. In Pompe disease, in which there is, in addition, an accumulation of glycogen inside the muscle fibers, MT has not been tested yet. Our aim is to estimate MT ratio (MTR) in the skeletal muscle of these patients and correlate it with intramuscular fat fraction (FF) and results of muscle function tests. Methods: We obtained two-point axial Dixon and Dixon-MT sequences of the right thigh on a 1.5 Teslas MRI scanner in 60 individuals, including 29 late onset Pompe disease patients, 2 patients with McArdle disease, and 29 age and sex matched healthy controls. FF and MTR were estimated. Muscle function using several muscle function tests, including quantification of muscle strength, timed test quality of life scales, conventional spirometry obtaining forced vital capacity while sitting and in the supine position, were assessed in all patients. Results: MTR was significantly lower in Pompe patients compared with controls (45.5 ± 8.5 vs. 51.7 ± 2.3, Student T -test, p < 0.05). There was a negative correlation between the MTR and FF muscles studied (correlation coefficient: -0.65, Spearman test: p < 0.05). MTR correlated with most of the muscle function test results. We analyzed if there was any difference in MTR values between Pompe patients and healthy controls in those muscles that did not have an increase in fat, a measure that could be related to the presence of glycogen in skeletal muscles, but we did not identify significant differences except in the adductor magnus muscle (48.4 ± 3.6 in Pompe vs. 51 ± 1.3 in healthy controls, Student T -test = 0.023). Conclusions: MTR is a sensitive tool to identify muscle loss in patients with Pompe disease and shows a good correlation with muscle function tests. Therefore, the MT technique can be useful in monitoring muscle degeneration in Pompe disease in clinical trials or natural history studies., Competing Interests: PM was employed by company Philips Healthcare Iberia. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nuñez-Peralta, Montesinos, Alonso-Jiménez, Alonso-Pérez, Reyes-Leiva, Sánchez-González, Llauger-Roselló, Segovia, Belmonte, Pedrosa, Martínez-Noguera, Matellini-Mosca, Walter and Díaz-Manera.)

Background: A small number of studies have confirmed the presence of oxidative damage in patients with Duchenne muscular dystrophy (DMD). Nevertheless, it is unknown if there a relationship of circulating markers of oxidative stress with a muscle injury., Objective: We evaluated if oxidative damage and anti-oxidant markers are associated with muscle damage in DMD., Methods: This cross-sectional study included 24 patients with DMD classified in ambulatory and non-ambulatory. Markers of muscle damage (creatine kinase [CK]), oxidative damage (malondialdehyde [MDA], and 8-isoprostane), anti-oxidant function (Thiol and mRNA of NRF2 and NF-κB) and nitric oxide (NO) were quantified in circulation., Results: Total NO, MDA, and 8-isoprostane concentrations were significantly (p < 0.05) higher, and thiol concentration was lower in non-ambulatory than ambulatory patients. A significant correlation (p < 0.05) between muscle injury (evaluated by Vignos scale) with CK (r = -0.382), NO (r = 0.444), MDA (r = 0.503), 8-isoprostanes (r = 0.435) and thiol (r = -0.430) was observed., Conclusion: These findings suggest that non-ambulatory have high oxidative damage and low anti-oxidant function than ambulatory patients with DMD. Total nitric oxide and oxidative damage plasma markers increase, but the anti-oxidant marker thiol decreases with a muscle injury in boys with DMD. The findings of this study suggest that these markers could be considered as goods indicators of oxidative damage in longitudinal studies to evaluate the muscle injury during DMD progression. Additionally, these findings add new information about the pathophysiology of DMD., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Significant increasing prevalences have been observed in gambling disorder (GD) in the last decades. This study analyzed the underlying mechanisms of the gambling severity with path analysis (implemented through Structural Equation Modeling, SEM), and assessed the potential moderator effect of the patients' sex. A sample of n = 512 treatment-seeking patients was assessed for sociodemographics and clinical state previously to the treatment. Results obtained in two separate SEM (for men and women) revealed differences in the direct effects and the mediational links. Among the male subsample, higher GD severity was directly related to the higher cognitive bias and the younger age of onset of the problematic gambling, while impulsivity levels and age of onset achieved an indirect effect on the disordered gambling mediated by the cognitive bias. Among females, GD severity was directly increased by younger age of onset, higher cognitive bias and lower self-directedness, while lower socioeconomic positions, and higher levels in harm avoidance achieved an indirect effect on the gambling severity mediated also by the distortions related to the gambling activity. These results provide new empirical evidence for a better understanding of the GD etiology, suggesting that the underlying complex links mediating the GD severity are strongly related to the patients' sex. The results can also contribute to design more effectiveness and precise therapy programs of patient-centered care.

