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Improvement in cancer therapy has led to an increasing number of cancer survivors, some of whom may suffer from the cardiotoxic effects of chemotherapy. Cardiomyopathy can occur years after completion of the chemotherapy and it is important to recognize this early, as complete recovery of cardiac function is possible in some cases. In this article we will review chemotherapy-induced cardiomyopathy and discuss its treatment options. [ABSTRACT FROM AUTHOR]

The purpose of this study was to report our clinical experience with image-guided drainage of pericardial effusions in oncology patients. IRB approval was obtained for this retrospective, HIPAA-compliant study. From November 2002 to January 2008, 40 patients underwent 43 image-guided drainages of pericardial effusions. The medical records were reviewed to analyze the technical aspects of the procedures, complications, and clinical outcomes. Thirty-three pericardial drains were placed and 10 pericardiocenteses were performed. The technical success rate was 100%. Thirty-three procedures were performed under computed tomographic (CT) guidance, five under ultrasound (US) guidance, and five using both CT and US guidance. There were no technical, procedure-related complications. Delayed postprocedure complications and arrhythmias occurred in 11 cases, for an overall complication rate of 25.6%. All complications occurred in patients who had undergone drain placement. Nine patients developed new or worsening arrhythmias and six of these patients required transfer to a higher level of care or the initiation of pharmacological management. In 58.6% of drain placements, including 4 of 11 patients who developed complications, the catheter could have been removed earlier. The median overall survival was 6.47 months (95% CI: 2.37, 12.7). In conclusion, image-guided pericardial drain placement is safe and feasible. Due to the frequency of delayed postprocedure arrhythmias, follow-up monitoring in a telemetry unit is recommended. Prompt catheter removal after drainage may reduce the incidence of delayed post-catheter-insertion arrhythmias. [ABSTRACT FROM AUTHOR]

In humans, the eye pupils respond to both physical light sensed by the retina and mental representations of light produced by the brain. Notably, our pupils constrict when a visual stimulus is illusorily perceived brighter, even if retinal illumination is constant. However, it remains unclear whether such perceptual penetrability of pupil responses is an epiphenomenon unique to humans or whether it represents an adaptive mechanism shared with other animals to anticipate variations in retinal illumination between successive eye fixations. To address this issue, we measured the pupil responses of both humans and macaque monkeys exposed to three chromatic versions (cyan, magenta, and yellow) of the Asahi brightness illusion. We found that the stimuli illusorily perceived brighter or darker trigger differential pupil responses that are very similar in macaques and human participants. Additionally, we show that this phenomenon exhibits an analogous cyan bias in both primate species. Beyond evincing the macaque monkey as a relevant model to study the perceptual penetrability of pupil responses, our results suggest that this phenomenon is tuned to ecological conditions because the exposure to a "bright cyan-bluish sky" may be associated with increased risks of dazzle and retinal damages.

An observer willing to cross a street must first estimate if the approaching cars offer enough time to safely complete the task. The brain areas supporting this perception, known as Time-To-Contact (TTC) perception, have been mainly studied through noninvasive correlational approaches. We carried out an experiment in which patients were tested during an awake brain surgery electrostimulation mapping to examine the causal implication of various brain areas in the street-crossing decision process. Forty patients were tested in a gap acceptance task before their surgery to establish a baseline performance. The task was individually adapted upon this baseline level and carried out during their surgery. We acquired and normalized to MNI space the coordinates of the functional areas that influenced task performance. A total of 103 stimulation sites were tested, allowing to establish a large map of the areas involved in the street-crossing decision. Multiple sites were found to impact the gap acceptance decision. A direct implication was however found mostly for sites within the right parietal lobe, while indirect implication was found for sites within the language, motor, or attentional networks. The right parietal lobe can be considered as causally influencing the gap acceptance decision. Other positive sites were all accompanied with dysfunction in other cognitive functions, and therefore should probably not be considered as the site of TTC estimation., (© 2023 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Objectives: Pulmonary hypertension (PH) is an important physiologic variable in the assessment of patients undergoing major thoracic operations but all too often neglected because of the need for right heart catheterization (RHC) due to the inaccuracy of transthoracic echocardiography. Patients with lung cancer often require endobronchial ultrasound (EBUS) as part of the staging of the cancer. We sought to investigate whether EBUS can be used to screen these patients for PH., Methods: Patients undergoing a major thoracic operation requiring EBUS for staging were included prospectively in the study. All patients had also a RHC (gold standard). We aimed to compare the pulmonary artery pressure measurements by EBUS with the RHC values., Results: A total of 20 patients were enrolled in the study. The prevalence of abnormal pulmonary artery pressure was 65% based on RHC. All patients underwent measurement of the pulmonary vascular acceleration time (PVAT) by EBUS with no adverse events. Linear regression analysis comparing PVAT and RHC showed a correlation (r = -0.059, -0.010 to -0.018, P  = .007). A receiver operator characteristic curve (area under the curve = 0.736) was used to find the optimal PVAT threshold (140 milliseconds) to predict PH; this was used to calculate a positive and negative likelihood ratio following a positive diagnosis of 2.154 and 0.538, respectively., Conclusions: EBUS interrogation of pulmonary artery hemodynamic is safe and feasible. EBUS may be used as a screening test for PH in high-risk individuals., Competing Interests: R.F.C. has received research grants from Siemens and Olympus, and he is paid consultant for Intuitive Surgical, Siemens, and Olympus. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2023 The Author(s).)

Background: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited., Objectives: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF., Methods: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated., Results: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p <0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31-1.74] vs. OR 1.04 [95% CI 0.90-1.20], p interaction <0.001)., Conclusions: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701)., Competing Interests: R.M reports research funding from Bayer, Pfizer, and Tempus; and 18 personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, 19 Caris, Dendreon, Exelixis, Janssen, Johnson and Johnson, Merck & Co, Myovant, Novartis, Pfizer, Sanofi, Sorrento Therapeutics, Tempus, and Vividion. A.N. reports consulting fees from AstraZeneca, Takeda Oncology and Bantam Pharmaceuticals. B.B. reports research support to institution from Amgen, Bicycle Therapeutics, Boehringer Ingelheim, Ikena Oncology, Kahr Medical, Merck, Syros, Tarveda Therapeutics. Z.B. receives research support from 10.13039/100004328Genentech/imCORE and Bristol Myers Squibb. Personal fees from UpToDate. L.A.F reports clinical trial funding from BMS, EMDserono, Pfizer, Merck, Array, Kartos, Incyte, personal fees from Elsevier, ViaOncology, outside the submitted work. J.L.W. reports research funding from NIH/NCI during the conduct of the work, research funding from AACR, consulting fees from Westat, Roche, Flatiron Health, Melax Tech, other from HemOnc.org LLC (ownership), outside the submitted work. C.H reports stock holdings in Johnson and Johnson; research funding to institution from Merck, Bausch Health, Genentech, Bayer, and AstraZeneca, consultant fees from Tempus, Genzyme, and EMD Sorono, speaking fees from OncLive/MJH Life Sciences, travel fees from Merck, all outside the submitted work. The remaining authors have nothing to disclose., (© 2023 Published by Elsevier Inc.)

