The Society for Cardiovascular Magnetic Resonance (SCMR) last published its comprehensive expert panel report of clinical indications for CMR in 2004. This new Consensus Panel report brings those indications up to date for 2020 and includes the very substantial increase in scanning techniques, clinical applicability and adoption of CMR worldwide. We have used a nearly identical grading system for indications as in 2004 to ensure comparability with the previous report but have added the presence of randomized controlled trials as evidence for level 1 indications. In addition to the text, tables of the consensus indication levels are included for rapid assimilation and illustrative figures of some key techniques are provided. Cardiovascular magnetic resonance (CMR) is established in clinical practice for the diagnosis and management of diseases of the cardiovascular system. However, current guidelines for when this technique should be employed in clinical practice have not been revised since the previous Consensus Panel report of 2004 . ConsideThe Consensus Panel recommendations are based on evidence compiled from the literature and expert experience. Consensus on the evidence classes was achieved by a modified Delphi process. First the section (co-)authors suggested evidence classes for the indications in their respective sections. These were reviewed by all other authors in at least three written rounds of commentary. Evidence classes were finalized with all authors of the documents present in a telephone conference. When insufficient evidence is present in the literature, this is indicated in the report and recommendations are made conservatively under these circumstances. The appropriateness of using CMR is described for the frequent disease entities where imaging information may be warranted. The diagnostic use of CMR will be described in the context of other, competing non-invasive imaging techniques, with particular emphasis on the differential indications with respect to echocardiography.Class I = provides clinically relevant information and is usually appropriate; may be used as first line imaging technique; usually supported by substantial literature or randomised controlled trial(s).Class II = provides clinically relevant information and is frequently useful; other techniques may provide similar information; supported by limited literature.Class III = provides clinically relevant information but is infrequently used because information from other imaging techniques is usually adequate.Class Inv = potentially useful, but still investigational.The usefulness of CMR in specific diseases is summarized by means of the following classification:This classification is not meant to equate to American Heart Association/American (AHA), American College of Cardiology (ACC) and European Society of Cardiology (ESC) consensus documents. We have used nearly the identical classification system that was used for the original Consensus Panel report of 2004, in order to maintain parity with that report so that advances in the field can be readily identified. Because of broad variation in the number of relevant papers between topics, we did not use an arbitrary number of papers for each class. Class 1 indications required the highest level of evidence, for example affirmative randomized controlled trials (RCT) results for use of perfusion CMR. The categories were populated by consensus. The quality of the publications  was germane to the Consensus Panel discussion of ranking of class throughout the discussions. Thus, the only change from 2004 is to add the positive outcome of RCTs in CMR as evidence for level 1 indications. It should also be noted that the classification system for imaging technologies does not easily accord with that of therapeutic trials because the datasets are smaller, multicentre trials are uncommon and randomized controlled trials the exception. The continuing technical and clinical advances in CMR will change the indication’s tables, and therefore between formal reports, the Consensus Panel may post updates online.CMR is a well-established modality for the diagnosis and follow-up of patients with congenital heart disease (CHD) Table . This isWhen performing CMR in CHD patients, it is important to tailor the acquisition parameters to the faster heart rates and smaller structures in children, as well as the limited breath-holding ability of children and poorly compensated adult CHD patients. It is also necessary to have thorough knowledge of CHD anatomy and the extensive array of surgical and catheter interventions. Therefore, it is highly recommended that CMR in CHD patients is performed in centers with sufficient experience and expertise.In younger children with CHD, TTE is often sufficient for initial diagnosis. However, CMR can provide important additional information in lesions with complex intracardiac anatomy or vascular abnormalities. In adults with CHD, TTE is often limited by poor image quality and reduced field of view. Thus, CMR with its reliable visualization of intracardiac and vascular anatomy takes on a central role in the routine non-invasive imaging of these patients. This indication has been recognized in recent guidelines regarding multi-modality imaging and the management of adults with CHD –11. AnotFor shunt lesions, CMR is used to delineate anatomy and determine physiological importance through measurement of the Qp:Qs ratio and ventricular volumes. This is vital information for determining the necessity and timing of surgical or catheter interventions. Studies have shown that CMR can provide definitive diagnosis and evaluation of sinus venosus defects and anomalous pulmonary venous connection , 23 Fig. This isCHD may be associated with abnormalities in the cardiac valves. Echocardiography is often the primary modality for assessing valve morphology and function. CMR is principally used to evaluate the physiological impact of valve regurgitation by measuring the regurgitation volume, regurgitant fraction, and ventricular size and function. This information plays an important role in deciding the timing of mechanical interventions. With valve stenosis, CMR can be used to define orifice size  but may Congenital abnormalities of the aorta, pulmonary arteries, and coronary arteries may occur in isolation or in association with other CHD lesions. The ability to assess these structures by echocardiography becomes progressively more difficult as patients become larger, and CMR angiography techniques serve as an important non-invasive alternative –44. In cConotruncal lesions include tetralogy of Fallot, transposition of the great arteries (TGA), double outlet RV, and truncus arteriosus, among others. The primary imaging modality for these conditions in younger children is echocardiography. CMR may augment the preoperative assessment of double outlet RV by better characterizing the intracardiac anatomy, particularly through use of virtual and 3D printed models , 63. CMRThe reliable visualization of intracardiac and vascular anatomy, large field of view, and 3D imaging capabilities all make CMR well-suited for the diagnosis of complex cardiovascular anatomic arrangements, such as those seen in more severe forms of heterotaxy syndrome , 80. CMR3. On modern hardware this high spatial resolution can be obtained in a single breath hold, which is necessary for chest and abdominal CE-CMRA. For some clinical indications it is advisable to use a multi-phase dynamic acquisition as this can provide information about the direction of blood flow as well as information about tissue perfusion. Since dynamic CE-CMRA demands a higher temporal resolution this typically comes at the expense of spatial resolution. In selected cases it can therefore be useful to perform both acquisitions with two separate injections of contrast agent. Although the vast majority of CE-CMRA studies are performed with GBCA, a substantial body of literature has been published on the use of ferumoxytol as a CMRA contrast agent. Ferumoxytol is an intravenous iron preparation for treatment of the anemia of chronic kidney disease [CMR is a highly reliable modality for depiction of