The aim of the present study was to investigate the long-term impact of early intravenous metoprolol in ST-segment elevation myocardial infarction (STEMI) patients in terms of left ventricular (LV) strain with feature-tracking cardiovascular magnetic resonance (CMR) and its association with prognosis. A total of 270 patients with first anterior STEMI enrolled in the randomized METOCARD-CNIC clinical trial, assigned to receive up to 15 mg intravenous metoprolol before primary percutaneous coronary intervention versus conventional STEMI therapy, were included. LV global circumferential (GCS) and longitudinal (GLS) strain were assessed with feature-tracking CMR at 1 week after STEMI in 215 patients. The occurrence of major adverse cardiac events (MACE) at 5-year follow-up was the primary end point. Among 270 patients enrolled, 17 of 139 patients assigned to metoprolol arm and 31 of 131 patients assigned to control arm experienced MACE (hazard ratio [HR] 0.500, 95% confidence interval [CI] 0.277 to 0.903; p = 0.022). Impaired LV GCS and GLS strain were significantly associated with increased occurrence of MACE (GCS: HR 1.208, 95% CI 1.076 to 1.356, p =0.001; GLS: HR 1.362, 95% CI 1.180 to 1.573, p < 0.001). On multivariable analysis, LV GLS provided incremental prognostic value over late gadolinium enhancement (LGE) and LV ejection fraction (LVEF) (LGE + LVEF chi-square = 12.865, LGE + LVEF + GLS chi-square = 18.459; p =0.012). Patients with GLS ≥-11.5% (above median value) who received early intravenous metoprolol were 64% less likely to experience MACE than their counterparts with same degree of GLS impairment (HR 0.356, 95% CI 0.129 to 0.979; p = 0.045). In conclusion, early intravenous metoprolol has a long-term beneficial prognostic effect, particularly in patients with severely impaired LV systolic function. LV GLS with feature-tracking CMR early after percutaneous coronary intervention offers incremental prognostic value over conventional CMR parameters in risk stratification of STEMI patients., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular (LV) hypertrabeculation fulfilling noncompaction cardiomyopathy criteria has been detected in athletes. However, the association between LV noncompaction (LVNC) phenotype and vigorous physical activity (VPA) in the general population is disputed., Objectives: The aim of this study was to assess the relationship between LVNC phenotype on cardiac magnetic resonance (CMR) imaging and accelerometer-measured physical activity (PA) in a cohort of middle-aged nonathlete participants in the PESA (Progression of Early Subclinical Atherosclerosis) study., Methods: In PESA participants (n = 4,184 subjects free of cardiovascular disease), PA was measured by waist-secured accelerometers. CMR was performed in 705 subjects (mean age 48 ± 4 years, 16% women). VPA was recorded as total minutes per week. The study population was divided into 6 groups: no VPA and 5 sex-specific quintiles of VPA rate (Q1 to Q5). The Petersen criterion for LVNC was evaluated in all subjects undergoing CMR. For participants meeting this criterion (noncompacted-to-compacted ratio ≥2.3), 3 more restrictive LVNC criteria were also evaluated (Jacquier, Grothoff, and Stacey)., Results: LVNC phenotype prevalence according to the Petersen criterion was significantly higher among participants in the highest VPA quintile (Q5 = 30.5%) than in participants with no VPA (14.2%). The Jacquier and Grothoff criteria were also more frequently fulfilled in participants in the highest VPA quintile (Jacquier Q5 = 27.4% vs. no VPA = 12.8% and Grothoff Q5 = 15.8% vs. no VPA = 7.1%). The prevalence of the systolic Stacey LVNC criterion was low (3.6%) and did not differ significantly between no VPA and Q5., Conclusions: In a community-based study, VPA was associated with a higher prevalence of CMR-detected LVNC phenotype according to diverse established criteria. The association between VPA and LVNC phenotype was independent of LV volumes. According to these data, vigorous recreational PA should be considered as a possible but not uncommon determinant of LV hypertrabeculation in asymptomatic subjects., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Participation in gambling is rising in older adults. Indeed, in the coming years, engagement in gambling as a social activity is expected to increase more sharply in the elderly than in any other age group. Due to their exposure to powerful age-specific risk factors such as isolation, inactivity and failing health, older people are highly vulnerable to gambling-related problems. This study aimed to explore the existence of empirical clusters related to gambling habits in a sample of elderly participants from the general population. The sample included n = 361 participants, age range 50-90 years (mean 73.8, SD 8.4). Empirical clusters were identified through a two-step clustering analysis based on a broad set of indicators, including sociodemographic features, psychopathological state, substance use, life events, gambling preferences and scores on screening measures of gambling severity. The prevalence of GD in the study was 1.4%. Two clusters were identified: (a) cluster 1 (labeled as "low risk of gambling problems", n = 265, 73.4%), which included the higher proportion of non-gamblers or individuals who engage only in non-strategic gambling, women, widowed, and lower levels of education (no individual into this group met criteria for GD); and (b) cluster 2 (labeled as "higher risk of gambling problems", n = 96, 26.6%), which included the higher proportion of men, who reported both non-strategic and strategic gambling preferences (all participants diagnosed of GD were grouped into this cluster), older age, longer history of gambling, higher gambling severity, higher use of substances and worse psychopathological state. The elderly constitute a heterogeneous group with regard to gambling phenotypes. The results of this study may prove particularly useful for developing reliable screening tools able to identify older patients at a high risk of gambling problems, and for designing effective prevention and intervention programs.