Neurophysiological investigations over the past decades have demonstrated the involvement of the primate insula in a wide array of sensory, cognitive, affective and regulatory functions, yet the complex functional organization of the insula remains unclear. Here we examined to what extent non-invasive task-based and resting-state fMRI provides support for functional specialization and integration of sensory and motor information in the macaque insula. Task-based fMRI experiments suggested a functional specialization related to processing of ingestive/taste/distaste information in anterior insula, grasping-related sensorimotor responses in middle insula and vestibular information in posterior insula. Visual stimuli depicting social information involving conspecific`s lip-smacking gestures yielded responses in middle and anterior portions of dorsal and ventral insula, overlapping partially with the sensorimotor and ingestive/taste/distaste fields. Functional specialization/integration of the insula was further corroborated by seed-based whole brain resting-state analyses, showing distinct functional connectivity gradients across the anterio-posterior extent of both dorsal and ventral insula. Posterior insula showed functional correlations in particular with vestibular/optic flow network regions, mid-dorsal insula with vestibular/optic flow as well as parieto-frontal regions of the sensorimotor grasping network, mid-ventral insula with social/affiliative network regions in temporal, cingulate and prefrontal cortices and anterior insula with taste and mouth motor networks including premotor and frontal opercular regions., Competing Interests: Declaration of Competing Interest none., (Copyright © 2023. Published by Elsevier Inc.)

Background: Continuous ibrutinib administration is needed to maintain efficacy in patients with chronic lymphocytic leukemia (CLL) and, as such, long-term toxicity is a concern. The authors report the 5-year follow-up of patients with CLL who received treatment with ibrutinib with a focus on hypertension and cardiovascular toxicities., Methods: Patient characteristics were assessed, including blood pressure, cardiovascular disease, disease progression, and death. Univariate logistic regression analysis assessed the relation of patient characteristics and the development of new or worsened hypertension. The incidence of hypertensive outcomes was evaluated using competing risk. Survival was estimated using the Kaplan-Meier method., Results: Three hundred patients with CLL who were treated with ibrutinib on clinical trials were included. The median patient age at study enrollment was 65 years (range, 29-83 years). Seventy percent of patients were men, and 88% were Caucasian. Sixty-nine percent of patients had hypertension at baseline, and 47% were on antihypertensive medication. Eighty-eight percent had relapsed or refractory CLL. New-onset and worsening hypertension were common, occurring in 68.5% and 38% of patients, respectively. Systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg was observed in 16.9% of patients. Hypertension was reversible after ibrutinib discontinuation. Older age, male sex, tobacco use, and chronic kidney disease were associated with ibrutinib-related hypertension. Baseline hypertension was not associated with major adverse cardiovascular events in ibrutinib-treated patients nor with event-free or overall survival., Conclusions: Hypertension is a common toxicity in patients with CLL who receive ibrutinib but is manageable in most patients. Other than chronic kidney disease, baseline cardiovascular disease did not affect ibrutinib-related hypertension nor was hypertension associated with major adverse cardiovascular events or survival., Plain Language Summary: Ibrutinib is an effective treatment for patients with chronic lymphocytic leukemia. Ibrutinib is a well tolerated therapy, however hypertension can develop or worsen in patients receiving ibrutinib and other cardiovascular events are significant challenges to the use of this drug. This may be particularly true in patients with heart disease. Short-term side effects may worsen heart disease, but the long-term impact is unknown. The long-term results of ibrutinib on heart disease and hypertension are described., (© 2023 American Cancer Society.)

Non-human primate (NHP) neuroimaging can provide essential insights into the neural basis of human cognitive functions. While functional magnetic resonance imaging (fMRI) localizers can play an essential role in reaching this objective (Russ et al., 2021), they often differ substantially across species in terms of paradigms, measured signals, and data analysis, biasing the comparisons. Here we introduce a functional frequency-tagging face localizer for NHP imaging, successfully developed in humans and outperforming standard face localizers (Gao et al., 2018). FMRI recordings were performed in two awake macaques. Within a rapid 6 Hz stream of natural non-face objects images, human or monkey face stimuli were presented in bursts every 9 s. We also included control conditions with phase-scrambled versions of all images. As in humans, face-selective activity was objectively identified and quantified at the peak of the face-stimulation frequency (0.111 Hz) and its second harmonic (0.222 Hz) in the Fourier domain. Focal activations with a high signal-to-noise ratio were observed in regions previously described as face-selective, mainly in the STS (clusters PL, ML, MF; also, AL, AF), both for human and monkey faces. Robust face-selective activations were also found in the prefrontal cortex of one monkey (PVL and PO clusters). Face-selective neural activity was highly reliable and excluded all contributions from low-level visual cues contained in the amplitude spectrum of the stimuli. These observations indicate that fMRI frequency-tagging provides a highly valuable approach to objectively compare human and monkey visual recognition systems within the same framework., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: This study examined the role of echocardiographic and cardiac histomorphology parameters in predicting mortality in patients with cardiac AL amyloidosis., Methods: Patients with endomyocardial biopsy-proven cardiac AL amyloidosis treated at MD Anderson Cancer Center between 6/2011 and 6/2020 were identified. Stored echocardiographic images and endomyocardial biopsy samples were processed for myocardial strain analysis and a detailed histomorphology characterization., Results: Of 43 patients; 44% were women and 63% white. Median age was 65 years; 51% underwent stem cell transplantation (SCT). Thirty patients (70%) died during follow up (median follow up: 4.1 years). Lower LA strain (<13.5%) and absence of SCT as a time-varying covariate were significantly associated with increased risk of death in the multivariate cox regression analysis. Higher LV mass and lower RV tricuspid annular plane systolic excursion were associated with increased odds of having ≥5% interstitial amyloid deposition on biopsy in the multivariate logistic regression analysis., Conclusion: Lower LA strain independently predicted mortality in our cohort, and its performance in the routine assessment of AL amyloidosis may be beneficial. Furthermore, SCT for cardiac AL amyloidosis was associated with improved OS. These findings need to be confirmed by larger studies in the era of contemporary systemic therapies., 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., (Copyright © 2023 Koutroumpakis, Niku, Black, Ali, Sadaf, Song, Palaskas, Iliescu, Durand, Yusuf, Lee, Buja, Deswal and Banchs.)

Our objective is to analyze scanpaths acquired through participants achieving a reading task aiming at answering a binary question: Is the text related or not to some given target topic? We propose a data-driven method based on hidden semi-Markov chains to segment scanpaths into phases deduced from the model states, which are shown to represent different cognitive strategies: normal reading, fast reading, information search, and slow confirmation. These phases were confirmed using different external covariates, among which semantic information extracted from texts. Analyses highlighted some strong preference of specific participants for specific strategies and more globally, large individual variability in eye-movement characteristics, as accounted for by random effects. As a perspective, the possibility of improving reading models by accounting for possible heterogeneity sources during reading is discussed., Competing Interests: The author(s) declare(s) that the contents of the article are in agreement with the ethics described in http://biblio.unibe.ch/portale/elibrary/BOP/jemr/ethics.html and that there is no conflict of interest regarding the publication of this paper., (Copyright (©) 2022 Brice Olivier, Anne Guérin-Dugué, Jean-Baptiste Durand.)