the presence and extent of acquired vascular disease in virtually all of the large and medium sized arteries in the body Table . A varie disease . It is a disease . This phOver the past few years all major hardware vendors have also introduced non-contrast or native CMRA sequences on their platforms. These sequences utilize intrinsic contrast between flowing blood and stationary tissues as the basis to generate angiograms. Different technical approaches are also well described . Major aIn addition to angiography, the wide variety of soft tissue contrast available on CMR  can be applied to vascular imaging to assess features of vessel wall such as haematoma/thrombus, inflammation, and atherosclerotic plaque. In addition to morphologic imaging of blood vessels, velocity mapping can be used to assess and measure the blood flow. Blood velocity and flow can be integrated across the cardiac cycle and the vessel lumen for reliable volume flow measurements. This information is complementary to the anatomical information obtained with the luminographic techniques and can add value in many clinical scenarios .CMR techniques are well-suited to depict the thoracic and abdominal aorta. The high spatial resolution can be used for accurate assessment of aortic size, diameter and the presence and morphology of aortic aneurysms. The near isotropic spatial resolution ensures high quality multi-planar reformations (MPRs) which can be used to generate an accurate center-lumen line as well as depiction of side branches. Black blood techniques have been superseded by CE-CMRA and non-contrast CMRA techniques. The latter technique is particularly useful because image acquisition is typically synchronized to the diastolic rest period which greatly improves evaluation of the aortic root and leads to sharper aortic wall delineation because there is no blurring due to vessel pulsatility Fig. . The advAnother important component of the aortic imaging protocol is measurement of flow. Although 2D flow sequences are still the most widely used technique, there is high interest protocols that allow determination of flow in a three-dimensional volume over the cardiac cycle . This can be particularly interesting in the chest since it enables simultaneous imaging of flow in the cardiac chambers as well as the large vessels in a single acquisition .2-weighted images display hyperintense signal in the hematoma, whereas signal is isointense on T1-weighted images. After approximately first 24 h, the IMH will appear hyperintense on both T1- and T2-weighted images. These features help differentiate IMH from mural thrombus, which appears hypointense or isointense on both T1- and T2-weighted sequences [cause of aortic hematoma and should be distinguished from ulcer-like projection, which is a consequence of the hematoma or thrombus in the wall, and only appear after an initial IMH [1- and T2-weighted sequences can demonstrate focal IMH as described above.Acute thoracic aortic syndromes include aortic dissection and limited intimal tear, intramural hematoma and penetrating aortic ulcer . Aortic equences . The useequences , 112. Petial IMH . Differe1-weighted bright blood, T2- and proton-density weighted black blood and 4D flow imaging was recently shown to be capable of depicting complex aortic plaque in the aortic arch and proximal descending aorta as well as potential embolization pathways from such plaques to the brain [CMR is also increasingly used to identify aortic atheroma as a potential source of cerebral emboli in cryptogenic stroke. A combined protocol using The brain .Carotid artery CE-CMRA is a highly reliable technique to depict the presence and extent of atherosclerotic plaque formation in the aortic arch branch vessels and to measure the degree of carotid artery stenosis . AdvanceAdvances in CMR hardware and pulse sequence design have enabled high-fidelity depiction of the pulmonary arteries and veins in short imaging times . The mosCE-CMRA remains the technique of choice for imaging the abdominal aorta and its branches. The ability to obtain high spatial resolution images of these vessels within a single breath hold enables accurate depiction of stenosis in the abdominal aorta, renal and mesenteric arteries . CMRA isFor many years CE-CMRA has been an accepted modality to depict the renal arteries. Renal artery CMRA is used to visualize the number and course of the renal arteries prior to nephrectomy and dynamic CE sequences can be added to the imaging protocol to quantify renal perfusion . HoweverCMRA has been shown to be a highly reliable technique to depict the presence and extent of arterial narrowing in patients with intermittent claudication and chronic critical ischemia –136. In Recently, significant advances have been made in non-contrast CMRA of the peripheral vessels. Promising results have been obtained with quiescent interval single shot (QISS) CMRA. In a study in 53 patients with suspected or known peripheral arterial disease the diagnostic performance of QISS CMRA was shown to be nearly equivalent to CE-CMRA and digital subtraction angiography . The samThe ability to null blood signal provides important opportunities for detection and characterization of vessel wall abnormalities with CMR. This does not only concern imaging of atherosclerotic plaque, but also inflammatory changes associated with vasculitis and rheumatological diseases. CMR vessel wall imaging has been shown to be capable of detecting, characterizing and quantifying atherosclerotic plaque in the aorta , 144, caIn patients with suspected or known large and medium vessel vasculitis, 3D fat-suppressed black-blood T1-weighted turbo spin-echo sequences have been of particular value to depict inflammatory changes such as post-contrast vessel wall enhancement in the aorta and its branches , extra- Early atherosclerotic changes in the arterial wall lead to outward remodelling and are not yet visible as luminal narrowing, which limits the utility of angiographic techniques. Pulse wave velocity (PWV) is a biomarker of arterial stiffness, which is known to increase long before the advent of stenosis. CMR is the technique of choice to measure PWV because it is a highly reliable for measurement of vessel length and vascular velocity waveforms at different locations in a vessel. The pulse wave can be understood as a wave superimposed on the flow/pressure waveform of the blood. This superimposed pulse wave accelerates and decelerates as it traverses distally in the vasculature relative to the stiffness of the vessel in a given segment . PWV is Another CMR based method to non-invasively assess vascular function is artery reactivity. Endothelial function can be examined non-invasively with stimuli which cause arterial vasodilation. Flow mediated dilation is used to examine endothelial function directly, by occluding usually the forearm using a blood pressure cuff inflated above systolic pressure for a standard time period. On release of the cuff, reactive hyperaemia causes increased endothelial shear and the release of nitric oxide which causes the brachial artery to dilate. Endothelial independent responses can also be tested by using glyceryl trinitrate, typically as a sublingual spray. Visualisation of brachial dilation with these stimuli was first described using ultrasound , but it The main indications for imaging the central veins are assessment of suspected anatomical variants and follow-up of patients with CHD , mappingBoth CE and non-contrast CMRA techniques can be used for depiction of the venous system. For imaging of chest veins non contrast cardiac triggered and respiratory navigator-gated bSSFP techniques can provide excellent image quality in short imaging times  and is oCoronary artery disease (CAD) spans a broad range of acquired and congenital coronary artery abnormalities. The vast majority of events such as myocardial infarction (MI) result from atherosclerosis. CAD may be further classified as ‘macrovascular’—involving the epicardial segments of the coronary artery tree—or ‘microvascular’ where vasomotor, neurohormonal and other factors affect the coronary microcirculation. CMR has proven utility in addressing