Background: There are no studies based on a person-centered approach addressing sex-related differences in the characteristics of treatment-seeking patients with gambling disorder (GD). The main objective of the current study is to identify empirical clusters of GD based on several measures of the severity of gambling behavior, and considering the potential role of patient sex as a moderator., Methods: An agglomerative hierarchical clustering method was applied to an adult sample of 512 treatment-seeking patients (473 men and 39 women) by using a combination of the Schwarz Bayesian Information Criterion and log-likelihood function., Results: Three clusters were identified in the subsample of men: cluster M1 (low-mild gambling severity level, 9.1%), cluster M2 (moderate level, 60.9%), and cluster M3 (severe level, 30.0%). In the women subsample, two clusters emerged: cluster W1 (mild-moderate level, 64.1%), and cluster W2 (severe level, 35.9%). The most severe GD profiles were related to being single, multiple gambling preference for nonstrategic plus strategic games, early onset of the gambling activity, higher impulsivity levels, higher dysfunctional scores in the personality traits of harm avoidance, and self-directedness, and higher number of lifespan stressful life events (SLE). Differences between the empirical men and women clusters were found in different sociodemographic and clinical measurements., Conclusions: Men and women have distinct profiles regarding gambling severity that can be identified by a clustering approach. The sociodemographic and clinical characterization of each cluster by sex may help to establish specific preventive and treatment interventions.

Early metoprolol administration protects against myocardial ischemia-reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (total n = 122) underwent coronary artery occlusion of varying duration (20, 25, 30, 35, 40, 45, 50, or 60 min) followed by reperfusion. In each group, pigs were randomized to i.v. metoprolol (0.75 mg/kg) or vehicle (saline) 20 min after ischemia onset. The primary outcome measure was infarct size (IS) on day7 cardiac magnetic resonance (CMR) normalized to area at risk (AAR, measured by perfusion computed tomography [CT] during ischemia). Metoprolol treatment reduced overall mortality (10% vs 26%, p = 0.03) and the incidence and number of primary ventricular fibrillations during infarct induction. In controls, IS after 20-min ischemia was ≈ 5% of the area AAR. Thereafter, IS progressed exponentially, occupying almost all the AAR after 35 min of ischemia. Metoprolol injection significantly reduced the slope of IS progression (p = 0.004 for final IS). Head-to-head comparison (metoprolol treated vs vehicle treated) showed statistically significant reductions in IS at 30, 35, 40, and 50-min reperfusion. At 60-min reperfusion, IS was 100% of AAR in both groups. Despite more prolonged ischemia, metoprolol-treated pigs reperfused at 50 min had smaller infarcts than control pigs undergoing ischemia for 40 or 45 min and similar-sized infarcts to those undergoing 35-min ischemia. Day-45 LVEF was higher in metoprolol-treated vs vehicle-treated pigs (41.6% vs 36.5%, p = 0.008). In summary, metoprolol administration early during ischemia attenuates IS progression and reduces the incidence of primary ventricular fibrillation. These data identify metoprolol as an intervention ideally suited to the treatment of STEMI patients identified early in the course of infarction and requiring long transport times before primary angioplasty.

Background: Late-onset Pompe disease (LOPD) is a genetic disorder characterized by progressive degeneration of the skeletal muscles produced by a deficiency of the enzyme acid alpha-glucosidase. Enzymatic replacement therapy with recombinant human alpha-glucosidase seems to reduce the progression of the disease; although at the moment, it is not completely clear to what extent. Quantitative muscle magnetic resonance imaging (qMRI) is a good biomarker for the follow-up of fat replacement in neuromuscular disorders. The aim of this study was to describe the changes observed in fat replacement in skeletal muscles using qMRI in a cohort of LOPD patients followed prospectively., Methods: A total of 36 LOPD patients were seen once every year for 4 years. qMRI, several muscle function tests, spirometry, activities of daily living scales, and quality-of-life scales were performed on each visit. Muscle MRI consisted of two-point Dixon studies of the trunk and thigh muscles. Computer analysis of the images provided the percentage of muscle degenerated and replaced by fat in every muscle (known as fat fraction). Longitudinal analysis of the measures was performed using linear mixed models applying the Greenhouse-Geisser test., Results: We detected a statistically significant and continuous increase in mean thigh fat fraction both in treated (+5.8% in 3 years) and in pre-symptomatic patients (+2.6% in 3years) (Greenhouse-Geisser p < 0.05). As an average, fat fraction increased by 1.9% per year in treated patients, compared with 0.8% in pre-symptomatic patients. Fat fraction significantly increased in every muscle of the thighs. We observed a significant correlation between changes observed in fat fraction in qMRI and changes observed in the results of the muscle function tests performed. Moreover, we identified that muscle performance and mean thigh fat fraction at baseline visit were independent parameters influencing fat fraction progression over 4 years (analysis of covariance, p < 0.05)., Conclusions: Our study identifies that skeletal muscle fat fraction continues to increase in patients with LOPD despite the treatment with enzymatic replacement therapy. These results suggest that the process of muscle degeneration is not stopped by the treatment and could impact muscle function over the