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Preventable psychosocial suffering is an unmet need in patients with cancer around the world, significantly compromising quality of life and impairing cancer health outcomes. This narrative review overviews the global prevalence of emotional distress and cancer-related needs and the access barriers to psychosocial care. The COVID-19 pandemic has served only to amplify the need for psychosocial care, exacerbating the inadequacy of available psychosocial resources, particularly in low- and middle-income countries. Proposed solutions include implementing routine screening for emotional distress, addressing stigma related to mental health needs, and increased attention to the psychosocial dimensions of cancer care in oncology training and interprofessional models of care. There is an urgent need to address health policy issues such as resource allocation in cancer control plans and to embrace technological innovation in order to fill the universal gaps to providing more equitable psychosocial cancer care., Funding: None., Competing Interests: WR has grant funding from the NCI/NIH Comprehensive Cancer Center and Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program. WL is the President of the International Psycho-oncology Society. ML the Medical Director for the Canadian Association of Psychosocial Oncology and has received travel support from the Lancet Oncology Commission on the Human Crisis of Cancer.1 All other authors declare no competing interests., (© 2024 The Author(s).)

Humans tend to give more weight to information confirming their beliefs than to information that disconfirms them. Nevertheless, this apparent irrationality has been shown to improve individual decision-making under uncertainty. However, little is known about this bias' impact on decision-making in a social context. Here, we investigate the conditions under which confirmation bias is beneficial or detrimental to decision-making under social influence. To do so, we develop a Collective Asymmetric Reinforcement Learning (CARL) model in which artificial agents observe others' actions and rewards, and update this information asymmetrically. We use agent-based simulations to study how confirmation bias affects collective performance on a two-armed bandit task, and how resource scarcity, group size and bias strength modulate this effect. We find that a confirmation bias benefits group learning across a wide range of resource-scarcity conditions. Moreover, we discover that, past a critical bias strength, resource abundance favors the emergence of two different performance regimes, one of which is suboptimal. In addition, we find that this regime bifurcation comes with polarization in small groups of agents. Overall, our results suggest the existence of an optimal, moderate level of confirmation bias for decision-making in a social context., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bergerot et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The global cancer burden is rising, particularly in low- and middle-income countries (LMIC), highlighting a critical research gap in understanding disparities in supportive care access. To address this, the Multinational Association of Supportive Care in Cancer (MASCC) Health Disparities Committee initiated a global survey to investigate and delineate these disparities. This study aims to explore and compare supportive care access disparities between LMIC and High-Income Countries (HIC)., Methods: An online cross-sectional survey was conducted among active members of MASCC. Members, representing diverse healthcare professions received email invitations. The survey, available for 3 weeks, comprised sections covering (1) sociodemographic information; (2) clinical service/practice-related disparities in their region/nation; (3) population groups facing disparities within their region or country. Chi-squared or Fisher's exact test for cross-sectional analyses, and a multivariable logistic regression model was employed for statistical analysis., Results: A total of 218 active members participated, with one-quarter (26.6%) from LMIC and 18.4% ethnic minorities, timely cancer care (43.7%) and timely supportive care (45.0%) emerged as the most pressing disparities globally. Notably, participants from LMIC underscored cancer drug affordability (56.4%) and supportive care guideline implementation (56.4%) as critical issues. Economically disadvantaged populations were noted as more likely to face disparities by both LMIC and HIC (non-US-based) respondents, while US-based respondents identified racial/ethnic minorities as facing more disparities., Conclusion: This global survey reveals significant disparities in cancer supportive care between LMIC and HIC, with a particular emphasis on medication affordability and guideline implementation in LMIC. Addressing these disparities requires targeted intervention, considering specific regional priorities., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Breast cancer survival rates have shown notable improvements over the years thanks to advancements in detection, treatment modalities, and supportive care. However, survivors often encounter challenges when reintegrating into daily life and managing persistent physical and psychological concerns. This review article aims to delve into the multifaceted emotional complexities faced by survivors, encompassing a spectrum of issues from fear of recurrence to body image insecurities, thus emphasizing the imperative for comprehensive support. Articles were reviewed through searches of PubMed and through searches of the author's own file. We will examine not only the risk factors contributing to heightened psychological distress but also the periods of vulnerability and the most common unmet needs encountered by these individuals. Additionally, we will discuss various psychological interventions and strategies designed to promote resilience and enhance the quality of life post-diagnosis. Furthermore, we will underscore the pressing need for ongoing, specific research endeavors aimed at addressing the long-term psychological impacts of cancer recurrence on survivorship. By shedding light on these critical aspects, we aim not only to provide insight into the challenges faced by survivors but also to advocate for the importance of integrating comprehensive psychological support into survivorship care. Through this thorough exploration, we seek to empower both survivors and healthcare professionals alike, facilitating a deeper understanding of the complexities inherent in the breast cancer survivorship journey. Ultimately, our aim is to highlight the crucial aspects that must be considered by healthcare professionals in providing holistic care to breast cancer survivors.