Background and Objectives: Cancer and coronary artery disease (CAD) often coexist. Compared to quantitative coronary angiography (QCA), fractional flow reserve (FFR) has emerged as a more reliable method of identifying significant coronary stenoses. We aimed to assess the specific management, safety and outcomes of FFR-guided percutaneous coronary intervention (PCI) in cancer patients with stable CAD. Materials and Methods: FFR was used to assess cancer patients that underwent coronary angiography for stable CAD between September 2008 and May 2016, and were found to have ≥50% stenosis by QCA. Patients with lesions with an FFR > 0.75 received medical therapy alone, while those with FFR ≤ 0.75 were revascularized. Procedure-related complications, all-cause mortality, nonfatal myocardial infarction, or urgent revascularizations were analyzed. Results: Fifty-seven patients with stable CAD underwent FFR on 57 lesions. Out of 31 patients with ≥70% stenosis as measured by QCA, 14 (45.1%) had an FFR ≥ 0.75 and lesions were reclassified as moderate and did not receive PCI nor DAPT. Out of 26 patients with <70% stenosis as measured by QCA, 6 (23%) had an FFR < 0.75 and were reclassified as severe and were treated with PCI and associated DAPT. No periprocedural complications, urgent revascularization, acute coronary syndromes, or cardiovascular deaths were noted. There was a 22.8% mortality at 1 year, all cancer related. Patients who received a stent by FFR assessment showed a significant association with decreased risk of all-cause death (HR: 0.37, 95% CI 0.15−0.90, p = 0.03). Conclusions: Further studies are needed to define the optimal therapeutic approach for cancer patients with CAD. Using an FFR cut-off point of 0.75 to guide PCI translates into fewer interventions and can facilitate cancer care. There was an overall reduction in mortality in patients that received a stent, suggesting increased resilience to cancer therapy and progression.

Symmetry is a highly salient feature of the natural world that is perceived by many species. In humans, the cerebral areas processing symmetry are now well identified from neuroimaging measurements. Macaque could constitute a good animal model to explore the underlying neural mechanisms, but a previous comparative study concluded that functional magnetic resonance imaging responses to mirror symmetry in this species were weaker than those observed in humans. Here, we re-examined symmetry processing in macaques from a broader perspective, using both rotation and reflection symmetry embedded in regular textures. Highly consistent responses to symmetry were found in a large network of areas (notably in areas V3 and V4), in line with what was reported in humans under identical experimental conditions. Our results suggest that the cortical networks that process symmetry in humans and macaques are potentially more similar than previously reported and point toward macaque as a relevant model for understanding symmetry processing., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

As we plan to reach or manipulate objects, we generally orient our body so as to face them. Other objects occupying the same portion of space will likely represent potential obstacles for the intended action. Thus, either as targets or as obstacles, the objects located straight in front of us are often endowed with a special behavioral status. Here, we review a set of recent electrophysiological, imaging and behavioral studies bringing converging evidence that the objects which lie straight-ahead are subject to privileged visual processing. More precisely, these works collectively demonstrate that when gaze steers central vision away from the straight-ahead direction, the latter is still prioritized in peripheral vision. Straight-ahead objects evoke (1) stronger neuronal responses in macaque peripheral V1 neurons, (2) stronger EEG and fMRI activations across the human visual cortex and (3) faster reactive hand and eye movements. Here, we discuss the functional implications and underlying mechanisms behind this phenomenon. Notably, we propose that it can be considered as a new type of visuospatial attentional mechanism, distinct from the previously documented classes of endogenous and exogenous attention., (© 2021. The Author(s).)

Objectives: To assess the clinical impact of Cardiovascular Magnetic Resonance (CMR) in clinical decision making of cancer patients with a suspected cardiomyopathy in a tertiary cancer center. Background: Cardiomyopathies of diverse etiologies are frequently encountered in a Cardio-Oncology practice. The clinical impact of CMR after a presumptive diagnosis of cardiomyopathy has not been studied in cancer patients. Methods: We reviewed data on cancer patients with presumptive diagnosis of cardiomyopathy who underwent CMR in a tertiary cancer center. The clinical impact of CMR was defined as either change in clinical diagnosis or management post CMR results. Univariate and multivariate logistic regression models were used to assess whether any of the baseline characteristics were predictive of the clinical impact of CMR. Results: A total of 110 consecutive patients were identified. Clinical impact of CMR was seen in 68 (62%) patients. Change in the clinical diagnosis and management was seen in 56 (51%) and 41 (37%) of patients, respectively. The most common change was prevention of endomyocardial biopsy in 26 patients (24%). Overall, patients with higher left ventricular ejection fraction (LVEF) by echocardiography (echo), clinical impact was influenced more by CMR (LVEF of 37.2 ± 12.3% vs. 51.5 ± 11.6%, p < 0.001). Cancer diagnosis of multiple myeloma was associated with change in the management post CMR (adjusted OR of 25.6, 95% CI 4.0-162.4, p = 0.001). Suspicion of infiltrative cardiomyopathy was associated with a higher likelihood of change in diagnosis. Having an LVEF≥40 by echo was associated with change in diagnosis and management by CMR. Conclusions: Utilization of CMR has a significant clinical impact in cancer patients with suspected cardiomyopathy. Patients with cancer diagnosis of multiple myeloma, suspicion of infiltrative cardiomyopathy and those with higher LVEF by echo seem to benefit more from CMR., 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., (Copyright © 2021 Heidari-Bateni, Durand, Iliescu, Gladish, Deswal, Patel, Kim, Song, Hassan, Palaskas, Baldassarre, Bucciarelli-Ducci and Lopez-Mattei.)

Aims: Although immune checkpoint inhibitor (ICI) myocarditis carries a high reported mortality, increasing reports of smoldering myocarditis suggest a clinical spectrum of disease. Endomyocardial biopsy (EMB) remains the gold standard for diagnosis of ICI myocarditis, but different pathologic diagnostic criteria exist. The objective of this study was to classify the spectrum of ICI myocarditis and myocardial inflammation by pathology findings on EMB and correlate this with clinical outcomes., Methods and Results: All patients who had EMB at MD Anderson Cancer Center between January 2018 and August 2019 for suspected ICI myocarditis were retrospectively reviewed. A grading system (Grades 0-2) based on the degree of inflammatory infiltrate was developed by pathologists. Cardiovascular outcomes and treatment were compared between grades of pathology. We identified 28 patients who had EMB for suspected ICI myocarditis, of which 18 were positive for myocarditis/inflammation. There were four deaths (two in Grade 2 and two in Grade 1), but only one was attributable to myocarditis. Grade 2 patients had no myocarditis-associated deaths despite having the highest troponin T values (median 2063 pg/mL). Four patients with Grade 1 myocardial inflammation continued ICI without any immunomodulation, and all were alive without adverse cardiovascular events at follow-up., Conclusion: We defined an EMB grading system for ICI myocarditis encompassing a spectrum of histologic findings of inflammatory infiltrates. A subset of low-grade myocardial inflammation patients were able to continue ICI without immunosuppressive therapy. Further studies are needed to identify low-risk patients who can be safely treated with ICI., (© 2021 European Society of Cardiology.)