years. Hereby, we show that fat fraction along with muscle function tests can be considered a good outcome measures for clinical trials in LOPD patients., (© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: We aimed to evaluate the effect of early intravenous metoprolol treatment, microvascular obstruction (MVO), intramyocardial hemorrhage (IMH) and adverse left ventricular (LV) remodeling on the evolution of infarct and remote zone circumferential strain after acute anterior ST-segment elevation myocardial infarction (STEMI) with feature-tracking cardiovascular magnetic resonance (CMR)., Methods: A total of 191 patients with acute anterior STEMI enrolled in the METOCARD-CNIC randomized clinical trial were evaluated. LV infarct zone and remote zone circumferential strain were measured with feature-tracking CMR at 1 week and 6 months after STEMI., Results: In the overall population, the infarct zone circumferential strain significantly improved from 1 week to 6 months after STEMI (- 8.6 ± 9.0% to - 14.5 ± 8.0%; P < 0.001), while no changes in the remote zone strain were observed (- 19.5 ± 5.9% to - 19.2 ± 3.9%; P = 0.466). Patients who received early intravenous metoprolol had significantly more preserved infarct zone circumferential strain compared to the controls at 1 week (P = 0.038) and at 6 months (P = 0.033) after STEMI, while no differences in remote zone strain were observed. The infarct zone circumferential strain was significantly impaired in patients with MVO and IMH compared to those without (P < 0.001 at 1 week and 6 months), however it improved between both time points regardless of the presence of MVO or IMH (P < 0.001). In patients who developed adverse LV remodeling (defined as ≥ 20% increase in LV end-diastolic volume) remote zone circumferential strain worsened between 1 week and 6 months after STEMI (P = 0.036), while in the absence of adverse LV remodeling no significant changes in remote zone strain were observed., Conclusions: Regional LV circumferential strain with feature-tracking CMR allowed comprehensive evaluation of the sequelae of an acute STEMI treated with primary percutaneous coronary intervention and demonstrated long-lasting cardioprotective effects of early intravenous metoprolol., Trial Registration: ClinicalTrials.gov, NCT01311700. Registered 8 March 2011 - Retrospectively registered.

The use of instruments originally developed for measuring gambling activity in younger populations may not be appropriate in older age individuals. The aim of this study was to examine the presence of problematic and disordered gambling in seniors aged 50 or over, and study the reliability and validity properties of the SOGS (a screening measure to identify gambling related problems). Two independent samples were recruited: a clinical group of n = 47 patients seeking treatment at a Pathological Gambling Outpatient Unit, and a population-based group of n = 361 participants recruited from the same geographical area. Confirmatory factor analysis verified the bifactor structure for the SOGS with two correlated underlying dimensions [measuring the impact of gambling on the self primarily (Cronbach's alpha α = 0.87) or on both the self and others also (α = 0.82)], and a global dimension of gambling severity (also with excellent internal consistency, α = 0.90). The SOG obtained excellent accuracy/validity for identifying gambling severity based on the DSM-5 criteria (area under the ROC curve AUC = 0.97 for discriminating disordered gambling and AUC = 0.91 for discriminating problem gambling), and good convergent validity with external measures of gambling (Pearson's correlation R = 0.91 with the total number of DSM-5 criteria for gambling disorder, and R = 0.55 with the debts accumulated due to gambling) and psychopathology (R = 0.50, 0.43 and 0.44 with the SCL-90R depression, anxiety and GSI scales). The optimal cutoff point for identifying gambling disorder was 4 (sensitivity Se = 92.3% and specificity Sp = 98.6%) and 2 for identifying problem gambling (Se = 78.8% and Sp = 96.7%). This study provides empirical support for the reliability and validity of the SOGS for assessing problem gambling in elders, and identifies two specific factors that could help both research and clinical decision-making, based on the severity and consequences of the gambling activity., Competing Interests: The authors have declared that no competing interests exist.

Food addiction (FA) has been associated with greater psychopathology in individuals with eating disorders (ED) and obesity (OBE). The current study aims to provide a better phenotypic characterization of the FA construct by conducting a clustering analysis of FA in both conditions (ED and OBE). The total sample was comprised of 234 participants that scored positive on the Yale Food Addiction Scale 2.0. (YFAS-2) (119 bulimia nervosa (BN), 50 binge eating disorder (BED), 49 other specified feeding or eating disorder (OSFED) and 16 OBE). All participants completed a comprehensive battery of questionnaires. Three clusters of FA participants were identified. Cluster 1 (dysfunctional) was characterized by the highest prevalence of OSFED and BN, the highest ED severity and psychopathology, and more dysfunctional personality traits. Cluster 2 (moderate) showed a high prevalence of BN and BED and moderate levels of ED psychopathology. Finally, cluster 3 (adaptive) was characterized by a high prevalence of OBE and BED, low levels of ED psychopathology, and more functional personality traits. In conclusion, this study identified three distinct clusters of ED-OBE patients with FA and provides some insight into a better phenotypic characterization of the FA construct when considering psychopathology, personality and ED pathology. Future studies should address whether these three food addiction categories are indicative of therapy outcome.