Background: Left ventricular thrombus (LVT) is a source of cardiogenic embolic stroke. Conflicting data exist in the literature regarding the utilization of intravenous thrombolysis (IVT) at the acute phase of stroke in presence of LVT. We sought to assess the efficacy and safety of reperfusion therapies (IVT and/or thrombectomy) in patients with LVT., Methods: We retrospectively analyzed patients with acute ischemic stroke and proven LVT and divided them in two groups: an intervention group with patients treated by reperfusion therapies and a control group with untreated patients., Results: Between 2009 and 2021, 3890 patients were treated by reperfusion therapies in the Lyon stroke center, 33 of whom (0.9%) had LVT. We identified 27 control patients. There were more embolic recurrences at six months in the intervention group than in the control group (nine recurrences versus three, P=0.03, OR=13.56, 95% CI [1.5;195]). Only two early embolic recurrences (< 24h) occurred, both in the IVT group. There was a 4.8-fold decrease in the median NIHSS score between baseline and 24h follow-up in the intervention group (P<0.0001), and the two groups exhibited similar six-month mortality. At stroke onset, cardiopathy was known in 70% of patients, while LVT was known in 30%., Conclusion: Acute reperfusion therapies seem to be effective in the context of stroke in patients with LVT. However, further studies are needed to support the hypothesis that stroke recurrence might be related to the use of IVT., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Type 2 diabetes (T2D) is a frequent comorbidity encountered in patients with severe aortic stenosis (AS), leading to an adverse left ventricular (LV) remodeling and dysfunction. Metabolic alterations have been suggested as contributors of the deleterious effect of T2D on LV remodeling and function in patients with severe AS, but so far, the underlying mechanisms remain unclear. Mitochondria play a central role in the regulation of cardiac energy metabolism., Objectives: We aimed to explore the mitochondrial alterations associated with the deleterious effect of T2D on LV remodeling and function in patients with AS, preserved ejection fraction, and no additional heart disease., Methods: We combined an in-depth clinical, biological and echocardiography phenotype of patients with severe AS, with (n = 34) or without (n = 50) T2D, referred for a valve replacement, with transcriptomic and histological analyses of an intra-operative myocardial LV biopsy., Results: T2D patients had similar AS severity but displayed worse cardiac remodeling, systolic and diastolic function than non-diabetics. RNAseq analysis identified 1029 significantly differentially expressed genes. Functional enrichment analysis revealed several T2D-specific upregulated pathways despite comorbidity adjustment, gathering regulation of inflammation, extracellular matrix organization, endothelial function/angiogenesis, and adaptation to cardiac hypertrophy. Downregulated gene sets independently associated with T2D were related to mitochondrial respiratory chain organization/function and mitochondrial organization. Generation of causal networks suggested a reduced Ca 2+ signaling up to the mitochondria, with the measured gene remodeling of the mitochondrial Ca 2+ uniporter in favor of enhanced uptake. Histological analyses supported a greater cardiomyocyte hypertrophy and a decreased proximity between the mitochondrial VDAC porin and the reticular IP3-receptor in T2D., Conclusions: Our data support a crucial role for mitochondrial Ca 2+ signaling in T2D-induced cardiac dysfunction in severe AS patients, from a structural reticulum-mitochondria Ca 2+ uncoupling to a mitochondrial gene remodeling. Thus, our findings open a new therapeutic avenue to be tested in animal models and further human cardiac biopsies in order to propose new treatments for T2D patients suffering from AS., Trial Registration: URL: https://www., Clinicaltrials: gov ; Unique Identifier: NCT01862237., (© 2024. The Author(s).)

Purpose: The study aims to explore unmet social needs and sources of financial toxicities in patients as noted by health care professionals and researchers in cancer supportive care, shedding light on potential health disparities., Methods: In this cross-sectional survey, we anonymously surveyed active members of the Multinational Association of Supportive Care in Cancer (MASCC). The survey, structured in three sections, included questions regarding the routine assessment of social needs during patient consultations, sociodemographic aspects, factors influencing financial toxicity (FT), perceived support for managing FT, and available/desirable resources., Results: A total of 218 MASCC members were included, predominantly from high-income countries (HIC, 73.4%), with many age 41-60 years (56.5%) and female (56.9%). Drug/treatment cost and insurance coverage were the main sources for FT among the HIC, whereas participants from low-middle-income countries (LMIC) considered transportation cost, loss of employment because of cancer diagnosis, and unavailability of return-to-work services as the top three sources of FT. Respondents from LMIC (adjusted odds ratio [aOR], 3.01 [95% CI, 1.15 to 7.93]) and physicians (aOR, 2.67 [95% CI, 1.15 to 6.21]) were more likely to routinely assess financial coverages. Socioeconomic status was consistently ranked as one of the top three sources of financial toxicities by participants from LMIC (34%), HIC excluding the United States (38%), those who do not self-identify as racial/ethnic minority (36%), and physicians (40%)., Conclusion: This global survey of health care professionals and researchers in HIC and LMIC revealed varying approaches to assessing financial coverage and social needs. Socioeconomic status emerged as a consistent concern across countries, affecting financial toxicities. The study highlights the need for tailored approaches and improved resource visibility while emphasizing clinicians' pivotal role in addressing financial aspects of cancer care.

The integration of palliative care into routine oncology practice is the standard of care by most leading cancer organizations. Palliative medicine helps to deliver higher quality of care at a lower cost. However, there are barriers to implementing palliative oncology at many institutions for myriad reasons. In this article, we discuss an innovative strategy that ASCO implemented called the Communities of Practice (CoP). We share our experiences as the Palliative Care CoP and how our group seeks to develop processes and structures to collectively promote systemic change and enhance palliative care delivery for people with cancer. Our Palliative Care CoP engages with senior leaders, administrators, and those in power to achieve a shared vision of delivering holistic health care for people with serious illness. We continue to evolve to meet our members' growing needs by addressing eight main domains: (1) increasing palliative care education and resources; (2) creating opportunities for global palliative care research; (3) providing peer mentorship and community building; (4) engaging with patient advocates; (5) supporting and developing interdisciplinary teams; (6) assisting with professional development and identity formation, especially for trainees and early career faculty; (7) extending our outreach through social media; and (8) enhancing the clinical practice of palliative oncology. The ASCO CoP has been a vital forum to realize ASCO's mission of conquering cancer and advancing the Art and Science of Cancer Care: From Comfort to Cure.