Introduction: Patients with systemic AL amyloidosis (AL) should be evaluated for cardiac amyloidosis (CA), as prognosis is strongly related to cardiac involvement. We assessed the characteristics of patients referred to cardiac magnetic resonance (CMR) with suspected CA from a cancer center and determine predictors of mortality/heart failure hospitalizations (HFH). Methods: Forty-four consecutive patients referred for CMR with suspected CA were retrospectively included. Variables collected included cardiac biomarkers, in addition to echocardiographic and CMR variables. Survival analyses were performed to determine which variables were more predictive of mortality and HFH. Results: Of the 44 patients included, 55% were females. 73% of patients were diagnosed with CA by CMR; 56% of them had an established diagnosis of AL. Patients with CA by CMR had higher native T1, higher extracellular volume (ECV) fraction, higher T2, less negative GLS by Echo, and higher troponin I and B-type natriuretic peptide (BNP). Kaplan-Meier survival analysis revealed that the following were predictive of mortality: an ECV ≥ 0.50 ( p = 0.0098), CMR LVEF < 50% ( p = 0.0010), T2/ECV ≤ 100 ( p = 0.0001), and troponin I > 0.03 ( p = 0.0025). In a stepwise conditional Cox logistic regression model, the only variable predictive of a composite of mortality and HFH was ECV (HR: 1.17, 95% CI = 1.02-1.34 p = 0.030). Conclusion: ECV seems to be an important biomarker that could be a predictor of outcomes in cardiac AL amyloidosis. In combination, CMR and serum cardiac biomarkers might help to establish prognosis in patients with CA., 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., (Copyright © 2021 Agha, Palaskas, Patel, DeCara, Parwani, Iliescu, Durand, Kim, Hassan, Gladish, Lee, Kaufman and Lopez-Mattei.)

Background: QT prolongation and torsades de pointes pose a major concern for cardiologists and oncologists. Although cancer patients are suspected to have prolonged QT intervals, this has not been investigated in a large population. The purpose of this study was to analyze the QT interval distribution in a cancer population and compare it to a non-cancer population in the same institution. Methods: The study was a retrospective review of 82,410 ECGs performed in cancer patients (51.8% women and 48.2% men) and 775 ECGs performed in normal stem cell donors (47.9% women and 52.1% men) from January 2009 to December 2013 at the University of Texas MD Anderson Cancer Center. Pharmacy prescription data was also collected and analyzed during the same time period. Correction of the QT interval for the heart rate was performed using the Bazett and Fridericia formulas. Results: After QT correction for heart rate by the Fridericia formula (QTcF), the mean and 99% percentile QTc for cancer patients were 414 and 473 ms, respectively. These were significantly longer than the normal stem cell donors, 407 and 458 ms, p < 0.001, respectively. Among the cancer patients, the QTc was longer in the inpatient setting when compared to both outpatient and emergency center areas. The most commonly prescribed QT prolonging medications identified were ondansetron and methadone. Conclusion: Our study demonstrates significantly longer QTc intervals in cancer patients, especially in the inpatient setting. Frequently prescribed QT prolonging medications such as antiemetics and analgesics may have a causative role in QT prolongation seen in our cancer hospital., 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., (Copyright © 2021 Kim, Masha, Olson, Iliescu, Karimzad, Hassan, Palaskas, Durand, Leung and Lopez-Mattei.)

Pediatric, adolescent and young adult (AYA) patients receiving novel cancer immunotherapies may develop associated toxicities with overlapping signs and symptoms that are not always easily distinguished from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/clinical sequelae. We describe 2 diagnostically challenging cases of SARS-CoV-2 and Multi-Inflammatory Syndrome-Adult (MIS-A), in patients with a history of acute lymphoblastic leukemia following cellular therapy administration and review evolving characterization of both the natural course of SARS-CoV-2 infection and toxicities experienced in younger cancer immunotherapy patients. Vigilant monitoring for unique presentations and epidemiologic surveillance to promptly detect changes in incidence of either condition may be warranted., 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., (Copyright © 2021 Ragoonanan, Khazal, Mejia, Ewing, Durand, Bashoura, Tayar, Dailey Garnes, Petropoulos, Tewari, Bhatti, Ahmad, Cortes, Razvi, McBeth, Swinford, Shoberu, Waseemuddin, Chi, Gill, Zaky, Daw, Gutierrez, Tereffe, Kebriaei, Rezvani, Shpall, Champlin and Mahadeo.)

Time-to-contact (TTC) perception refers to the ability of an observer to estimate the remaining time before an object reaches a point in the environment, and is of crucial importance in daily life. Noninvasive correlational approaches have identified several brain areas sensitive to TTC information. Here we report the results of two studies, including one during an awake brain surgery, that aimed to identify the specific areas causally engaged in the TTC estimation process. In Study 1, we tested 40 patients with brain tumor in a TTC estimation task. The results showed that four of the six patients with impaired performance had tumors in right upper parietal cortex, although this tumoral location represented only six over 40 patients. In Study 2, 15 patients underwent awake brain surgery electrostimulation mapping to examine the implication of various brain areas in the TTC estimation process. We acquired and normalized to MNI space the coordinates of the functional areas that influenced task performance. Our results seem to demonstrate that the early stage of the TTC estimation process involved specific cortical territories in the ventral region of the right intraparietal sulcus. Downstream processing of TTC could also involve the frontal eye field (middle frontal gyrus) related to ocular search. We also found that deactivating language areas in the left hemisphere interfered with the TTC estimation process. These findings demonstrate a fine grained, cortical representation of TTC processing close to the ventral right intraparietal sulcus and complement those described in other human studies., (© 2020 Wiley Periodicals LLC.)

Background: Survivors of childhood cancer exposed to cardiotoxic therapies are at significant cardiovascular risk. The utility of cardiac biomarkers for identifying the risk of future cardiomyopathy and mortality is unknown., Methods: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) were assessed in 1213 adults 10 or more years from a childhood cancer diagnosis; 786 were exposed to anthracycline chemotherapy and/or chest-directed radiation therapy (RT). NT-proBNP values above age- and sex-specific 97.5th percentiles were considered abnormal. Generalized linear models estimated cross-sectional associations between abnormal NT-proBNP and anthracycline or chest RT doses as risk ratios with 95% confidence intervals (CIs). A Poisson distribution estimated rates and a Cox proportional hazards model estimated hazard ratios (HRs) for future cardiac events and death., Results: At a median age of 35.5 years (interquartile range, 29.8-42.5 years), NT-proBNP and cTnT were abnormal in 22.5% and 0.4%, respectively. Exposure to chest RT and exposure to anthracycline chemotherapy were each associated with a dose-dependent increased risk for abnormal NT-proBNP (P for trend <.0001). Among exposed survivors with no history of Common Terminology Criteria for Adverse Events-graded cardiomyopathy and with normal systolic function, survivors with abnormal NT-proBNP had higher rates per 1000 person-years of cardiac mortality (2.93 vs 0.96; P < .0001) and future cardiomyopathy (32.10 vs 15.98; P < .0001) and an increased risk of future cardiomyopathy (HR, 2.28; 95% CI, 1.28-4.08) according to a multivariable assessment., Conclusions: Abnormal NT-proBNP values were prevalent and, among survivors who were exposed to cardiotoxic therapy but did not have a history of cardiomyopathy or current systolic dysfunction, identified those at increased risk for future cardiomyopathy. Further longitudinal studies are needed to confirm this novel finding., (© 2020 American Cancer Society.)