Objectives: The study aimed to examine whether food addiction (FA) was associated with greater severity in both binge eating disorders (BED) and bulimia nervosa and, therefore, to determine if FA was predictive of treatment outcome., Method: Seventy-one adult patients with bulimia nervosa and BED (42 and 29, respectively) participated in the study. FA was assessed by means of the Yale Food Addiction Scale., Results: The results confirmed a high prevalence of FA in patients with binge disorders (around 87%) and also its association with a greater severity of the disorder (i.e., related to an increased eating psychopathology and greater frequency of binge eating episodes). Although FA did not appear as a predictor of treatment outcome in general terms, when the diagnostic subtypes were considered separately, FA was associated with poor prognosis in the BED group. In this vein, FA appeared as a mediator in the relationship between ED severity and treatment outcome., Discussions: Our findings suggest that FA may act as an indicator of ED severity, and it would be a predictor of treatment outcome in BED but not in BN., (© 2019 John Wiley & Sons, Ltd and Eating Disorders Association.)

Aims: Cardiac optical mapping is the gold standard for measuring complex electrophysiology in ex vivo heart preparations. However, new methods for optical mapping in vivo have been elusive. We aimed at developing and validating an experimental method for performing in vivo cardiac optical mapping in pig models., Methods and Results: First, we characterized ex vivo the excitation-ratiometric properties during pacing and ventricular fibrillation (VF) of two near-infrared voltage-sensitive dyes (di-4-ANBDQBS/di-4-ANEQ(F)PTEA) optimized for imaging blood-perfused tissue (n = 7). Then, optical-fibre recordings in Langendorff-perfused hearts demonstrated that ratiometry permits the recording of optical action potentials (APs) with minimal motion artefacts during contraction (n = 7). Ratiometric optical mapping ex vivo also showed that optical AP duration (APD) and conduction velocity (CV) measurements can be accurately obtained to test drug effects. Secondly, we developed a percutaneous dye-loading protocol in vivo to perform high-resolution ratiometric optical mapping of VF dynamics (motion minimal) using a high-speed camera system positioned above the epicardial surface of the exposed heart (n = 11). During pacing (motion substantial) we recorded ratiometric optical signals and activation via a 2D fibre array in contact with the epicardial surface (n = 7). Optical APs in vivo under general anaesthesia showed significantly faster CV [120 (63-138) cm/s vs. 51 (41-64) cm/s; P = 0.032] and a statistical trend to longer APD90 [242 (217-254) ms vs. 192 (182-233) ms; P = 0.095] compared with ex vivo measurements in the contracting heart. The average rate of signal-to-noise ratio (SNR) decay of di-4-ANEQ(F)PTEA in vivo was 0.0671 ± 0.0090 min-1. However, reloading with di-4-ANEQ(F)PTEA fully recovered the initial SNR. Finally, toxicity studies (n = 12) showed that coronary dye injection did not generate systemic nor cardiac damage, although di-4-ANBDQBS injection induced transient hypotension, which was not observed with di-4-ANEQ(F)PTEA., Conclusions: In vivo optical mapping using voltage ratiometry of near-infrared dyes enables high-resolution cardiac electrophysiology in translational pig models., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To estimate trajectories of the gambling disorder (GD) severity for 12 months following a manualized cognitive-behavior-therapy (CBT) program, and to identify the main variables associated with each trajectory., Methods: Latent Class Growth Analysis examined the longitudinal changes of n = 603 treatment-seeking patients with GD., Results: Five separate empirical trajectories were identified: T1 (n = 383, 63.5%) was characterized by the most highest baseline gambling severity levels and positive progress to recovery during the follow-up period; T2 (n = 154, 25.5%) featured participants with high baseline gambling severity and good progress to recovery; T3 (n = 30, 5.0%) was made up of patients with high gambling baseline severity and slow progress to recovery; T4 (n = 13, 2.2%) and T5 (n = 23, 3.8%) contained participants with high baseline gambling severity and moderate (T4) and poor (T5) progress in GD severity during the follow-up. Psychopathological state and personality traits discriminated between trajectories. Poor compliance with the therapy guidelines and the presence of relapses also differed between the trajectories., Conclusions: Our findings show that patients seeking treatment for GD are heterogeneous and that trends in progress following treatment can be identified considering sociodemographic features, psychopathological state and personality traits. These results could be useful in developing more efficient interventions for GD patients., (Copyright © 2019. Published by Elsevier Masson SAS.)