While the positive impact of early palliative care on the quality of life of cancer patients is well established, there is a noticeable research gap in developing countries. This study sought to determine the impact of an outpatient palliative care (OPC) program on the location of death among patients in Brazil. This was a retrospective study including patients with cancer who died between January 2022 and December 2022 in 32 private cancer centers in Brazil. Data were collected from medical records, encompassing demographics, cancer characteristics, and participation in the OPC program. The study involved 1980 patients, of which 32.3% were in the OPC program. OPC patients were predominantly younger (average age at death of 66.8 vs. 68.0 years old, p = 0.039) and composed of women (59.4% vs. 51.3%, p = 0.019) compared to the no-OPC patients. OPC patients had more home/hospice deaths (19.6% vs. 10.4%, p < 0.001), and participation in the outpatient palliative care program strongly predicted home death (OR: 2.02, 95% CI: 1.54-2.64). Our findings suggest a significant impact of the OPC program on increasing home and hospice deaths among patients with cancer in our sample. These findings emphasize the potential of specialized OPC programs to enhance end-of-life care, particularly in low-resource countries facing challenges related to social and cultural dimensions of care and healthcare access.

Equity, diversity, and inclusion (EDI) are essential for healthcare organizations since they allow for the development of programs and initiatives that bring together diverse perspectives and knowledge. Global multidisciplinary organizations, such as the Multinational Association for Supportive Care in Cancer (MASCC), need to understand the perspective of their members regarding EDI to identify opportunities to enhance diversity and inclusiveness and to better meet the needs of members from different backgrounds and resources. The MASCC Health Disparities Committee designed a survey to identify issues related to disparities faced by MASCC members when providing supportive care to patients with cancer and to examine the EDI landscape within the organization. Here, we report results related to EDI initiatives within the organization. Two-hundred and eighteen MASCC members responded to the survey (response rate 10.2%). The results indicated that respondents were generally satisfied with how MASCC manages leadership, membership, and organization-related EDI issues. Opportunities for improvement noted by respondents included developing strategies to foster a more diverse membership, improving communication regarding diversity in the organization, and increasing EDI content in educational sessions and publications. The results of this survey represent the first attempt at understanding how to improve EDI within MASCC and will be utilized to guide further initiatives and programs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Women are more likely to develop heart failure (HF) after myocardial infarction. However, diagnosis and reperfusion are often delayed., Objectives: To compare the prevalence of HF after primary percutaneous coronary intervention (PPCI)-treated ST segment myocardial infarction (STEMI) between sexes and to study its associations with comorbidities, infarct size, and left ventricular (LV) systolic and diastolic dysfunctions (DD)., Methods: The patients with PPCI-treated anterior STEMI, from the CIRCUS study cohort, were followed up for 1 year and HF events were recorded. Evaluation of ejection fraction (LVEF) and DD were performed at baseline and at 1 year. The elevated LV filling pressure (LVFP) included Grades 2 and 3 DD., Results: Of the 791 patients from the CIRCUS study, 135 were women. At 1 year, the proportion of patients who developed HF was 21% among men and 34% among women ( p  = 0.001). In the subset of 407 patients with available diastolic parameters, the rate of HF was also higher in women. HF during the initial hospitalization was comparable between the sexes. However, women had a higher incidence of rehospitalization for HF within the first year after STEMI (14.1% vs. 4.1%, p  = 0.005). Women were older with a higher prevalence of hypertension. The infarct size and LVEF were similar between the sexes. Elevated LVFP was observed more frequently in women than in men during the initial hospitalization and at 1 year (26% vs. 12%, p  = 0.04, and 22% vs. 12%, p  = 0.006, respectively). Interestingly, only initial elevated LVFP (HR 5.9, 95% CI: 2.4-14.5, p  < 0.001), age, and hypertension were independently associated with rehospitalization for HF., Conclusions: After PPCI-treated anterior STEMI, despite comparable infarct size and LVEF, women presented a higher proportion of rehospitalization for HF than men. That was likely due to a greater DD associated with older age and hypertension., Competing Interests: The 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., (© 2024 Leboube, Camboulives, Bochaton, Amaz, Bergerot, Altman, Loppinet, Cherpaz, Monsec, Sportouch, Trinh, Soulier, Bernard, Derumeaux, Mewton, Ovize and Thibault.)

Objectives: To evaluate the prevalence of intra-myocardial fatty scars (IMFS) most likely indicating previous silent myocardial infarction (SMI), as detected on coronary artery calcium (CAC) computed tomography (CT) scans in diabetic patients without history of coronary heart disease (CHD)., Methods: Diabetic patients screened for silent coronary insufficiency in a tertiary-care, university hospital between Jan-2015 and Dec-2016 were categorized according to their CAC score in two groups comprising 242 patients with CACS = 0 and 145 patients with CACS ≥ 300. CAC-CT scans were retrospectively evaluated for subendorcardial and transmural IMFS of the left ventricle. Adipose remodeling, patients' characteristics, cardiovascular risk factors and metabolic profile were compared between groups., Results: Eighty-three (21%) patients with IMFS were identified, 55 (37.9%) in the group CACS ≥ 300 and 28 (11.6%) in the CACS = 0 (OR = 4.67; 95% CI = 2.78-7.84; p < 0.001). Total and average surface of IMFS and their number per patient were similar in both groups (p = 0.55; p = 0.29; p = 0.61, respectively). In the group CACS ≥ 300, patients with IMFS were older (p = 0.03) and had longer-lasting diabetes (p = 0.04). Patients with IMFS were older and had longer history of diabetes, reduced glomerular filtration rate, more coronary calcifications (all p < 0.05), and higher prevalence of carotid plaques (OR = 3.03; 95% CI = 1.43-6.39, p = 0.004). After correction for other variables, only a CACS ≥ 300 (OR = 5.12; 95% CI = 2.66-9.85; p < 0.001) was associated with an increased risk of having IMFS., Conclusions: In diabetic patients without known CHD, IMFSs were found in patients without coronary calcifications, although not as frequently as in patients with heavily calcified coronary arteries. It remains to be established if this marker translates in an upwards cardiovascular risk restratification especially in diabetic patients with CACS = 0., Clinical Relevance Statement: In diabetic patients without history of coronary heart disease, intramyocardial fatty scars, presumably of post-infarction origin, can be detected on coronary artery calcium CT scans more frequently, but not exclusively, if the coronary arteries are heavily calcified as compared to those without calcifications., Key Points: • Intramyocardial fatty scars (IMFS), presumably of post-infarction origin, can be detected on coronary artery calcium (CAC) CT scans more frequently, but not exclusively, in diabetic patients with CACS ≥ 300 as compared to patients CACS = 0. • Patients with IMFS were older and had longer history of diabetes, reduced glomerular filtration rate, and more coronary calcifications. • Carotid plaques and CACS ≥ 300 were associated with an increased risk of having IMFS, about three and five folds respectively., (© 2023. The Author(s).)