most aspects of CAD, illuminating mechanism of disease and guiding the selection of therapeutic strategies Table .Table 3IPatients with acute coronary syndrome (ACS) have myocardial ischemia or injury resulting from disruption to coronary blood flow. Assessment of a standard 12-lead electrocardiogram (ECG) at presentation yields 2 broad categories of ACS: ST-segment elevation myocardial infarction (STEMI) and non-ST elevation events (NSTEMI). Classically, STEMI results from complete thrombotic occlusion of a coronary artery segment, whereas NSTEMI may represent subtotal occlusive or erosive CAD. Recognition of STEMI mandates rapid, uniform deployment of community-to-catheterization laboratory evaluation and management aimed at recanalization of the occluded coronary artery. No modality including CMR has shown compelling utility to support slowing down established pathways by adding imaging between presentation and coronary intervention. After invasive coronary angiography, however, CMR with its workhorse imaging technique of late gadolinium enhancement (LGE) affords in vivo visualization of myocardial injury, and hypointense regions within infarct scar indicate microvascular obstruction (MO). CMR may inform post-STEMI care when complicated by heart failure, arrhythmias, or LV dysfunction. The transmural extent of myocardial damage by LGE is inversely related to the likelihood of functional recovery, with even worse prognosis conferred with the presence of MO . T2-weigThese techniques can be used to test novel approaches to preserve myocardium in STEMI, such as optimal timing of stent placement in patients undergoing aspiration thrombectomy . IncorpoNSTEMI patients are more heterogeneous compared to STEMI not only in ECG findings but also in time course of presentation and revascularization. Importantly, NSTEMI comprise the vast majority of all ACS and may represent a greater opportunity for CMR to guide management. For instance, T2 imaging prior to invasive angiography in patients with NSTEMI has been shown to delineate myocardium at risk of irreversible injury, predicting both presence of CAD requiring revascularization as well as greater risk of adverse outcomes . Recent Symptomatic patients with known or suspected stable CAD may require evidence that symptoms are a result of CAD. Delineation of ischemic myocardium with stress myocardial perfusion imaging can guide coronary artery revascularization, targeting ischemic segments towards relief of symptoms Fig. . SeveralIn an era of more complex questions regarding native coronary artery or bypass graft anatomy amidst scarred vs viable myocardium, CMR has distinct advantages over other modalities. While single photon emission tomography (SPECT) may infer the presence of infarct scar in patients with ‘fixed defects’ e.g. reduced tracer uptake on both rest and stress perfusion images, having both LGE and perfusion imaging techniques allows CMR to better distinguish scar from hibernating myocardium .For individuals presenting in the acute setting with symptoms of intermediate CAD likelihood, stress perfusion CMR accurately identifies disease and safely facilitates discharge in patients with normal results, at lower cost when compared to standard inpatient evaluation with ICA .The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches, or ISCHEMIA trial, asked—how does routine invasive therapy improve outcomes compare to optimal medical therapy in patients with stable CAD and moderate to severe myocardial ischemia on noninvasive stress testing? While analysis from the small subgroup of subjects whose testing included stress CMR is underway, the overall trial results from over 5,000 patients randomized across 320 centers in 37 countries followed for a little over 3 years are relevant to today’s CMR practice. With a cohort of over three-fourths male patients with a significant burden of diabetes (41.8%), prior MI (19.2%) and preserved LV ejection fraction (LVEF) (median 60%), the primary outcome of cardiovascular death, MI, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure was similar among routine invasive (13.3%) and medical therapy (15.5%) groups (p = 0.34). These results endorse use of an accurate, cost-effective and noninvasive modality such as stress CMR in such patients in place of invasive evaluation.Myocardium may suffer infarction from causes other than obstructive CAD such as plaque erosion, spontaneous coronary artery dissection, coronary artery vasospasm, and coronary artery embolization. CMR is typically called upon after ICA has not provided a definitive anatomic abnormality, and when distinction of MI from myocarditis may be difficult by symptoms such as chest pain with biomarker evidence of myocardial injury. Occasionally, the angiogram is reviewed after CMR shows the classic signature of MI—subendocardial pattern of damage by LGE—and subtle invasive coronary angiography findings of erosive plaque or dissection are found retrospectively. In this setting, LGE unequivocally identifies the downstream myocardial damage as ischemic vs. inflammatory   making CDastidar and colleagues added significant evidence supporting CMR’s utility in both diagnosis and prognostic assessment in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) . CMR—incA contemporary understanding of coronary artery development sheds light on the range of anomalies that may result including anomalous connection, intrinsic abnormality such as non-atherosclerotic ectasia or ostial atresia, and anomalous myocardial/coronary artery interaction . While iOngoing and future clinical trials will hopefully illuminate novel CAD treatment approaches informed by CMR, particularly with mechanistically relevant endpoints to test efficacy.Kawasaki Disease is the prototypical systemic vasculitis that affects the coronary arteries. A disease with pediatric predilection, Kawasaki Disease typically presents with persistent fever and rash. Its potential for inflammation and aneurysm formation of the coronary arteries and ensuing myocardial damage typically mandates cardiovascular assessment, both acutely as well as in convalescence. CMR is ideal for comprehensive coronary and myocardial assessment in patients with Kawasaki Disease. Mavrogeni and colleagues offer a cogent summary of recommended CMR-based assessment during acute and chronic phases of the disease well-suited for techniques like coronary CMRA, functional assessment, perfusion with or without stress, and LGE imaging . A recenThese findings in a relatively rare disease are urgently relevant as the world struggles to respond to a Kawasaki Disease-like disease in children linked to the COVID-19 pandemic caused by severe acute respiratory syndrome coronary virus 2 (SARS-CoV-2) . SystemaThe cardiomyopathies are commonly understood as primary myocardial diseases, that are not caused by CAD, hypertension, valvular or CHD . ImportaCMR is widely accepted as the non-invasive gold standard for quantifying biventricular volumes, myocardial mass as well as regional/global systolic function . LV funcCMR is the most appropriate non-invasive method to assess tissue characteristics in vivo. The fundamental contrast-generating principle of CMR is rooted in the close relationship between the magnetic properties of tissue and its molecular composition. These predict the results of myocardial mapping and affect the signal intensity in standard CMR images. Standard CMR techniques include contrast-enhanced T1-weighted CMR after iv administration of contrast agents, typically GBCAs. These techniques have been successfully applied to visualize necrosis, scar, infiltration, inflammation, or intraventricular thrombi, while edema-sensitive T2-weighted CMR images can help identify acute injury . T2*-weiDilated cardiomyopathy (DCM) is characterized by ventricular dilatation, global systolic dysfunction and often accompanied by global myocardial fibrosis. CMR can accurately quantify volumes as well as regional and global LV function including wall thickening, and wall stress . RV voluCMR is regarded as the most useful non-invasive tool to assess for myocarditis . It addsLake Louise Criteria for CMR in Non-Ischemic