After a reperfused myocardial infarction (MI), dynamic tissue changes occur (edema, inflammation, microvascular obstruction, hemorrhage, cardiomyocyte necrosis, and ultimately replacement by fibrosis). The extension and magnitude of these changes contribute to long-term prognosis after MI. Cardiac magnetic resonance (CMR) is the gold-standard technique for noninvasive myocardial tissue characterization. CMR is also the preferred methodology for the identification of potential benefits associated with new cardioprotective strategies both in experimental and clinical trials. However, there is a wide heterogeneity in CMR methodologies used in experimental and clinical trials, including time of post-MI scan, acquisition protocols, and, more importantly, selection of endpoints. There is a need for standardization of these methodologies to improve the translation into a real clinical benefit. The main objective of this scientific expert panel consensus document is to provide recommendations for CMR endpoint selection in experimental and clinical trials based on pathophysiology and its association with hard outcomes., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to evaluate the effect of early intravenous metoprolol on left ventricular (LV) strain assessed with feature-tracking cardiovascular magnetic resonance (CMR)., Background: Early intravenous metoprolol before primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) portends better outcomes in the METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial., Methods: A total of 197 patients with acute anterior STEMI who were enrolled in the METOCARD-CNIC trial (100 allocated to intravenous metoprolol before primary PCI and 97 control patients) were evaluated. LV global circumferential strain (GCS) and global longitudinal strain (GLS) were measured with feature-tracking CMR at 1 week and 6 months after STEMI and compared between randomization groups., Results: Patients who received early intravenous metoprolol had significantly more preserved LV strain compared with the control patients at 1 week after STEMI (GCS -13.9 ± 3.8% vs. -12.6 ± 3.9%, respectively; p = 0.013; GLS -11.9 ± 2.8% vs. -10.9 ± 3.2%, respectively; p = 0.032). In both groups, LV strain significantly improved during follow-up (mean difference between 6-month and 1-week strain for the metoprolol group: GCS -2.9%, 95% confidence interval [CI]: -3.5% to -2.4%; GLS: -2.9%, 95% CI: -3.4% to -2.4%; both p < 0.001; the control group: GCS -3.4%, 95% CI: -3.9% to -2.8%; GLS -3.4%, 95% CI: -3.9% to -3.0%; both p < 0.001). When dividing the overall cohort of patients in quartiles of GCS and GLS, there were significantly fewer patients in the first quartile (i.e., the worst LV systolic function) who received early intravenous metoprolol compared with control patients at 1 week and 6 months (p < 0.05 for GCS and GLS at both time points)., Conclusions: In patients with anterior STEMI, early administration of intravenous metoprolol before primary PCI was associated with significantly fewer patients with severely depressed LV GCS and GLS, both at 1 week and 6 months. Feature-tracking CMR represents a complementary tool to evaluate the benefits of cardioprotective therapies. (Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion [METOCARD-CNIC]: NCT01311700)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Myocardial infarction (MI) alters cardiac fibre organization with unknown consequences on ventricular arrhythmia. We used diffusion tensor imaging (DTI) of three-dimensional (3D) cardiac fibres and scar reconstructions to identify the main parameters associated with ventricular arrhythmia inducibility and ventricular tachycardia (VT) features after MI., Methods and Results: Twelve pigs with established MI and three controls underwent invasive electrophysiological characterization of ventricular arrhythmia inducibility and VT features. Animal-specific 3D scar and myocardial fibre distribution were obtained from ex vivo high-resolution contrast-enhanced T1 mapping and DTI sequences. Diffusion tensor imaging-derived parameters significantly different between healthy and scarring myocardium, scar volumes, and left ventricular ejection fraction (LVEF) were included for arrhythmia risk stratification and correlation analyses with VT features. Ventricular fibrillation (VF) was the only inducible arrhythmia in 4 out of 12 infarcted pigs and all controls. Ventricular tachycardia was also inducible in the remaining eight pigs during programmed ventricular stimulation. A DTI-based 3D fibre disorganization index (FDI) showed higher disorganization within dense scar regions of VF-only inducible pigs compared with VT inducible animals (FDI: 0.36; 0.36-0.37 vs. 0.32; 0.26-0.33, respectively, P = 0.0485). Ventricular fibrillation induction required lower programmed stimulation aggressiveness in VF-only inducible pigs than VT inducible and control animals. Neither LVEF nor scar volumes differentiated between VF and VT inducible animals. Re-entrant VT circuits were localized within areas of highly disorganized fibres. Moreover, the FDI within heterogeneous scar regions was associated with the median VT cycle length per animal (R2 = 0.5320)., Conclusion: The amount of scar-related cardiac fibre disorganization in DTI sequences is a promising approach for ventricular arrhythmia stratification after MI., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Atherosclerosis is a chronic inflammatory disease, but data on arterial inflammation at early stages is limited., Objectives: The purpose of this study was to characterize vascular inflammation by hybrid 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI)., Methods: Carotid, aortic, and ilio-femoral 18 F-FDG PET/MRI was performed in 755 individuals (age 40 to 54 years; 83.7% men) with known plaques detected by 2-/3-dimensional vascular ultrasound and/or coronary calcification in the PESA (Progression of Early Subclinical Atherosclerosis) study. The authors evaluated the presence, distribution, and number of arterial inflammatory foci (increased 18 F-FDG uptake) and plaques with or without inflammation (coincident 18 F-FDG uptake)., Results: Arterial inflammation was present in 48.2% of individuals (24.4% femorals, 19.3% aorta, 15.8% carotids, and 9.3% iliacs) and plaques in 90.1% (73.9% femorals, 55.8% iliacs, and 53.1% carotids). 