Purpose: To update the ASCO guideline (2018) on the practical assessment and management of age-associated vulnerabilities in older patients undergoing systemic cancer therapy., Methods: An Expert Panel conducted a systematic review to identify relevant randomized clinical trials (RCTs), systematic reviews, and meta-analyses from January 2016 to December 2022., Results: A total of 26 publications met eligibility criteria and form the evidentiary basis for the update., Recommendations: The Expert Panel reiterates its overarching recommendation from the prior guideline that geriatric assessment (GA), including all essential domains, should be used to identify vulnerabilities or impairments that are not routinely captured in oncology assessments for all patients over 65 years old with cancer. Based on recently published RCTs demonstrating significantly improved clinical outcomes, all older adults with cancer (65+ years old) receiving systemic therapy with GA-identified deficits should have GA-guided management (GAM) included in their care plan. GAM includes using GA findings to inform cancer treatment decision-making as well as to address impairments through appropriate interventions, counseling, and/or referrals. A GA should include high priority aging-related domains known to be associated with outcomes in older adults with cancer: physical and cognitive function, emotional health, comorbid conditions, polypharmacy, nutrition, and social support. Clinical adaptation of the GA based on patient population, resources, and time is appropriate.The Panel recommends the Practical Geriatric Assessment as one option for this purpose (https://old-prod.asco.org/sites/new-www.asco.org/files/content-files/practice-patients/documents/2023-PGA-Final.pdf; https://youtu.be/jnaQIjOz2Dw; https://youtu.be/nZXtwaGh0Z0).Additional information is available at www.asco.org/supportive-care-guidelines.

Despite the importance of chemotherapy-associated adverse events in oncology practice and the broad range of interventions available to mitigate them, limited systematic efforts have been made to identify, critically appraise and summarize the totality of evidence on the effectiveness of these interventions. Herein, we review the most common long-term (continued beyond treatment) and late or delayed (following treatment) adverse events associated with chemotherapy and other anticancer treatments that pose major threats in terms of survival, quality of life and continuation of optimal therapy. These adverse effects often emerge during and continue beyond the course of therapy or arise among survivors in the months and years following treatment. For each of these adverse effects, we discuss and critically evaluate their underlying biological mechanisms, the most commonly used pharmacological and non-pharmacological treatment strategies, and evidence-based clinical practice guidelines for their appropriate management. Furthermore, we discuss risk factors and validated risk-assessment tools for identifying patients most likely to be harmed by chemotherapy and potentially benefit from effective interventions. Finally, we highlight promising emerging supportive-care opportunities for the ever-increasing number of cancer survivors at continuing risk of adverse treatment effects., (© 2023. Springer Nature Limited.)

Objectives: Telehealth for mental healthcare expanded rapidly with the COVID-19 pandemic's onset; however, global access disparities emerged. Telehealth challenges and opportunities for Latino cancer patients from different geographical regions must be explored., Methods: A cross-sectional online survey (March-July 2021) of mental health providers, serving Latino cancer patients in Latin America, United States, and Spain, contained close-ended questions related to the use of telehealth during the pandemic and open-ended questions on recommending/not recommending telehealth., Results: In a sample of 148 providers from 21 countries, 60.5% reported that at least some of their patients had difficulties with Internet speed and connectivity and lacked knowledge about using electronic devices (43.2%) or the Internet (45.4%). Lacking privacy at home (66.0%) and childcare (26.0%) were reported patient challenges. Internet connectivity or speed were issues for providers (43.2%) themselves. Improving patient reach was a reported telehealth benefit (64.2%). Geographical access (43.2%) and physical limitations (35.8%) were considerations in offering telehealth. Considerations for not recommending telehealth were patient age (24.3%) and lacking technological knowledge (29.1%)., Conclusions: Telehealth for mental healthcare may improve patient access issues caused by geographical and transportation conditions and patient functionality. Findings provide insight into telehealth benefits and challenges in Latino patient populations. Future studies should examine patient access and use by region., (© 2023 John Wiley & Sons Ltd.)