Myocardial Inflammation recommend to assess them using T1-based and T2-based markers that detect myocardial edema and myocardial injury [The diagnostic targets of CMR include edema and an increased extracellular space caused by necrosis or scar. The recently updated l injury . Figure Increased signal intensity in T2-weighted imaging reflects inflammation-related myocardial edema , 237. PaThe hallmarks of hypertrophic cardiomyopathy (HCM) include an inadequate, mostly asymmetric increase of wall thickness and typically increased LV mass, associated with structural abnormalities, regional fibrosis, and LV outflow tract (LVOT) obstruction. All these markers can be quantitatively assessed by CMR. Myocardial wall thickness can be measured with more confidence than with TTE . Of noteIn HCM, the diagnostic workup can be significantly improved by CMR tissue characterization. Areas of marked hypertrophy often show regional fibrosis as focal areas with high signal intensity in LGE images , 248. FuAnother diagnostic target in the clinical phenotyping of HCM is the presence and hemodynamic relevance of LVOT obstruction. This can be assessed by planimetric evaluation of the LVOT area , a paramCMR is suitable for monitoring functional and morphological changes after therapeutic interventions . More reArrhythmogenic cardiomyopathy is a cause of sudden death, especially in young people. As it is associated with morphological and functional abnormalities of the RV, CMR is a preferred tool for adding diagnostic information to other known criteria derived from family history, ECG, and biopsies –261. WhiThe assessment of the RV is often complicated by large interindividual differences of the anatomy, its irregular shape and difficulties in visualizing the connected valves by standard views. As arrhythmogenic cardiomyopathy is also associated with fibro-fatty or fatty degeneration of the myocardium, many studies have attempted to establish new diagnostic criteria based on tissue alone. While areas with bright signal intensity have been described in the RV or LV free walls, RV wall tissue characterization has been notoriously difficult because of the thinness of the RV wall and the resulting susceptibility to partial volume effects, that render tissue characterization techniques unreliable.In patients with amyloidosis, cardiac involvement typically predicts their outcome. The main purpose of CMR therefore is the exclusion or confirmation of cardiac amyloid. While cine images are important to assess for the typical combination of concentric LV hypertrophy with reduced compliance and restriction, often combined with atrial dilatation and thickening of the valves and the atrial wall, the most important contribution of CMR is based on its ability to demonstrate tissue characteristics. The deposition of amyloid protein in the myocardium results in a marked increase of native myocardial T1  and to aSuspected myocardial iron deposition in patients undergoing repeated transfusions has become one of the most important applications of CMR, especially in geographical areas with a high incidence of thalassaemia, although this disease is now present worldwide due to immigration. As heart failure is the most frequent cause of death in patients with untreated iron overload, CMR can play a critical role in managing such patients. Because iron acts as a paramagnetic agent, its presence can be detected by its marked shortening effect on myocardial T2*. Since the introduction of this technique , the appLeft-ventricular noncompaction (LVNC) cardiomyopathy is characterized by LV dilatation, hypokinesis, and an abnormally high proportion of trabecular, non-compacted myocardium in combination with a thin compact wall. Initially described by TTE , the disAnderson-Fabry disease is caused by an enzyme defect leading to the accumulation of sphingolipids. Because the morphological appearance in myocardial involvement is indistinguishable from other forms of symmetric hypertrophy, the ability of CMR to identify sphingolipid storage in the myocardium has become a key diagnostic tool , 289. LiIn patients with pulmonary or extracardiac sarcoidosis, CMR should be used to verify or exclude myocardial infiltration and associated inflammation –295 as cStress-induced cardiomyopathy, also known as Takotsubo cardiomyopathy, is characterized by a reversible, extensive systolic wall motion abnormality, typically primarily involving the mid and apical LV , 301. AsEndomyocardial fibrosis leads to a mainly apical concentric wall thickening, caused by extensive subendocardial fibrosis, frequently associated with an apical intraventricular thrombus. CMR is used to assess for ventricular volumes , and systolic dysfunction. As a more specific finding, endomyocardial fibrosis can be verified by LGE images , 306. ThIn patients with suspected myocardial restriction, CMR assessment helps in verifying the diagnosis by demonstrating small ventricles in combination with enlarged atria –311. FurThe pericardium—a virtual, sub-atmospheric space under normal circumstances—can be the location and cause of significant cardiac morbidity and mortality. Standard cardiac imaging modalities such as TTE, not infrequently fail to adequately investigate this part of the heart. Other imaging techniques such as CT provide an excellent morphologic view on the pericardium but are limited to depict the hemodynamic impact on pericardial disease on the heart. CMR has evolved to one of the preferred modalities for pericardial imaging , 315. UsTogether with CT, CMR is likely the preferred modality to diagnose and to differentiate pericardial effusion. As CMR is not limited as echocardiography by the need of an adequate acoustic window, the entire pericardium can be satisfactorily investigated allowing to depict small or loculated effusions or to describe complex configurations , 315. TyInflammatory pericarditis can be isolated or part of systemic disease. TTE diagnosis relies on the depiction of pericardial effusion. However, many patients have no  or only physiologic amounts of pericardial effusion . As periPatients with pericardial inflammation, even relapsing forms, rarely evolve towards an end-stage constrictive pericarditis , 315. HiPericardial cyst is the most common pericardial congenital abnormality and is usually an incidental finding in asymptomatic patients , 315. AsPrimary tumours of the heart and pericardium, with the exception of atrial myxomas, occur rarely; metastatic tumors to or directly invasive of the heart are far more common , 329. InCardiac tumors produce a wide spectrum of symptoms through a number of mechanisms. Their size can obstruct intracardiac blood flow or interfere with valve function. Local invasion can lead to arrhythmias or pericardial effusions with tamponade. Fragments of tumor can embolize, causing systemic deficits when the tumors are on the left side of the heart and pulmonary infarcts on the right side. Finally, the tumors may cause systemic or constitutional symptoms. Some tumors, produce no symptoms and become evident as incidental findings.While TTE remains the first line imaging modality used in patients suspected of an intracardiac tumour or mass, this technique has several limitations and is highly dependent upon availability of good TTE “window” and even then, may not be able to provide a comprehensive answer due to limited field of view and inability to characterize tissue. Positron emission tomography (PET) can also be used to characterize cardiac masses, but it has limited availability and limited spatial resolution and only in combination with the anatomic information of CT has it become a valuable tool for a variety of oncologic indications . CMR hasFurther differentiation of the tumour can be made with GBCA which can be used in various ways –337. DurCrista terminalis, seen as a muscular ridge at the entry site of the superior vena cava into the right atrium, demarcating the part of the right atrium that is embryologically derived from the sinus venosus.Eustachian valve, variably present in the right atrium as a remnant structure, after conveying blood toward the foramen ovale during fetal life.