We describe a case of testicular teratoma with metastasis to the right ventricle. The mass nearly completely resolved with chemotherapy, obviating the need for upfront surgery. We review the workup of intracardiac metastatic tumors. ( Level of Difficulty: Intermediate. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

In humans, the posterior cingulate cortex contains an area sensitive to visual cues to self-motion. This cingulate sulcus visual area (CSv) is structurally and functionally connected with several (multi)sensory and (pre)motor areas recruited during locomotion. In nonhuman primates, electrophysiology has shown that the cingulate cortex is also related to spatial navigation. Recently, functional MRI in macaque monkeys identified a cingulate area with similar visual properties to human CSv. In order to bridge the gap between human and nonhuman primate research, we examined the structural and functional connectivity of putative CSv in three macaque monkeys adopting the same approach as in humans based on diffusion MRI and resting-state functional MRI. The results showed that putative monkey CSv connects with several visuo-vestibular areas (e.g., VIP/FEFsem/VPS/MSTd) as well as somatosensory cortex (e.g., dorsal aspects of areas 3/1/2), all known to process sensory signals that can be triggered by self-motion. Additionally, strong connections are observed with (pre)motor areas located in the dorsal prefrontal cortex (e.g., F3/F2/F1) and within the anterior cingulate cortex (e.g., area 24). This connectivity pattern is strikingly reminiscent of that described for human CSv, suggesting that the sensorimotor control of locomotion relies on similar organizational principles in human and nonhuman primates., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Survivors of childhood cancer have an increased risk of therapy-related cardiovascular disease. It is not known whether family history of cardiovascular disease further increases risk of adverse cardiovascular outcomes among survivors., Methods: Family history of cardiovascular disease was collected from 1,260 survivors [median age at diagnosis, 8 years (range, 0-23); age at last follow-up, 35 years (range, 18-66)] of childhood cancer in the St. Jude Lifetime Cohort Study. Multivariable risk models evaluated associations with cardiovascular disease (Common Terminology Criteria for Adverse Events grade 2-4 events) and cardiovascular risk factors., Results: Among survivors exposed to chest-directed radiation and/or anthracycline chemotherapy ( n = 824), 7% reported a first-degree family history of heart failure, 19% myocardial infarction, 11% stroke, 26% atherosclerotic disease (myocardial infarction and/or stroke), 62% hypertension, and 31% diabetes mellitus. Eighteen percent of exposed survivors developed heart failure, 9% myocardial infarction, 3% stroke, 11% atherosclerotic disease, 30% hypertension, and 9% diabetes mellitus. Having a first-degree family history of atherosclerotic disease was independently associated with development of treatment-related heart failure [RR, 1.38; 95% confidence interval (CI), 1.01-1.88; P = 0.04] among exposed survivors. Risk for hypertension was increased among exposed survivors with a first-degree family history of hypertension (RR, 1.55; 95% CI, 1.26-1.92; P < 0.0001) or of any cardiovascular disease [myocardial infarction, stroke, or heart failure (RR, 1.30; 95% CI, 1.06-1.59; P = 0.01)]., Conclusions: Family history of cardiovascular disease and cardiovascular risk factors independently increased risk of heart failure and hypertension among survivors of childhood cancer exposed to cardiotoxic therapies., Impact: These data show the importance of cardiovascular family history as a risk factor for cardiovascular disease in survivors of childhood cancer., (©2020 American Association for Cancer Research.)

The growing success of immune checkpoint inhibitors (ICIs) has led to improved outcomes in several types of cancers with studies looking for expanding their indications and use. However immune-related adverse events have been recognized of which myocarditis is associated with a high mortality. Other cardiac events such as arrhythmias, pericardial disease, and coronary atherosclerosis have been observed in patients on ICI therapy. These cardiac toxicities are thought to be the result of increased inflammatory responses after inhibition of specific checkpoint proteins on T cells. Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant myocarditis, hemodynamic instability, and cardiac arrest. We will review the most commonly reported cardiovascular toxicities associated with ICIs and their management., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Key Points: We performed a prospective electrostimulation study of the motor homunculus in 100 patients without motor deficit or brain lesion in the precentral gyrus in order to acquire accurate Montreal Neurological Institute (MNI) coordinates of the functional areas. The analysis of 248 body coordinates in the precentral gyrus showed rare inter-individual variations in the medial-to-lateral somatotopic movement organization with quite similar intensity thresholds. Electrostimulation only induced basic and stereotyped movements. We detected a relative medial-to-lateral somatotopy of the wrist/hand/global/individual fingers, with sometimes different sites for an individual muscle or movement. We found some similarities to, but also substantial differences from, the seminal work of Penfield and colleagues. We propose an updated version of the human motor homunculus and of its correlation with the somatosensory homunculus, previously defined in MNI space with a similar brain mapping technique., Abstract: In this prospective electrostimulation study, based on 100 operated patients without motor deficit or brain lesion in the precentral gyrus, we acquired coordinates of the functional areas of the motor homunculus and normalized them to standard MNI space. Among 608 sites stimulated in the precentral gyrus (and 1937 in gyri nearby), 248 positive points (40%) for motor response were detected - 245 in the precentral gyrus. Positive stimulations were detected through the 'on/off' outbreak effect, and only basic movements were detected. We found no significant difference in mean intensity threshold between the motor representations of the fingers (1.94 mA), tongue and lower limbs (both 2.0 mA), or face (2.25 mA). In the precentral gyrus, the evoked body movements displayed a medial-to-lateral somatotopy in very small (often <10 mm 2 ) areas. The hand region displayed multiple areas for a specific movement, with areas inducing either global or single-finger movement (with a relative medial-to-lateral somatotopy). Among these tested patients, the somatotopic organization of the intact motor cortex showed little inter-individual variations. Unlike Penfield and collaborators, we evoked no sensations such as sense of movement or desire to move, and only 2% of motor responses outside the precentral gyrus. We propose a rationalization of the standard drawing of the motor homunculus according to MNI space. We found a somatotopic correlation perpendicular to the central sulcus when matching our motor data to those previously obtained for the somatosensory homunculus., (© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.)

Background: Anthracycline-induced cardiomyopathy (AIC) may be irreversible with a poor prognosis, disproportionately affecting women and young adults. Administration of allogeneic bone marrow-derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure (HF) treatment., Objectives: SENECA (Stem Cell Injection in Cancer Survivors) was a phase 1 study of allo-MSCs in AIC., Methods: Cancer survivors with chronic AIC (mean age 56.6 years; 68% women; NT-proBNP 1,426 pg/ml; 6 enrolled in an open-label, lead-in phase and 31 subjects randomized 1:1) received 1 × 10 8 allo-MSCs or vehicle transendocardially. Primary objectives were safety and feasibility. Secondary efficacy measures included cardiac function and structure measured by cardiac magnetic resonance imaging (CMR), functional capacity, quality of life (Minnesota Living with Heart Failure Questionnaire), and biomarkers., Results: A total of 97% of subjects underwent successful study product injections; all allo-MSC-assigned subjects received the target dose of cells. Follow-up visits were well-attended (92%) with successful collection of endpoints in 94% at the 1-year visit. Although 58% of subjects had non-CMR compatible devices, CMR endpoints were successfully collected in 84% of subjects imaged at 1 year. No new tumors were reported. There were no significant differences between allo-MSC and vehicle groups with regard to clinical outcomes. Secondary measures included 6-min walk test (p = 0.056) and Minnesota Living with Heart Failure Questionnaire score (p = 0.048), which tended to favor the allo-MSC group., Conclusions: In this first-in-human study of cell therapy in patients with AIC, transendocardial administration of allo-MSCs appears safe and feasible, and CMR was successfully performed in the majority of the HF patients with devices. This study lays the groundwork for phase 2 trials aimed at assessing efficacy of cell therapy in patients with AIC.