Aims: To describe the outcomes and associated factors in a population of patients admitted to emergency departments with at least one condition of oxygen supply/demand imbalance, regardless of the troponin result or restrictive criteria for type 2 myocardial infarction., Methods: We constituted a retrospective cohort of 824 patients. Medical records of patients having undergone a troponin assay were reviewed for selection and classification, and data including in-hospital stay and readmissions were collected. The reported outcomes are in-hospital mortality, 3-year mortality, and major adverse cardiovascular events., Results: Patients with myocardial infarction or injury, either chronic or acute, were older, with more history of hypertension and chronic heart or renal failure but not for other cardiovascular risk factors and medical history. Acute myocardial injury and type 2 myocardial infarction were significantly associated with in-hospital mortality [odds ratio (OR) 3.71 95% confidence interval (CI) 1.90-7.33 and OR 3.15 95% CI 1.59-6.28, respectively]. However, the long-term mortality does not differ in comparison with patients presenting chronic myocardial injury or nonelevated troponin, ranging from 26.9 to 34.3%. Patients with chronic myocardial injury and type 2 myocardial infarction had more long-term major cardiovascular events (39.3 and 38.8%), but only for acute heart failure, and none was associated with this outcome after adjustment., Conclusion: Among patients admitted to emergency departments with an oxygen supply/demand imbalance, acute myocardial injury and type 2 myocardial infarction are strongly associated with in-hospital mortality. However, they are not associated with higher long-term mortality or major cardiovascular events after discharge, which tend to occur in elderly people with comorbidities., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Seeking and consuming nutrients is essential to survival and the maintenance of life. Dynamic and volatile environments require that animals learn complex behavioral strategies to obtain the necessary nutritive substances. While this has been classically viewed in terms of homeostatic regulation, recent theoretical work proposed that such strategies result from reinforcement learning processes. This theory proposed that phasic dopamine (DA) signals play a key role in signaling potentially need-fulfilling outcomes. To examine links between homeostatic and reinforcement learning processes, we focus on sodium appetite as sodium depletion triggers state- and taste-dependent changes in behavior and DA signaling evoked by sodium-related stimuli. We find that both the behavior and the dynamics of DA signaling underlying sodium appetite can be accounted for by a homeostatically regulated reinforcement learning framework (HRRL). We first optimized HRRL-based agents to sodium-seeking behavior measured in rodents. Agents successfully reproduced the state and the taste dependence of behavioral responding for sodium as well as for lithium and potassium salts. We then showed that these same agents account for the regulation of DA signals evoked by sodium tastants in a taste- and state-dependent manner. Our models quantitatively describe how DA signals evoked by sodium decrease with satiety and increase with deprivation. Lastly, our HRRL agents assigned equal preference for sodium versus the lithium containing salts, accounting for similar behavioral and neurophysiological observations in rodents. We propose that animals use orosensory signals as predictors of the internal impact of the consumed good and our results pose clear targets for future experiments. In sum, this work suggests that appetite-driven behavior may be driven by reinforcement learning mechanisms that are dynamically tuned by homeostatic need., Competing Interests: The authors declare no conflict of interest.

Background: Preserving health-related quality of life (HRQOL) is an important goal during renal cell carcinoma treatment. We report HRQOL outcomes from a phase II trial (NCT03173560)., Patients and Methods: HRQOL data were collected during a multicenter, randomized, open-label phase II study comparing the safety and efficacy of 2 different starting doses of lenvatinib (18 mg vs. 14 mg daily) in combination with everolimus (5 mg daily), following one prior vascular endothelial growth factor-targeted treatment. HRQOL was measured using 3 different instruments-FKSI-DRS, EORTC QLQ-C30, and EQ-5D-3L-which were all secondary endpoints. Change from baseline was assessed using linear mixed-effects models. Deterioration events for time to deterioration (TTD) analyses were defined using established thresholds for minimally important differences in the change from baseline for each scale. TTD for each treatment arm was estimated using the Kaplan-Meier method., Results: Baseline characteristics of the 343 participants randomly assigned to 18 mg lenvatinib (n = 171) and 14 mg lenvatinib (n = 172) were well balanced. Least-squares mean estimates for change from baseline were favorable for the 18 mg group over the 14 mg group for the FKSI-DRS and most EORTC QLQ-C30 scales, but differences between treatments did not exceed the minimally important thresholds. Median TTD was longer among participants in the 18 mg group than those in the 14 mg group for most scales., Conclusions: Participants who received an 18 mg lenvatinib starting dose had favorable HRQOL scores and longer TTD on most scales compared with those who received a 14 mg starting dose., (© The Author(s) 2022. Published by Oxford University Press.)

Background Spatial resolution, soft-tissue contrast, and dose-efficient capabilities of photon-counting CT (PCCT) potentially allow a better quality and diagnostic confidence of coronary CT angiography (CCTA) in comparison to conventional CT. Purpose To compare the quality of CCTA scans obtained with a clinical prototype PCCT system and an energy-integrating detector (EID) dual-layer CT (DLCT) system. Materials and Methods In this prospective board-approved study with informed consent, participants with coronary artery disease underwent retrospective electrocardiographically gated CCTA with both systems after injection of 65-75 mL of 400 mg/mL iodinated contrast agent at 5 mL/sec. A prior phantom task-based quality assessment of the detectability index of coronary lesions was performed. Ultra-high-resolution parameters were used for PCCT (1024 matrix, 0.25-mm section thickness) and EID DLCT (512 matrix, 0.67-mm section thickness). Three cardiac radiologists independently performed a blinded analysis using a five-point quality score (1 = insufficient, 5 = excellent) for overall image quality, diagnostic confidence, and diagnostic quality of calcifications, stents, and noncalcified plaques. A logistic regression model, adjusted for radiologists, was used to evaluate the proportion of improvement in scores with the best method. Results Fourteen consecutive participants (12 men; mean age, 61 years ± 17) were enrolled. Scores of overall quality and diagnostic confidence were higher with PCCT images with a median of 5 (interquartile range [IQR], 2) and 5 (IQR, 1) versus 4 (IQR, 1) and 4 (IQR, 3) with EID DLCT images, using a mean tube current of 255 mAs ± 0 versus 349 mAs ± 111 for EID DLCT images ( P < .01). Proportions of improvement with PCCT images for quality of calcification, stent, and noncalcified plaque were 100%, 92% (95% CI: 71, 98), and 45% (95% CI: 28, 63), respectively. In the phantom study, detectability indexes were 2.3-fold higher for lumen and 2.9-fold higher for noncalcified plaques with PCCT images. Conclusion Coronary CT angiography with a photon-counting CT system demonstrated in humans an improved image quality and diagnostic confidence compared with an energy-integrating dual-layer CT. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Sandfort and Bluemke in this issue.