“Coumadin ridge” at the confluence of the left upper pulmonary vein and the left atrial appendage which can sometimes be bulbous. This is easily recognized by CMR but it can sometimes be misinterpreted as a thrombus or mass particularly with TTE .Chiari network in the right atrium.The moderator band of the RV that uniquely identifies the anatomical RV;False tendons of the LV.Finally, it is important to recognize the difference between structures normally present in the heart, which may be mistaken as a cardiac mass, and true cardiac masses. Structures that are normally present in the heart but are sometimes misinterpreted as pathology are :Crista tCMR has unique capabilities which can greatly enhance the assessment of valvular heart disease. TTE will likely remain the first-line and most common imaging modality for assessing valve disease, and AHA/ACC and ESC guidelines recommend CMR when echocardiographic assessment is unable to provide sufficient information. However, there are many areas where CMR provides ‘added value’ to echocardiographic assessment in valve disease and can be complementary. Further, CMR can provide a comprehensive ‘stand-alone’ assessment in several situations, delivering optimal assessment of patients using a combination of techniques, and for some valve lesions it is the most accurate method of assessment Table .Table 7ICine CMR with bSSFP sequences provides high resolution imaging of valve anatomy and function, particularly utilising the high contrast between the valve leaflets and the blood pool Fig. . Care isPhase contrast velocity mapping delivers trans-valvar velocity, similarly to echo, with the advantage of not relying on alignment of the flow jet with the Doppler beam from the external chest wall Fig. . HoweverFinally, accurate and reproducible quantification of LV and RV volumes, mass and function using CMR allows assessment of the effect of the valve lesion(s) on each ventricle and can be monitored over time.Mild regurgitation is usually well assessed with echocardiography and in general does not require CMR assessment. The greatest utility of CMR lies in distinguishing moderate and severe regurgitation—this can be difficult with echocardiography, especially for aortic regurgitation and pulmonary regurgitation with eccentric jets, and also where valve anatomy is non-standard . Where discrepancy or uncertainty about the degree of regurgitation exists, CMR can usually provide a quantitative answer. Aortic regurgitation and pulmonary regurgitation are straightforward to assess with CMR, using phase contrast velocity mapping in a slice located just distal to the valve, and the regurgitant volume and regurgitant fraction (regurgitant volume/forward volume) can be quantified. It is important to use a reliable correction method for the background flow offset error that can occur, such as the interpolated background flow correction technique. Quantifying mitral regurgitation or tricuspid regurgitation is generally performed using an indirect approach, subtracting aortic flow or pulmonary flow (obtained from flow mapping) from LV or RV stroke volumes, respectively (using whole-heart volumetric cine assessment) . This teQuantifying aortic regurgitation with CMR has been shown to predict the future development of symptoms , and perCMR can assess any valve stenosis, although is most commonly used for aortic stenosis and pulmonary stenosis. This is best achieved with a bSSFP cine imaging slice at the valve tips in systole , which provides clear visualization of the degree of stenosis, and the valve area can be accurately measured from this , even wiVirtually all prosthetic valves and rings are safe in both 1.5 T and 3 T CMR scanners, and CMR assessment can be valuable where not adequately assessed by echocardiography. Most valves create a signal void artefact, although the degree is variable and depends on the type and amount of metal in the valve or frame. bSSFP or gradient echo cine imaging can visualize prosthetic leaflet opening in selected bioprosthetic valves, as well as demonstrate valve rocking, paravalvar leaks, abscesses and aneurysms where present. Flow quantification beyond the artefact from the valve can quantify forward velocity (for assessment of stenosis) and forward/reverse flow for regurgitation quantification, including the location of the leak. In selected cases, focused regions of interest for flow mapping can quantify the individual components of regurgitation  to aid clinical treatment decisions.CMR is one of the most powerful diagnostic tools in modern medicine and can provide highly reliable and actionable information for diagnosis and treatment across the spectrum of cardiovascular diseases. The high pace of technical advancements has led to a continuous expansion of the diagnostic capabilities and indications for CMR. In this Society for Cardiovascular Magnetic Resonance Consensus Panel report we provide a contemporary review of indications for CMR. The SCMR intends to update this document frequently with information about new CMR techniques and results of studies and trials that lead to new or altered indications for clinical CMR.


Primary immune thrombocytopenic purpura (ITP) is a common cause of thrombocytopenia. Due to the many possible precipitating factors, the diagnostic approach can be complex in nature. Much of the published literature on drug-induced ITP (DITP) report on quinine-induced thrombocytopenia. Here we present a case of the proposed dietary cause of DITP by the weight loss supplement Plexus® which contains two potential thrombocytopenia-causing compounds, garcinia cambogia fruit extract, and chromium polynicotinate. This case highlights how a thorough patient history, including evaluation of supplement use and dietary habits, can be of the utmost importance in the workup of ITP. Primary immune thrombocytopenic purpura (ITP) is an autoimmune disease caused by autoantibodies directed against platelet antigens, characterized by thrombocytopenia and increased risk of bleeding. Although the pathogenesis of the disease is not fully understood, it has been proposed that the pathogenic production of autoantibodies to the patient’s platelet membrane glycoproteins, specifically GPIIb/IIIa, is the primary pathologic feature of the disease ,2. The sOf specific interest to this report are the documented cases of secondary ITP induced by dietary compounds, categorized as drug-induced ITP (DITP). While being a relatively rare cause of ITP, dietary consumption of certain compounds is a well-reported precipitating event ,6. Most Here we report a related instance of a proposed dietary cause of DITP caused by the use of a common weight loss supplement, Plexus®. This supplement is a non-FDA approved drug marketed for weight loss and appetite suppression. Plexus contains both garcinia cambogia fruit extract, and chromium polynicotinate, both compounds hypothesized to be a potential cause of thrombocytopenia .A 30-year-old female, with a past medical history of polycystic ovarian syndrome and hypertension, presented to an internal medicine clinic for a chief complaint of “easy bruising” for approximately three weeks in duration. After complete blood count (CBC) and comprehensive metabolic panel (CMP) were completed, the patient was subsequently found to have a platelet count of eight-thousand and mild transaminitis with alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) of 99 and 63 respectively. She was immediately sent for hospital evaluation and admission. The patient endorsed mild bleeding of the gums after brushing her teeth over the past three weeks as well as two episodes of epistaxis during this same time period. The patient denied any pertinent family and surgical history. Additionally, she stated that she had never had easy bruising or a confirmed episode of thrombocytopenia before. The patient’s medications were Apri® (desogestrel and ethynyl estradiol) and Metformin daily. On questioning dietary habits and history the patient reported that six-eight weeks prior to this presentation she was taking Plexus-SLIM® as a weight loss supplement. The patient's review of systems was otherwise negative and she stated