We investigated the visuotopic organization of macaque posterior parietal cortex (PPC) by combining functional imaging (fMRI) and wide-field retinotopic mapping in two macaque monkeys. Whole brain blood-oxygen-level-dependent (BOLD) signal was recorded while monkeys maintained central fixation during the presentation of large rotating wedges and expending/contracting annulus of a "shaking" fruit basket, designed to maximize the recruitment of PPC neurons. Results of the surface-based population receptive field (pRF) analysis reveal a new cluster of four visuotopic areas at the confluence of the parieto-occipital and intra-parietal sulci, in a location previously defined histologically and anatomically as the posterior intra-parietal (PIP) region. This PIP cluster groups together two recently described areas (CIP1/2) laterally and two newly identified ones (PIP1/2) medially, whose foveal representations merge in the fundus of the intra-parietal sulcus. The cluster shares borders with other visuotopic areas: V3d posteriorly, V3A/DP laterally, V6/V6A medially and LIP anteriorly. Together, these results show that monkey PPC is endowed with a dense set of visuotopic areas, as its human counterpart. The fact that fMRI and wide-field stimulation allows a functional parsing of monkey PPC offers a new framework for studying functional homologies with human PPC.

Background: Oncological patients have several additional risk factors for developing a cardiac implantable electronic device (CIED)-related infection. Therefore, we evaluated the clinical impact of our comprehensive bundle approach that includes the novel minocycline and rifampin antimicrobial mesh (TYRX) for the prevention of CIED infections in patients living with cancer., Methods: We retrospectively reviewed all consecutive patients who had a CIED placement at our institution during 2012-2017 who received preoperative vancomycin, intraoperative pocket irrigation with bacitracin and polymyxin B, plus TYRX antimicrobial mesh, followed by postoperative oral minocycline., Results: A total of 154 patients had a CIED, with 97 permanent pacemakers (PPMs), 23 implantable cardioverter defibrillators (ICDs), and 34 cardiac resynchronization therapy (CRT) devices. An underlying solid cancer was present in 62% of patients, while 38% had a hematologic malignancy. Apart from a higher proportion of surgical interventions in the PPM group than in the ICD and CRT groups ( P = .007), no other oncologic variables were statistically significantly different between groups. Despite an extensive median follow-up period (interquartile range) of 21.9 (6.7-33.8) months, 16 patients (10%) had a mechanical complication, while only 2 patients (1.3%) developed a CIED infection, requiring the device to be explanted., Conclusions: Our comprehensive prophylactic bundle approach using TYRX antimicrobial mesh in an oncologic population at high risk for infections was revealed upon extensive follow-up to be both safe and effective in maintaining the rate of CIED infection at 1.3%, well within published averages in the broader population of CIED recipients., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The benefits of invasive versus noninvasive management in oncology patients with acute myocardial infarction (AMI) are unclear. We aimed to retrospectively determine outcome differences between conservative and invasive management of AMI in cancer patients., Methods: Patients from our institution between March 2016 and December 2018 with type 1 and type 2 AMI (excluding STEMI) were classified into 2 groups: medical therapy only and invasive strategies. Analyzed outcomes were overall survival (OS), procedural complications, subsequent events, and hospice referral. Kaplan-Meier method and log-rank test were used to compare OS between subgroups. Cox proportional hazards regression analyses were conducted to find factors associated with OS., Results: We included 201 patients. Type 1 MI was seen in 152 patients (76%) and type 2 MI in 49 (24%). Median OS was 13 months. Most presented with symptoms other than dyspnea or chest pain (49%) and with ECG revealing changes other than ST-segment depression and T-wave inversion (62%). Patients with type 2 MI had worse OS than patients with type 1 MI (HR = 2.3, p = 0.0002). Early coronary angiography (≤72 h; HR = 0.327, p < 0.0001), late coronary angiography (>72 h; HR = 0.496, p = 0.0426), and percutaneous coronary intervention (HR = 0.481, p = 0.0116) were associated with better OS than noninvasive approaches. Single and dual agent antiplatelet therapy, beta blockers, and statins were each associated with better OS., Conclusions: Cancer patients without STEMI who underwent invasive treatment for AMI had better OS compared with those treated only medically, with the highest benefit when coronary angiography was performed within 72 h of admission for AMI., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Importance: Exercise intolerance is associated with increased risk for morbidity and mortality in childhood cancer survivors. However, an association between exercise intolerance and psychosocial outcomes has not been fully explored., Objective: To examine the associations between exercise intolerance and emotional distress, attainment of social roles, and health-related quality of life in childhood cancer survivors., Design, Setting, and Participants: A cross-sectional study including 1041 adult survivors of childhood cancer and 286 community controls in the St Jude Lifetime Cohort was conducted at St Jude Children's Research Hospital. The study was performed from April 1, 2012, to March 15, 2020., Exposures: Exercise intolerance was defined as relative peak oxygen uptake less than 85% of age- and sex-estimated levels from maximal cardiopulmonary exercise testing., Main Outcomes and Measures: Emotional distress was measured with the 18-item Brief Symptom Inventory-18, which includes overall Global Severity Index and depression, anxiety, and somatization subscales. Participants with T scores greater than or equal to 63 were classified as having elevated levels of distress. Social attainment was evaluated using patient-reported educational, employment, and marital status. Health-related quality of life was examined with the Medical Outcomes Survey Short Form-36. Participants with T scores less than or equal to 40 were classified as reporting poor health-related quality of life., Results: Of the 1041 participants, 528 were women (50.7%). The prevalence of exercise intolerance among survivors (mean [SD] age, 35.5 [9.2] years) was higher than that among controls (age, 34.5 [10.0] years) (survivors: 634 [60.9%] vs controls: 75 [26.2%], P < .001). After adjusting for age at diagnosis and cardiopulmonary exercise testing, sex, race/ethnicity, smoking, physical activity, and exercise intolerance were associated with an increased risk for anxiety (prevalence rate ratio [PRR], 1.95; 95% CI, 1.20-3.16), somatization (PRR, 1.86; 95% CI, 1.23-2.80), and unemployment (PRR, 1.76; 95% CI, 1.23-2.52); an inverse association was noted with having a college degree (PRR, 0.67; 95% CI, 0.50-0.88). Exercise intolerance was associated with an increased the risk for scoring less than or equal to 40 on the physical component summary of the Medical Outcomes Survey Short Form-36 (PRR, 3.69; 95% CI, 2.34-5.84). These associations persisted when either cancer treatment exposures or chronic health conditions were added to the model., Conclusions and Relevance: The findings of this study suggest that exercise intolerance is independently associated with emotional distress, attainment of social roles, and health-related quality of life of long-term survivors of childhood cancer. The results also suggest that improving physiologic capacity may benefit general health and wellness, as well as emotional health, ability to participate in social roles, and health-related quality of life.