Objectives: The aim of this study is to compare the image quality of in vivo coronary stents between an energy integrating detectors dual-layer computed tomography (EID-DLCT) and a clinical prototype of spectral photon counting computed tomography (SPCCT)., Materials and Methods: In January to June 2021, consecutive patients with coronary stents were prospectively enrolled to undergo a coronary computed tomography (CT) with an EID-DLCT (IQon, Philips) and an SPCCT (Philips). The study was approved by the local ethical committee and patients signed an informed consent. A retrospectively electrocardiogram-gated acquisition was performed with optimized matching parameters on the 2 scanners (EID-DLCT: collimation, 64 × 0.625 mm; kVp, 120, automatic exposure control with target current at 255 mAs; rotation time, 0.27 seconds; SPCCT: collimation, 64 × 0.275 mm; kVp, 120; mAs, 255; rotation time, 0.33 seconds). The injection protocol was the same on both scanners: 65 to 75 mL of Iomeron (Bracco) at 5 mL/s. Images were reconstructed with slice thickness of 0.67 mm, 512 matrix, XCB (Xres cardiac standard) and XCD (Xres cardiac detailed) kernel, iDose 3 for EID-DLCT and 0.25-mm slice thickness, 1024 matrix, Detailed 2 and Sharp kernel, and iDose 6 for SPCCT. Two experienced observers measured the proximal and distal external and internal diameters of the stents to quantify blooming artifacts. Regions of interest were drawn in the lumen of the stent and of the upstream coronary artery. The difference (Δ S-C) between the respective attenuation values was calculated as a quantification of stent-induced artifacts on intrastent image quality. For subjective image quality, 3 experienced observers graded with a 4-point scale the image quality of different parameters: coronary wall before the stent, stent lumen, stent structure, calcifications surrounding the stent, and beam-hardening artifacts., Results: Eight patients (age, 68 years [interquartile range, 8]; all men; body mass index, 26.2 kg/m2 [interquartile range, 4.2]) with 16 stents were scanned. Five stents were not evaluable owing to motion artifacts on the SPCCT. Of the remaining, all were drug eluting stents, of which 6 were platinum-chromium, 3 were cobalt-platinum-iridium, and 1 was stainless steel. For 1 stent, no information could be retrieved. Radiation dose was lower with the SPCCT (fixed CT dose index of 25.7 mGy for SPCCT vs median CT dose index of 35.7 [IQ = 13.6] mGy; P = 0.02). For 1 stent, the internal diameter was not assessable on EID-DLCT. External diameters were smaller and internal diameters were larger with SPCCT (all P < 0.05). Consequently, blooming artifacts were reduced on SPCCT (P < 0.05). Whereas Hounsfield unit values within the coronary arteries on the 2 scanners were similar, the Δ S-C was lower for SPCCT-Sharp as compared with EID-DLCT-XCD and SPCCT-Detailed 2 (P < 0.05). The SPCCT received higher subjective scores than EID-DLCT for stent lumen, stent structure, surrounding calcifications and beam-hardening for both Detailed 2 and Sharp (all P ≤ 0.05). The SPCCT-Sharp was judged better for stent structure and beam-hardening assessment as compared with SPCCT-Detailed 2., Conclusion: Spectral photon counting CT demonstrated improved objective and subjective image quality as compared with EID-DLCT for the evaluation of coronary stents even with a reduced radiation dose., Competing Interests: Conflicts of interest and sources of funding: European Union Horizon 2020 research and innovation program under grant agreement no. 668142., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Aging is a risk factor for type 2 myocardial infarction or myocardial injury, but few data are available on the elderly. We aimed to determine the factors associated with these pathologies and mortality in the elderly population and its age classes., Methods: A retrospective cohort of all patients with oxygen mismatch (anemia, hypoxia, tachycardia, hypo/hypertension) for whom a troponin drawn was performed at admission in 2 emergency departments. Medical records were reviewed and classified as having type 2 myocardial infarction, acute or chronic myocardial injury, or no myocardial injury., Results: Of the 824 patients who presented with oxygen mismatch, 675 (81.9%) were older than 65 years. Age over 85 years was a risk factor for acute non-ischemic myocardial injury (odds ratio, 95% confidence interval 2.23, 1.34-3.73). Non-ischemic myocardial injury was associated with hypoxemia, tachycardia, and acute renal failure in those older than 85 years, but only with acute infection in the 75-84-year-old group. Type 2 myocardial infarction was associated only with acute renal failure in the oldest group and, in the 75-84-year-old group, with acute heart failure and shock. Patients older than 85 years with acute myocardial injury, with or without infarction, had a higher in-hospital mortality, but subsequently, mortality depends more on the comorbidities than on age., Conclusion: Factors associated with type 2 myocardial infarction and acute non-ischemic myocardial injury in elderly admitted with oxygen mismatch vary notably between age classes. They are associated with in-hospital mortality but not with subsequent mortality when other cormorbities are taken into account., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid (LBPA), is a phospholipid specifically enriched in the late endosome-lysosome compartment playing a crucial role for the fate of endocytosed components. Due to its presence in extracellular fluids during diseases associated with endolysosomal dysfunction, it is considered as a possible biomarker of disorders such as genetic lysosomal storage diseases and cationic amphiphilic drug-induced phospholipidosis. However, there is no true validation of this biomarker in human studies, nor a clear identification of the carrier of this endolysosome-specific lipid in biofluids. The present study demonstrates that in absence of any sign of renal failure, BMP, especially all docosahexaenoyl containing species, are significantly increased in the urine of patients treated with the antiarrhythmic drug amiodarone. Such urinary BMP increase could reflect a generalized drug-induced perturbation of the endolysosome compartment as observed in vitro with amiodarone-treated human macrophages. Noteworthy, BMP was associated with extracellular vesicles (EVs) isolated from human urines and extracellular medium of human embryonic kidney HEK293 cells and co-localizing with classical EV protein markers CD63 and ALIX. In the context of drug-induced endolysosomal dysfunction, increased BMP-rich EV release could be useful to remove excess of undigested material. This first human pilot study not only reveals BMP as a urinary biomarker of amiodarone-induced endolysosomal dysfunction, but also highlights its utility to prove the endosomal origin of EVs, also named as exosomes. This peculiar lipid already known as a canonical late endosome-lysosome marker, may be thus considered as a new lipid marker of urinary exosomes., Competing Interests: Declaration of competing interest The authors declared no competing financial interest., (Copyright © 2020 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Background: Postinfarction adverse left ventricular (LV) remodelling is strongly associated with heart failure events. Conicity index, sphericity index and LV global functional index (LVGFI) are new LV remodelling indexes assessed by cardiac magnetic resonance (CMR)., Aim: To assess the predictive value of the new indexes for 1-year adverse LV remodelling in patients with anterior ST-segment elevated myocardial infarction (STEMI)., Methods: CMR studies were performed in 129 patients with anterior STEMI (58±12 years; 78% men) from the randomized CIRCUS trial (CMR substudy) treated with primary percutaneous coronary intervention and followed for the occurrence of major adverse cardiovascular events (MACE) (death or hospitalization for heart failure). Conicity index, sphericity index, LVGFI, infarct size and microvascular obstruction (MVO) were assessed by CMR performed 5±4 days after coronary reperfusion. Adverse LV remodelling was defined as an increase in LV end-diastolic volume of ≥15% by transthoracic echocardiography at 1 year., Results: Adverse LV remodelling occurred in 27% of patients at 1 year. Infarct size and MVO were significantly predictive of adverse LV remodelling: odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05 (P<0.001) and OR 1.12, 95% CI 1.05-1.22 (P<0.001), respectively. Among the newly tested indexes, only LVGFI was significantly predictive of adverse LV remodelling (OR 1.10, 95% CI 1.03-1.16; P=0.001). In multivariable analysis, infarct size remained an independent predictor of adverse LV remodelling at 1 year (OR 1.05, 95% CI 1.02-1.08; P<0.001). LVGFI and infarct size were associated with occurrence of MACE: OR 1.21, 95% CI 1.08-1.37 (P<0.001) and OR 1.02, 95% CI 1.00-1.04 (P=0.018), respectively. Conicity and sphericity indexes were not associated with MACE., Conclusions: LVGFI was associated with adverse LV remodelling and MACE 1 year after anterior STEMI., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: Recent publications suggest that left atrial (LA) myopathy is a potential source of thromboembolism, independent of atrial fibrillation., Aims: We sought to investigate whether the presence of atrial premature activity after an ischaemic stroke is associated with LA remodelling and dysfunction, and might be a surrogate marker of LA myopathy., Methods: After an ischaemic stroke or a transient ischaemic attack, patients without known atrial fibrillation or overt heart disease were included prospectively in the study. All patients had a standard workup, including ambulatory Holter electrocardiogram monitoring and transthoracic echocardiography. In some patients, transoesophageal echocardiography was also performed. Anatomical and functional LA remodelling were assessed using minimal and maximal volumes and LA emptying fraction in two-dimensional and three-dimensional echocardiography. Patients were separated into two groups according to the burden of atrial premature complexes (APCs), measured by Holter electrocardiography., Results: Among 148 eligible patients recruited from October 2015 to May 2016, 93 were included in the group with non-frequent APCs (nf-APC:<100 APCs/24hours) and 43 in the group with frequent APCs (f-APC:>100 APCs/24hours). Twelve patients had paroxysmal atrial fibrillation, and were not included in the statistical analysis. Maximal and minimal indexed LA volumes were significantly higher in the f-APC group than in the nf-APC group (P<0.01). LA emptying fraction was worse in the f-APC group than in the nf-APC group. In addition, LA appendage emptying velocity was impaired in the f-APC group, and was correlated with LA remodelling variables, especially LA emptying fraction (r=0.621)., Conclusions: After an ischaemic stroke or a transient ischaemic attack, excessive APCs are associated with LA remodelling. Thus, LA dilatation and dysfunction reflect early LA myopathy, which might itself be responsible for cardioembolic stroke., (Copyright © 2020. Published by Elsevier Masson SAS.)