that she felt like she was in excellent health other than this current presentation of thrombocytopenia. On physical exam, vital signs were all within normal limits, and no abnormal findings were observed other than a petechial rash extending from the patient’s abdomen to the legs bilaterally. A chest X-Ray and abdominal ultrasound were done during hospital stay which revealed moderate cardiomegaly, and cholelithiasis without gallbladder thickening respectively. Additionally, an abdominal ultrasound revealed that the spleen was of normal size. A peripheral blood smear done during admission confirmed thrombocytopenia and revealed the presence of giant platelets, suggesting a mechanism of either peripheral platelet destruction or splenic sequestration. No schistocytes present on peripheral smear. The patient was tested for HIV, hepatitis B, and helicobacter pylori, all of which were negative. Additionally, a rheumatoid factor and antinuclear antibody (ANA) were ordered to test for the presence of autoimmune disease. These tests returned negative.With consideration of laboratory, radiologic findings, as well as physical exam the diagnosis of ITP was made. The patient was subsequently treated with Prednisone 100mg 1x daily and IVIG 1g/kg for two days. Over the course of three days, the patient’s platelets increased to 53 thousand. The patient was discharged on current prednisone dose with plans to gradually taper as well as follow up appointments in the clinic setting.The role of precipitating factors and inciting events has become an important aspect of the treatment and prevention of ITP. It has been observed and well reported that by means of molecular mimicry specific viral infections may play an important role as the inciting event of secondary ITP. Bacterial infections, such as helicobacter pylori, have also been shown to be a potential cause in a similar way to viral infections -11. It iWhile the potential causes of secondary ITP discussed above are the most common, they are by no means an exhaustive list and many other causes of ITP are reported in the current literature. Of these many reported causes of ITP, a small percentage are due to certain drugs and chemical compounds found in dietary supplements. Although multiple compounds have been reported we discuss chromium polynicotinate as well as garcinia cambogia extract as a possible cause for this patient’s presentation -17.Chromium polynicotinate has been thoroughly investigated for its potential to encourage weight loss and decrease appetite. Although, randomized trials have failed to prove its efficacy it is still ubiquitously used in many of the top-selling weight-loss diets and supplements . A case Garcinia cambogia is a fruit native to India and southwest Asia and contains the chemical compound hydroxycitric acid (HCA) which has been studied for its effects on weight loss appetite suppression . AccordiWhile it is a less common cause of thrombocytopenia, DITP represents an important subsection of ITP pathology that should be considered given the appropriate clinical scenario. Numerous reports are available in the literature suggesting a possible link between chemical compounds available in weight loss supplements such as Plexus® and DITP. While no definitive link has been made the need for further studies and observation is imperative. The importance of clinical suspicion in addition to a thorough patient history cannot be overstated and is crucial to the diagnosis of DITP.DITP is often a challenging diagnosis to make in the context of thrombocytopenia. While the pathology of ITP is often considered, deciding on a precipitating event is difficult and complex in nature. A thorough and complete history of the patient, including dietary habits, is a crucial diagnostic tool in the setting of thrombocytopenia. Additionally, increasing patient awareness of the potential dangers of non-FDA regulated supplements is an important aspect of patient education and overall patient care.


Taking care of Hemato-oncology patients in India, is one of the most resource intensive of all medical therapy. This takes up the maximum inpatient bed load, healthcare provider time and blood component resources of any hospital. The armamentarium necessary for management, includes all types of blood components, antibiotics, antifungals, chemotherapy; well trained staff ; financial, and social work support; all of which are often can be used in short supply. The lack of beds in most health facilities lead to admission delays, and over utilization of available space, thereby, increasing infection rates. The Coronavirus Disease-19 (COVID-19) pandemic, and subsequent national lockdown has severely affected the continuum of care. In a study from China, of COVID-19 positive patients , cancer patients were found to have a higher risk of severe adverse events compared with patients without cancer  . 9/L) will be at risk for rapid progression and severity of course . Cancer patients and immune-compromised patients will also continue to shed the virus for a longer period of time, this is extrapolated from data from Severe Acute Respiratory syndrome (SARS) and influenza . Hematopoietic stem cell transplant (HSCT) patients are at particular risk due to their prolonged and deep immune-compromised state. Hence non -essential HSCT are recommended to be postponed during the pandemic period. A risk being highlighted in the news and other media in many countries is the increased risk of acquisition of the infection from other patients or even infected health care providers. Guidelines recommend rational rationing of resources . In practice these are difficult and complex to implement. COVID-19 positive cases amongst those with new diagnosis of leukemia or other immune-compromised states with pre-existing lymphopenia, or prolonged neutropenia, will have a further increased risk of pneumonia, Acute Respiratory Distress Syndrome (ARDS) and prolonged viral shedding . It is important to note that lymphopenia is the most important risk factor for pneumonia and mortality of COVID-19 patients. The coronavirus infection appears to cause lymphopenia, hence patients with pre-existing severe lymphopenia . Acute myeloid leukemia patients should be treated in isolation rooms with excellent barrier nursing, with strict limits on visitors to reduce the risk of acquiring coronavirus infection during intensive chemotherapy. These patients need blood components like platelet apheresis, packed red blood cells and acute promyelocytic patients will need fresh frozen plasma and cryoprecipitate. Numerous challenges are being faced by diagnosed patients who are already on therapy. If the patient has disease in remission, or post hematopoietic stem cell transplant and can safely defer any follow up or therapy to decrease their risk of getting COVID-19; by avoiding hospital visits. However, this is resulting in confusion and repeated questions from patients because of different instructions which somewhat deviate from the standard instructions given earlier. Guidelines for patients on subsequent courses of chemotherapy for acute lymphoblastic leukemia for pediatric and young adults is unchanged, as the excellent survival should not be compromised. In older patients, dose modifications may be done if previous cytopenias occurred or are anticipated .Chronic Myeloid Leukemia (CML) therapy should also continue as per the pre COVID era. Patients should be advised to be compliant with their medicines and if stable can defer any upcoming molecular monitoring of BCR-ABL till a safer time. This will reduce the risk of infections and, therefore, treatment interruptions, which can cause progression to CML blast crisis, which at this point of time will be difficult to manage. The assessment of CML patients on wait and watch can be deferred. Patients can be monitored and treated with Intravenous Immunoglobulin (IVIG) and less cytotoxic drug Ibrutinib, where therapy cant be delayed. High risk myelodysplastic syndrome patients are immune-compromised due to their disease, hence therapy should not be delayed. These patients can be safely monitored and can receive Azacytadine at peripheral