18 F-FDG arterial uptakes and plaques significantly increased with cardiovascular risk factors (p < 0.01). Coincident 18 F-FDG uptakes were present in 287 of 2,605 (11%) plaques, and most uptakes were detected in plaque-free arterial segments (459 of 746; 61.5%). Plaque burden, defined by plaque presence, number, and volume, was significantly higher in individuals with arterial inflammation than in those without (p < 0.01). The number of plaques and 18 F-FDG uptakes showed a positive albeit weak correlation (r = 0.25; p < 0.001)., Conclusions: Arterial inflammation is highly prevalent in middle-aged individuals with known subclinical atherosclerosis. Large-scale multiterritorial PET/MRI allows characterization of atherosclerosis-related arterial inflammation and demonstrates 18 F-FDG uptake in plaque-free arterial segments and, less frequently, within plaques. These findings suggest an arterial inflammatory state at early stages of atherosclerosis. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder for which no cure exists. The disease is characterized by premature aging and inevitable death in adolescence due to cardiovascular complications. Most HGPS patients carry a heterozygous de novo LMNA c.1824C > T mutation, which provokes the expression of a dominant-negative mutant protein called progerin. Therapies proven effective in HGPS-like mouse models have yielded only modest benefit in HGPS clinical trials. To overcome the gap between HGPS mouse models and patients, we have generated by CRISPR-Cas9 gene editing the first large animal model for HGPS, a knockin heterozygous LMNA c.1824C > T Yucatan minipig. Like HGPS patients, HGPS minipigs endogenously co-express progerin and normal lamin A/C, and exhibit severe growth retardation, lipodystrophy, skin and bone alterations, cardiovascular disease, and die around puberty. Remarkably, the HGPS minipigs recapitulate critical cardiovascular alterations seen in patients, such as left ventricular diastolic dysfunction, altered cardiac electrical activity, and loss of vascular smooth muscle cells. Our analysis also revealed reduced myocardial perfusion due to microvascular damage and myocardial interstitial fibrosis, previously undescribed readouts potentially useful for monitoring disease progression in patients. The HGPS minipigs provide an appropriate preclinical model in which to test human-size interventional devices and optimize candidate therapies before advancing to clinical trials, thus accelerating the development of effective applications for HGPS patients., Competing Interests: The authors declare that they have no conflict of interest.After acceptance of this article, the authors have generated new HGPS minipigs by SCNT using heterozygous LMNA 1824 C>T Yucatan minipig fibroblasts (in collaboration with Dr. Eckhard Wolf, Ludwig-Maximilians-Universität München, Germany).

Background: Anthracycline-induced cardiotoxicity is a major clinical problem, and early cardiotoxicity markers are needed., Objectives: The purpose of this study was to identify early doxorubicin-induced cardiotoxicity by serial multiparametric cardiac magnetic resonance (CMR) and its pathological correlates in a large animal model., Methods: Twenty pigs were included. Of these, 5 received 5 biweekly intracoronary doxorubicin doses (0.45 mg/kg/injection) and were followed until sacrifice at 16 weeks. Another 5 pigs received 3 biweekly doxorubicin doses and were followed to 16 weeks. A third group was sacrificed after the third dose. All groups underwent weekly CMR examinations including anatomical and T 2 and T 1 mapping (including extracellular volume [ECV] quantification). A control group was sacrificed after the initial CMR., Results: The earliest doxorubicin-cardiotoxicity CMR parameter was T 2 relaxation-time prolongation at week 6 (2 weeks after the third dose). T 1 mapping, ECV, and left ventricular (LV) motion were unaffected. At this early time point, isolated T 2 prolongation correlated with intracardiomyocyte edema secondary to vacuolization without extracellular space expansion. Subsequent development of T 1 mapping and ECV abnormalities coincided with LV motion defects: LV ejection fraction declined from week 10 (2 weeks after the fifth and final doxorubicin dose). Stopping doxorubicin therapy upon detection of T 2 prolongation halted progression to LV motion deterioration and resolved intracardiomyocyte vacuolization, demonstrating that early T 2 prolongation occurs at a reversible disease stage., Conclusions: T 2 mapping during treatment identifies intracardiomyocyte edema generation as the earliest marker of anthracycline-induced cardiotoxicity, in the absence of T 1 mapping, ECV, or LV motion defects. The occurrence of these changes at a reversible disease stage shows the clinical potential of this CMR marker for tailored anthracycline therapy., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Difficulties in emotion regulation (ER) are common in females with eating disorders (ED). However, no study to date has analyzed ER in males with ED. In the study at hand, we assessed ER in males with ED and compared results to both females with ED and healthy controls (HC). We also examined associations between ER difficulties, personality, and psychopathology. A total of 62 males with ED were compared with 656 females with ED, as well as 78 male and 286 female HC. ER was assessed by means of the Difficulties in Emotion Regulation Scale (DERS). We found that males and females with ED showed greater ER difficulties compared to HC. Pronounced general psychopathology was a shared factor associated with higher ER difficulties in both males and females with ED. However, whereas higher novelty seeking, higher cooperativeness, lower reward dependence, and lower self-directedness were related to higher ER difficulties in females with ED, lower persistence was associated with ER difficulties in males with ED. In sum, males and females with ED show similar ER difficulties, yet they are distinct in how ER deficits relate to specific personality traits. Research on strategies promoting ER in the treatment of males with ED is warranted.