Despite promising experimental studies and encouraging proof-of-concept clinical trials, interventions aimed at limiting infarct size have failed to improve clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). Our objective was to examine whether variables (cardiovascular risk factors, comorbidities, post-procedural variables, cotreatments) might be associated with clinical outcomes in STEMI patients independently from infarct size reduction. The present study was based on a post hoc analysis of the CIRCUS trial database (Clinicaltrials.gov NCT01502774) that assessed the clinical benefit of a single intravenous bolus of cyclosporine in 969 patients with anterior STEMI. Since cyclosporine had no detectable effect on clinical outcomes as well as on any measured variable, we here considered the whole study population as one group. Multivariate analysis was performed to address the respective weight of infarct size and variables in clinical outcomes. Multivariate analysis revealed that several variables (including gender, hypertension, renal dysfunction, TIMI flow grade post-PCI < 3, and treatment administered after PCI with betablockers and angiotensin-converting enzyme inhibitors) had per se a significant influence on the occurrence of [death or hospitalization for heart failure] at 1 year. The relative weight of infarct size and variables on the composite endpoint of [death or hospitalization for heart failure] at 1 year was 18% and 82%, respectively. Several variables contribute strongly to the clinical outcomes of STEMI patients suggesting that cardioprotective strategy might not only focus on infarct size reduction.