The cortical areas that process disparity-defined motion-in-depth (i.e., cyclopean stereomotion [CSM]) were characterized with functional magnetic resonance imaging (fMRI) in two awake, behaving macaques. The experimental protocol was similar to previous human neuroimaging studies. We contrasted the responses to dynamic random-dot patterns that continuously changed their binocular disparity over time with those to a control condition that shared the same properties, except that the temporal frames were shuffled. A whole-brain voxel-wise analysis revealed that in all four cortical hemispheres, three areas showed consistent sensitivity to CSM. Two of them were localized respectively in the lower bank of the superior temporal sulcus (CSMSTS) and on the neighboring infero-temporal gyrus (CSMITG). The third area was situated in the posterior parietal cortex (CSMPPC). Additional regions of interest-based analyses within retinotopic areas defined in both animals indicated weaker but significant responses to CSM within the MT cluster (most notably in areas MSTv and FST). Altogether, our results are in agreement with previous findings in both human and macaque and suggest that the cortical areas that process CSM are relatively well preserved between the two primate species., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objectives: To evaluate the role of platelet count and thromboelastogram (TEG) in the treatment of thrombocytopenic cancer patients with suspected coronary artery disease (CAD). Background: Cancer patients with CAD and thrombocytopenia are often treated non-invasively (i.e., without coronary angiography when clinically indicated) due to perceived high risk of bleeding. We sought to evaluate coagulability based on TEG and determine if platelet count and TEG could predict bleeding risk/mortality among cancer patients undergoing coronary angiography (CA). Methods: Baseline demographics, platelet count, and TEG parameters were recorded among cancer patients that underwent CA and had a concomitant TEG. Logistic regression and univariate proportional hazards regression analysis were performed to determine the impact of platelet count and coagulability on 24-month overall survival (OS). Results: All patients with platelet count <20,000/mm 3 and nearly all patients with platelet count 20,000-49,000/mm 3 were hypocoagulable based on TEG results. In contrast, nearly all patients with platelet counts of 50,000-99,999/mm 3 had normal TEG results and OS similar to those with platelet counts of ≥100,000/mm 3 . Coagulability based on TEG was not associated with OS. However, a platelet count of <50,000/mm 3 was associated with worse 24-month OS (hazard ratio = 2.76; p = 0.0072) when compared with a platelet count of ≥100,000/mm 3 . No major bleeding complications were observed in all groups. Conclusion: The majority of cancer patients with platelet counts of <50,000/mm 3 were hypocoagulable based on TEG and had worse OS at 24 months. The relatively normal TEGs in the >50,000/mm 3 groups, as well as the improved survival, suggest that with appropriate clinical indication and risk/benefit assessment, a cut-off of 50,000/mm 3 platelets can be considered for CA in cancer patients., (Copyright © 2020 Agha, Gill, Balanescu, Donisan, Palaskas, Lopez-Mattei, Hassan, Kim, Charitakis, Cilingiroglu, Oo, Kroll, Durand, Hirsch-Ginsberg, Marmagkiolis and Iliescu.)

The growing success of immune checkpoint inhibitors (ICIs) has led to effectively treating several types of cancers. Even though their use has been associated with the development of cardiac adverse effects, which may decrease the overall survival in cancer patients. These cardiac toxicities are thought to be the result of targeting specific checkpoint proteins on normal myocardial cells leading to over stimulation of the immune system as well as secondary downstream off-target effects on normal tissue.Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant myocarditis, hemodynamic instability, and cardiac arrest.We will review the most commonly reported cardiovascular toxicities associated with ICIs and their management.

The objects located straight-ahead of the body are preferentially processed by the visual system. They are more rapidly detected and evoke stronger BOLD responses in early visual areas than elements that are retinotopically identical but located at eccentric spatial positions. To characterize the dynamics of the underlying neural mechanisms, we recorded in 29 subjects the EEG responses to peripheral targets differing solely by their locations with respect to the body. Straight-ahead stimuli led to stronger responses than eccentric stimuli for several components whose latencies ranged between 70 and 350 ms after stimulus onset. The earliest effects were found at 70 ms for a component that originates from occipital areas, the contralateral P1. To determine whether the straight-ahead direction affects primary visual cortex responses, we performed an additional experiment (n = 29) specifically designed to generate two robust components, the C1 and C2, whose cortical origins are constrained within areas V1, V2 and V3. Our analyses confirmed all the results of the first experiment and also revealed that the C2 amplitude between 130 and 160 ms after stimulus onset was significantly stronger for straight-ahead stimuli. A frequency analysis of the pre-stimulus baseline revealed that gaze-driven alterations in the visual hemi-field containing the straight-ahead direction were associated with a decrease in alpha power in the contralateral hemisphere, suggesting the implication of specific neural modulations before stimulus onset. Altogether, our EEG data demonstrate that preferential responses to the straight-ahead direction can be detected in the visual cortex as early as about 70 ms after stimulus onset.

Purpose: Exercise intolerance, associated with heart failure and death in general populations, is not well studied in survivors of childhood cancer. We examined prevalence of exercise intolerance in survivors exposed or not to cardiotoxic therapy, and associations among organ system function, exercise intolerance, and mortality., Methods: Participants consisted of 1,041 people who had survived cancer ≥ 10 years (and had or did not have exposure to anthracyclines and/or chest-directed radiation) and 285 control subjects. Exercise intolerance was defined as peak oxygen uptake < 85% predicted from maximal cardiopulmonary exercise testing; organ functions were ascertained with imaging or clinical testing. Multivariable regression of the data was performed to compare exercise capacity between survivors exposed or unexposed to cardiotoxic therapy and control subjects, and to evaluate associations between treatment and organ function, and organ function and exercise intolerance. Propensity score methods in time-to-event analyses evaluated associations between exercise intolerance and mortality., Results: Survivors (mean age ± standard deviation [SD], 35.6 ± 8.8 years) had lower mean (± SD) peak oxygen uptake (exposed: 25.74 ± 8.36 mL/kg/min; unexposed: 26.82 ± 8.36 mL/kg/min) than did control subjects (32.69 ± 7.75 mL/kg/min; P for all < .001). Exercise intolerance was present in 63.8% (95% CI, 62.0% to 65.8%) of exposed survivors, 55.7% (95% CI, 53.2% to 58.2%) of unexposed survivors, and 26.3% (95% CI, 24.0% to 28.3%) of control subjects, and was associated with mortality (hazard ratio, 3.9; 95% CI, 1.09 to 14.14). Global longitudinal strain (odds ratio [OR], 1.71; 95% CI, 1.11 to 2.63), chronotropic incompetence (OR, 3.58; 95% CI, 1.75 to 7.31); forced expiratory volume in 1 second < 80% (OR, 2.59; 95% CI, 1.65 to 4.09), and 1 SD decrease in quadriceps strength (OR, 1.49; 95% CI, 1.23 to 1.82) were associated with exercise intolerance. Ejection fraction < 53% was not associated with exercise intolerance., Conclusion: Exercise intolerance is prevalent among childhood cancer survivors and associated with all-cause mortality. Treatment-related cardiac (detected by global longitudinal strain), autonomic, pulmonary, and muscular impairments increased risk. Survivors with impairments may require referral to trained specialists to learn to accommodate specific deficits when engaging in exercise.