cancer clinics. They can also be advised erythropoietin or Thrombopoietin (TPO) receptor agonists to help decrease the need of frequent transfusion, which may be difficult. As much as possible transfusions should be taken close to the patients’ home. Prior to this crisis, patients would often travel across several State lines to receive transfusions at the tertiary care centers. Myeloproliferative neoplasm patients like primary myelofibrosis and polycythemia vera, again can be advised to continue medicines and be monitored via telemedicine. Patients on Ruxolitinib should be recommended to continue their medicine; cytopenia can occur in the initial 3 months of therapy and follow up by telemedicine and transfusion or dose adjustment for thrombocytopenia may be necessary. In patients of polycythemia vera, phlebotomy is a simple and important procedure and can be performed at district level hospitals.However, in case this is not possible, regular complete blood counts can be performed, then the patient can be put on hydroxyurea and monitored.Multiple myeloma auto transplantation can be deferred if the patient is stable, though some relapsed patients may require urgent treatment. Telemedicine can be appropriately utilized to monitor patients and advise continuation of medicines in patients who are on maintenance therapy. Regular laboratory monitoring at a local lab can facilitate this care and increase the confidence and comfort levels of care in both the doctor and the patient. Initial therapy can be stated with bortezomib, lenalidomide and dexamethasone (RVD). For multiple myeloma maintenance either RVD, continuing only Rd (reduction of dexamethasone dose to 20 mg or even 10 mg) in elderly patients. Hodgkins Lymphoma (HL) patients should receive full curative therapy, and avoidance of delays or modifications should be done as much as possible to ensure adequate chances of excellent cure rates. There has been some debate of whether Bleomycin should be omitted, but there is no consensus on this strategy. For early stage HL patients, reducing chemotherapy cycles and adding radiotherapy has been recommended, centers should see the situation of the pandemic and feasibility of coming daily for radiation therapy. Oncologists should decide to postpone, discontinue or modify radiation therapy for the patients undergoing or planned for it, keeping an individualized risk/benefit assessment in mind .Aggressive non hodgkins lymphoma patients like Burkitts, Diffuse large B cell etc. need urgent and standard therapy. There should be no compromise in dose intensity or medicines. Patients of indolent lymphoma can be recommended to review after the pandemic has subsided and can be on follow up and supportive care. Telemedicine practice has been approved, but refilling cancer medicines online is not approved in the new guidelines . Patients need to get a physical copy, though faxed or emailed prescriptions are now being allowed. This is a new process and every day poses new challenges to providers and patients. Even if patients are able to get prescriptions from us through daycare, Whatsapp or via email- many patients are unable to obtain medicines due to distribution problems, particularly in smaller towns. Teleconsultations are becoming an important tool to minimize disease related anxiety and stress among patients during this pandemic. Counselling by various doctors, nurses and social workers is now not encouraged to prevent the spread of infection. Delay or reducing intensity of therapy in patients of acute or chronic leukemias or myeloma patients  seems the right thing to do and is being advised by many society guidelines. Patients on follow up have to postpone checkups, miss long and difficult to obtain appointments for PET scan and other tests which may result in missing early relapse cases. Fortunately, as most hemato-oncology patients routinely wear masks, follow good hygiene practices and are advised to not visit crowded places. The interruptions in routine care have had an undesirable and tragic consequence on the outcome of non-COVID patients. There is a multi- fold increase in emergency room visits in Hemato-oncology cases. The cost of this pandemic on both hemato-oncology patients and doctors  is high. This pandemic is going to have long term serious consequences, and the oncologists must prepare for that in the coming time.


The aim of OA-INVOLVE is to provide recommendations to support older adult engagement in research that leads to the successful development of technologies for and with older adults. To support this aim we conducted a longitudinal case study project in which we interviewed eight AGE-WELL research teams conducting technology projects to explore the benefits, challenges, and solutions for meaningful engagement. Members of the OA-INVOLVE Older Adult Research Partner Group (OARPG) were involved in all aspects of the project. Findings from the case studies provided important insights regarding structural, contextual, and individual factors that enable and constrain active involvement of older adults. Many projects reported developing unique “workarounds” in order to move beyond involving older adults as participants to involving them as advisors and decision makers. Researchers identified that they often lack the skills, training and resources to engage older adults in a meaningful way and could benefit from capacity building.


We provide an update of the specific plant secondary metabolites that shape the microbiome, emphasizing newly discovered links between root chemistry and microbiome composition. One of the major questions in contemporary plant science involves determining the functional mechanisms that plants use to shape their microbiome. Plants produce a plethora of chemically diverse secondary metabolites, many of which exert bioactive effects on microorganisms. Several recent publications have unequivocally shown that plant secondary metabolites affect microbiome composition and function. These studies have pinpointed that the microbiome can be influenced by a diverse set of molecules, including: coumarins, glucosinolates, benzoxazinoids, camalexin, and triterpenes. In this review, we summarize the role of secondary metabolites in shaping the plant microbiome, highlighting recent literature. A body of knowledge is now emerging that links specific plant metabolites with distinct microbial responses, mediated via defined biochemical mechanisms. There is significant potential to boost agricultural sustainability via the targeted enhancement of beneficial microbial traits, and here we argue that the newly discovered links between root chemistry and microbiome composition could provide a new set of tools for rationally manipulating the plant microbiome. Historically, the vast majority of the literature on plant–microbe interactions studied a small set of nutrient-mobilizing symbionts and agricultural pathogens . HoweverMetagenomics surveys show that the number of enzymatic functions encoded in the microbiome vastly outweighs the enzymatic capability of the plant itself  effect, which can be caused by different mechanisms. Several recent studies have shown that secondary metabolites play a distinct role in fine-tuning the composition and function of the rhizosphere microbiome  (Lebeis p-hydroxybenzylglucosinolate has resulted in significant changes in the microbial community (Serendipita indica or Sebacina vermifera, which naturally colonize Arabidopsis roots (Colletotrichum tofieldiae, another naturally occurring colonizer of Arabidopsis, requires indolic glucosinolates for exerting its PGP effect, and at least some indolic phytoalexins to prevent it from turning into a pathogen (The glucosinolates are one of the best studied classes of defence compounds found in the Brassicaceae . These sAlternaria brassicicola and Botrytis cinerea, and the oomycete Phytophthora brassicae (On the other hand, the importance of camalexin, another sulfur-containing indolic phytoalexin, for shaping the root microbiome was revealed first by GWAS. Camalexin, 3-thiazol-2'-yl-indole, derived from tryptophan, is one of the major phytoalexins of Arabidopsis . CamalexGlucosinolates