Hereditary hemorrhagic telangiectasia is a rare vascular genetic disease. Epistaxis is the most frequent and disabling manifestation, and timolol appears to be a new therapeutic option as non-selective beta-blockers have in vitro and in vivo anti-angiogenic properties. Our main objective was to evaluate the efficacy of TIMOLOL nasal spray as a treatment for epistaxis in hereditary hemorrhagic telangiectasia. This study is a single-center, randomized, phase 2, double-blind placebo-controlled study with an allocation ratio of 1:1. It was proposed to patients with hereditary hemorrhagic telangiectasia monitored at the French Reference Center, and we included patients aged over 18 years, diagnosed with hereditary hemorrhagic telangiectasia and epistaxis. The treatment was self-administered by the patient with a posology of one spray (50 µL) of timolol 0.5% or placebo in each nostril twice a day for 28 consecutive days. The primary efficacy endpoint was mean monthly epistaxis duration, assessed by monitoring epistaxis grids. A total of 58 patients were randomized and treated. The baseline characteristics were similar in the 2 groups. Mean monthly epistaxis duration measured at 3 months was not significantly different in the 26 patients receiving the drug in comparison with the placebo group (p = 0.54). Toxicity was low and no severe adverse events were reported. One limitation is that we included all HHT patients with nosebleeds and did not take into account history of nasal surgery or nasal crusts. Timolol, administered by nasal spray at a dose of 0.25 mg in each nostril twice a day for 28 consecutive days, did not improve epistaxis in patients with hereditary hemorrhagic telangiectasia at 4 months after the beginning of the treatment.

Aims: Diastolic dysfunction is frequent in patients with type 2 diabetes mellitus (DM2) and associated with a poor prognosis. This study aimed to describe diastolic function changes over time in DM2 patients and to identify predictive factors of diastolic function deterioration., Methods and Results: Diastolic function was assessed by echocardiography according to the EACVI/ASE recommendations at baseline and 3-year follow-up in a prospective cohort of 310 DM2 patients without overt heart disease. Predictors of diastolic function deterioration were identified using logistic regression analysis. During the 3-year follow-up, prevalence of diastolic dysfunction increased from 49% to 67% (P = 0.001). Only 32% of the patients had a normal diastolic function both at baseline and 3 years and 27% of the patients presented diastolic function deterioration. At multivariable analysis, age (OR = 1.05 [1.01-1.09], P < 0.01), retinopathy (OR = 2.00 [1.10-3.63], P = 0.02), and increase in systolic blood pressure during follow-up (OR = 1.03 [1.01-1.04], P < 0.01) were predictive of diastolic function deterioration., Conclusion: Age, retinopathy, and increase in blood pressure over time are associated with an increased risk of diastolic function deterioration in DM2 patients. The presence of these co-factors might help to early identify patients at risk of heart failure., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: Type 2 diabetes mellitus (T2DM) may alter cardiac structure and function, but obesity, hypertension (HTN), or aging can induce similar abnormalities., Objectives: This study sought to link cardiac phenotypes in T2DM patients with clinical profiles and outcomes using cluster analysis., Methods: Baseline echocardiography and a composite endpoint (cardiovascular mortality and hospitalization) were evaluated in 842 T2DM patients from 2 prospective cohorts. A cluster analysis was performed on echocardiographic variables, and the association between clusters and clinical profiles and outcomes was assessed., Results: Three clusters were identified. Cluster 1 patients had the lowest left ventricular (LV) mass index and ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e') ratio, had the highest left ventricular ejection fraction (LVEF), and were predominantly male with the lowest rate of obesity or HTN. Cluster 2 patients had the highest strain and highest E/e' ratio, were the oldest, were predominantly female, and had the lowest rate of isolated T2DM (without HTN or obesity). Cluster 3 patients had the highest LV mass index and volumes and the lowest LVEF and strain, were predominantly male, and shared similar age and rate of obesity and HTN as cluster 1 patients. After follow-up of 67 months (interquartile range: 40 to 87), the composite endpoint occurred in 56 of 521 patients (10.8%). Clusters 2 (hazard ratio: 2.37; 95% confidence interval: 1.15 to 4.88) and 3 (hazard ratio: 2.19; 95% confidence interval: 1.00 to 4.82) had a similar outcome, which was worse than cluster 1., Conclusions: Cluster analysis of echocardiographic variables identified 3 different echocardiographic phenotypes of T2DM patients that were associated with distinct clinical profiles and highlighted the prognostic value of LV remodeling and subclinical dysfunction., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Paroxysmal atrial fibrillation (PAF) is common, often silent, and can be difficult to detect. Echocardiographic parameters assessing left atrial (LA) remodelling correlated with atrial fibrosis in permanent AF, but less is known about earlier stages such as PAF. We aimed to evaluate whether 2D and 3D echocardiographic (2DE and 3DE) assessment of LA anatomy and function is able to identify patients with PAF., Methods and Results: This case-control study included 102 patients without overt heart disease, 44 patients with PAF. Anatomical remodelling was assessed using indexed maximal, minimal, and pre-atrial contraction volumes. Reservoir, conduit, and pump functions were assessed by volume and strain methods. All parameters were assessed by 2DE and 3DE and were compared between the two groups. Receiver-operating characteristic curves were constructed for each parameter for PAF prediction. PAF patients had bigger LA volumes than non-PAF group. Using 3DE, all atrial functions were impaired in the PAF group, regardless of the parameters used (all P < 0.05), whereas using 2DE, conduit function did not reach significant difference. Areas under the curve (AUCs) for 3D parameters were higher than those for equivalent 2DE parameters. PAF was best predicted by LA minimal indexed volume assessed by 2DE or 3DE (AUC 0.82 and 0.86, respectively) and 3D-LA ejection fraction and area strain (AUC = 0.82 and 0.81, respectively)., Conclusion: Anatomical and functional LA remodelling assessed by 2DE and 3DE is independently and strongly associated with PAF, suggesting that these parameters can help identify PAF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling., Methods: In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume., Results: A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups., Conclusions: In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).