Innovations and discoveries in cancer therapeutics have improved survival rates in patients with various types of malignancies. At the same time, physicians are identifying an increased number of patients with treatment-related cardiotoxicity. It is imperative that physicians recognize early treatment-related adverse effects to determine the safest therapeutic options for patients with cancer. This manuscript evaluates the role of cardiovascular imaging and biomarkers in identifying cardiotoxicity trigged by various chemotherapeutic agents and summarizes expert consensus statements regarding cardiotoxicity monitoring., Competing Interests: Conflict of Interest Disclosure: All authors have completed and submitted the Methodist DeBakey Cardiovascular Journal Conflict of Interest Statement and none were reported., (© 2019 Houston Methodist Hospital Houston, Texas.)

Objective: The purpose of this study was to characterize the reproducibility of language trials within and between brain mapping sessions., Methods: Brain mapping and baseline testing data from 200 adult patients who underwent resection of left-hemisphere tumors were evaluated. Data from 11 additional patients who underwent a second resection for recurrence were analyzed separately to investigate reproducibility over time. In all cases, a specific protocol of electrostimulation brain mapping with a controlled naming task was used to detect language areas, and the results were statistically compared with preoperative and intraoperative baseline naming error rates. All patients had normal preoperative error rates, controlled for educational level and age (mean 8.92%, range 0%-16.25%). Intraoperative baseline error rates within the normal range were highly correlated with preoperative ones (r = 0.74, p < 10-10), although intraoperative rates were usually higher (mean 13.30%, range 0%-26.67%). Initially, 3 electrostimulation trials were performed in each cortical area. If 2 of 3 trials showed language interference, 1 or 2 additional trials were performed (depending on results)., Results: In the main group of 200 patients, there were 82 single interferences (i.e., positive results in 1 of 3 trials), 227 double interferences (2/3), and 312 full interferences (3/3). Binomial statistics revealed that full interferences were statistically significant (vs intraoperative baseline) in 92.7% of patients, while double interferences were significant only in 38.5% of patients, those with the lowest error rates. On further testing, one-third of the 2/3 trials became 2/4 trials, which was significant in only one-quarter of patients. Double interference could be considered significant for most patients (> 90%) when confirmed by 2 subsequent positive trials (4/5). In the 11 patients who were operated on twice, only 26% of areas that tested positive in the initial operation tested positive in the second and showed the same type of interference and the same current threshold (i.e., met all 3 criteria)., Conclusions: Electrostimulation trials in awake brain mapping produced graded patterns of positive reproducibility levels, and their significance varied with the baseline error rates. The results suggest that caution is warranted when 2 of 3 trials are positive, although the need for additional trials depends on the individual patients' baseline error rates. Reproducibility issues should be considered in the interpretation of data from awake brain mapping.

Purpose of Review: Current oncologic treatments have shown improvement in overall survival in cancer patients. However, the cardiac toxicities of cancer therapeutics, particularly chemotherapy, targeted therapy and immunotherapy can have life-threatening side effects., Recent Findings: A MEDLINE search for cardiovascular toxicities associated with Federal Drug Administration (FDA)-approved cancer treatments including chemotherapy, targeted therapy and immunotherapy was performed. We included comprehensive articles and research articles establishing the incidence, diagnosis, monitoring and management of cardiovascular toxicities related to cancer treatments until January 2019.This review highlights the mechanisms and epidemiology of cardiotoxicity associated with some cancer treatments. The most common cardiovascular side-effects are discussed at an introductory level with emphasis on those related with the development of heart failure., Summary: Cardiovascular side effects of cancer treatments are common and might affect the survival in cancer patients. Recognition and management of these side effects require understanding of their mechanisms and their clinical manifestations. A multidisciplinary approach with understanding of both the cardiovascular and oncologic risks is necessary in order to provide well tolerated and effective cardio-oncology care.

Purpose: Cancer treatment-related heart failure (HF) is an emerging health concern, as the number of survivors is increasing rapidly, and cardiac health issues are a leading cause of mortality in this population. While there is general evidence for the efficacy of exercise rehabilitation interventions, more research is needed on exercise rehabilitation interventions for patients specifically with treatment-induced HF and whether such interventions are safe and well-accepted. This study provides feasibility and health outcomes of a pilot exercise intervention for cancer survivors with chemotherapy-induced HF., Methods: Twenty-five participants were randomized to a clinic-based exercise intervention or a wait-list control group or, alternatively, allowed to enroll in a home-based exercise intervention if they declined the randomized study. For purposes of analysis, both types of exercise programs were combined into a single intervention group. Repeated-measures analysis of variance was conducted to assess for significant time and treatment group main effects separately and time × treatment group interaction effects., Results: Significant improvements in maximum oxygen uptake ((Equation is included in full-text article.)O2max) were observed in the intervention group. Intervention satisfaction and adherence were high for both clinic- and home-based interventions, with no reported serious adverse events. Enrollment was initially low for the clinic-based intervention, necessitating the addition of the home-based program as an intervention alternative., Conclusions: Results suggest that exercise rehabilitation interventions are feasible in terms of safety, retention, and satisfaction and have the potential to improve (Equation is included in full-text article.)O2max. To maximize adherence and benefits while minimizing participant burden, an ideal intervention may incorporate elements of both clinic-based supervised exercise sessions and a home-based program.

Case reports have reported immune checkpoint inhibitors (ICI), especially nivolumab, are associated with recurrent pericardial effusions. Our objective was to determine how often patients being treated with ICI develop hemodynamically significant pericardial effusion requiring pericardiocentesis compared with other cancer therapeutics and whether the survival of patients who underwent pericardiocentesis differs according to ICI use versus standard cancer therapeutics. Our institutional review board approved catheterization laboratory data collection for all pericardiocenteses performed and all patients receiving ICI from January 1, 2015 to December 31, 2017. Retrospective review of the electronic medical record was performed to identify cancer therapeutics given preceding pericardiocentesis. Log-rank analysis was performed to compare survival in patients requiring pericardiocentesis between those on ICI and those not on ICI. Overall, 3,966 patients received ICI of which only 15 pericardiocenteses were required, including 1 repeat pericardiocentesis in a patient on nivolumab. The prevalence of pericardiocentesis among patients on ICI was 0.38% (15/3,966). Eleven pericardiocenteses were performed after nivolumab infusion, 3 after pembrolizumab, and 1 after atezolizumab, with pericardiocentesis prevalences for each agent of 0.61% (11/1,798), 0.19% (3/1,560), and 0.32% (1/309), respectively. One hundred and twenty pericardiocentesis were performed on patients receiving other cancer therapeutics although no therapeutic agent was associated with more pericardiocenteses than nivolumab. In conclusion, the prevalence of hemodynamically significant pericardial effusions and ICI administration is uncommon, and survival durations after pericardiocentesis for patients receiving ICI and those not receiving ICI are similar, suggesting that frequent echocardiographic monitoring for pericardial effusions is not necessary., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Art experts have argued that the mirror reversal of pictorial artworks produces an alteration of their spatial content. However, this putative asymmetry of the pictorial space remains to be empirically proved and causally explained. Here, we address these issues with the "corridor illusion," a size illusion triggered by the pictorial space of a receding corridor. We show that mirror-reversed corridors-receding respectively leftward and rightward-induce markedly different illusion strengths and thus convey distinct pictorial spaces. Remarkably, the illusion is stronger with the rightward corridor among native left-to-right readers (French participants, n = 40 males) but conversely stronger with the leftward corridor among native right-to-left readers (Syrian participants, n = 40 males). Together, these results demonstrate an asymmetry of the pictorial space and point to our reading/writing habits as a major cause of this phenomenon.