Introduction: Colorectal cancer (CRC) is a major health concern and it is associated with significant morbidity and mortality. Over the last decades, the relationship between cancer and nutritional and inflammatory status in oncologic patients was studied thoroughly and multiple immunonutritional scores were developed. These scores have been mainly related to the prognosis of several cancers. An interaction between the tumour and the host is generated, triggering a systemic inflammatory reaction leading to several neuroendocrine changes. This situation favours a tendency towards anorexia and catabolism. Our hypothesis is that nutritional and inflammatory status of oncologic patients is correlated to postoperative morbidity., Methods: This is a prospective observational cohort study with those patients undergoing curative surgery for CRC at our institution between September 2015 and March 2017. Nutritional and inflammatory status was established using Onodera's Prognostic Nutritional Index (PNI). Complications (overall, severe, infectious and anastomotic leakage) were carefully collected during the first 30 days of the postoperative period., Results: After carrying out the multivariate analysis, PNI turned out to be a great predictive and protective factor for overall complications (RR: 0.279; 95% CI: 0.141-0.552), severe complications (RR: 0.355; 95% CI: 0.130-0.965), infectious complications (RR: 0.220; 95% CI: 0.099-0.489) and anastomotic leakage (RR: 0.151; 95% CI: 0.036-0.640)., Conclusion: Our work reports that PNI is an independent predictive factor for the development of postoperative complications following curative surgery for CRC., (Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.)

There is scarce evidence for pulmonary artery denervation (PADN) as a potential treatment for chronic postcapillary pulmonary hypertension (PH). We aimed to perform a proof-of-concept of PADN in a translational model of chronic PH. Nineteen pigs with chronic postcapillary PH (secondary to pulmonary vein banding) were randomized to surgical-PADN (using bipolar radiofrequency clamps) or sham procedure. Additionally, 6 healthy animals underwent percutaneous-PADN to compare the pulmonary artery (PA) lesion generated with both approaches. In the surgical-PADN arm, hemodynamic evaluation and cardiac magnetic resonance (CMR) were performed at baseline and at 2 and 3-month follow-up. Histological assessment was carried out at the completion of the protocol. Eighteen pigs (6 following surgical-PADN, 6 sham and 6 percutaneous-PADN) completed the protocol. A complete transmural PA lesion was demonstrated using surgical clamps, whereas only focal damage to adventitial fibers was observed after percutaneous-PADN. In the surgical-PADN arm, the hemodynamic profile did not significantly differ between groups neither at baseline [mean pulmonary artery pressure (mPAP) median values of 32.0 vs. 27.5 mmHg, P = 0.394 and indexed pulmonary vascular resistance (iPVR) 5.9 vs. 4.7 WU m 2 , P = 0.394 for PADN/sham groups, respectively] nor at any follow-up (mPAP of 35.0 vs. 35.0 mmHg, P = 0.236 and iPVR of 8.3 vs. 6.7 WU m 2 , P = 0.477 at third month in PADN/sham groups, respectively). Surgical-PADN was not associated with any benefit in RV anatomy or function on CMR/histology. In a large-animal model of chronic postcapillary PH, transmural PADN with surgical clamps was associated with a neutral pulmonary hemodynamic effect.

Synthetic cathinones are a type of drug belonging to group of new psychoactive substances (NPSs). The illicit market for these substances is characterized by the continuous introduction to the market of new analogs to evade legislation and to avoid detection. New screening and confirmation assays are therefore needed, mainly in forensic/clinical samples. In the current development, a porous membrane-protected, micro-solid-phase extraction (μ-SPE) has been developed for the assessment of several cathinones in urine. The μ-SPE device consisted of a cone-shaped polypropylene (PP) porous membrane containing the adsorbent (molecularly imprinted polymers, MIPs, synthesized for the first time for this class of drugs). MIPs were prepared using ethylone and 3-methylmethcathinone (3-MMC) as templates, ethylene glycol dimethacrylate (EGDMA) as a functional monomer, divinylbenzene (DVB) as a cross-linker, and 2,2´-azobisisobutyronitrile (AIBN) as an initiator. The prepared ethylone-based MIP and 3-MMC-based MIP have been fully characterized and evaluated as new selective adsorbents for μ-SPE. Cathinones separation/determination was performed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Optimum loading conditions (pH 5.0, loading for 4.0 minutes under orbital-horizontal shaking at 200 rpm) and elution conditions [2.0 mL of 75:20:5 heptane/2-propanol/ammonium hydroxide and ultrasounds assistance (37 kHz, 325 W) for 4.0 minutes] were found for ethylone-based MIP. Validation (intra-day and inter-day precision and analytical recovery) showed RSD values lower than 9 and 10% for intra-day and inter-day precision, and within the 88%-101% range for intra-day and inter-day analytical recovery., (© 2018 John Wiley & Sons, Ltd.)