and camalexin are prominent examples of metabolites affecting microbiome assembly, because they are synthesized by the model plant Arabidopsis; however, they are specific to Brassicaceae. Another group of secondary metabolites that has been shown to shape the soil microbiota are the benzoxazinoids . They arLactobacillus strain that is able to absorb this metabolite (Pseudomonas simiae WCS417 (myb72 and f6′h1 mutants that do not secrete scopoletin (Pseudomonas strain can stimulate iron uptake in Arabidopsis (Another group of secondary metabolites involved in shaping the root microbiome are ubiquitous in the plant kingdom. Coumarins were first studied in the context of the human microbiome, because many health-promoting natural products as well as toxins belong to this class of metabolites. For example, feeding rats ochratoxin A, one of the major mycotoxins derived from a coumarin backbone, resulted in increased abundance of a tabolite , and alsTriterpenes are an abundant and ubiquitous class of secondary metabolites with known antimicrobial effects (One of the major questions in the field of plant–microbe interactions involves defining the functional mechanisms that plants use to shape their microbiome. This is a strategic priority, because these traits could be targeted in crop breeding programmes to develop more sustainable agriculture. Secondary metabolites have often been framed as a plausible mechanism for fine-tuning the plant microbiome, because these chemically diverse molecules frequently exhibit bioactive properties against microbes, and the extensive variation in metabolite profiles between plant species could explain some of the interspecies differences in microbial community assembly (There is now a rapidly expanding body of literature unequivocally showing that plant secondary metabolites affect microbiome composition and function . MethodoOver the next few years, we anticipate that further studies will continue to advance the mechanistic understanding of how secondary metabolites affect the microbiome. The existing literature has only scratched the surface of plant metabolic diversity, particularly because the majority of them are focused on Arabidopsis. Therefore, genetic manipulation of other metabolite biosynthesis pathways across diverse plant species is almost certain to generate plants with altered microbial associations. Furthermore, untargeted metabolomics measurements are becoming more widespread and accessible, with new approaches now enabling the integration of root metabolomic profiles with rhizosphere microbiome composition (In the longer term, it is tempting to speculate that secondary metabolites could be used as a tool for tailoring the plant microbiome. For example, breeding programmes could aim to rationally manipulate root chemistry by incorporating the entire biosynthetic pathway required to produce a targeted secondary metabolite, in order to recruit a beneficial strain or to deter a pathogen. To achieve this aim, one option could involve large-scale genome editing to introduce the necessary alleles into cultivated plants. Of course, efforts to move from discovery science to translation will probably encounter obstacles, particularly if the secondary metabolites which have the strongest influence on the microbiome were counter-selected during domestication and breeding due to their negative impact on palatability. Despite this, we still feel that secondary metabolites represent promising targets for rationally manipulating the plant microbiome, particularly because one of the selection pressures which favoured the evolution of these bioactive molecules was probably their capacity to influence the composition and function of the root microbial community.


Cancer affects millions of individuals worldwide. One shortcoming of traditional cancer classification systems is that, even for tumors affecting a single organ, there is significant molecular heterogeneity. Precise molecular classification of tumors could be beneficial in personalizing patients’ therapy and predicting prognosis. To this end, here we propose to use molecular signatures to further refine cancer classification. Molecular signatures are collections of genes characterizing particular cell types, tissues or disease. Signatures can be used to interpret expression profiles from heterogeneous samples. Large collections of gene signatures have previously been cataloged in the MSigDB database. We have developed a web-based Signature Visualization Tool (SaVanT) to display signature scores in user-generated expression data. Here we have undertaken a systematic analysis of correlations between inflammatory signatures and cancer samples, to test whether inflammation can differentiate cancer types. Inflammatory response signatures were obtained from MsigDB and SaVanT and a signature score was computed for samples associated with 7 different cancer types. We first identified types of cancers that had high inflammation levels as measured by these signatures. The correlation between signature scores and metadata of these patients  was then computed. We sought to evaluate correlations between inflammation with other clinical parameters and identified four cancer types that had statistically significant association  with at least one clinical characteristic: pancreas adenocarcinoma (PAAD), cholangiocarcinoma (CHOL), kidney chromophobe (KICH), and uveal melanoma (UVM). These results may allow future studies to use these approaches to further refine cancer subtyping and ultimately treatment. Many cancers are found when there is already local invasion or even distant metastatic disease. Among the issues complicating treatment options are the fact that there are many tumor types, whose response to therapy may differ depending on site of origin and cellular composition . Even wiAs a result, precise tumor classification is crucial; depending on the categorization of a tumor, the clinical course, prognosis, and treatment can vary dramatically . The traBy contrast, molecular classification is based on the analysis of tumor genomes as well as gene expression . SuccessHelicobacter pylori infection is associated with the majority of gastric cancer cases [Inflammation is of importance in the setting of cancer because chronic inflammation has been shown to increase cancer risk ,13 by caer cases .Several large consortia, such as The Cancer Genome Atlas (TCGA), provide tools and data to study the molecular basis of cancer ,22. The Signature visualization of individual samples allows identification of patient subcategories a priori on the basis of well-defined molecular signatures . As suchTo our knowledge, no systematic study utilizing gene signatures to evaluate tumor inflammation in TCGA has been carried out. Therefore, in this study, we aimed to use SaVanT to evaluate molecular signatures obtained from TCGA to evaluate the relationship between clinical status and inflammatory responses across multiple cancer types.In order to examine the role of inflammation in different cancer types, we sought to utilize a large-scale, systematically-processed dataset. We chose to analyze data from TCGA. All of the data has been processed with a uniform analysis pipeline, allowing for robust comparison across samples and tumor types. Gene expression data was retrieved from TCGA using their web-accessible data portal. In order to ensure that the data was normalized, we used their Harmonized Data Portal to access the data and did not include any datasets processed independently from the harmonized data. For all TCGA projects, we downloaded RNAseq data as normalized counts for all patients. Individual files (one per patient) were combined into a single matrix per primary site. In order to focus the evaluation of our methods, seven different tumor primary types were chosen to be utilized for analysis with clinical metadata–pancreatic adenocarcinoma (PAAD), glioblastoma multiforme (GBM), cholangiocarcinoma (CHOL), kidney renal papillary cell carcinoma (KIRP), kidney chromophobe (KICH), adrenocortical carcinoma (ACC), and uveal melanoma (UVM). We chose these seven out of the thirty-four tumor primary sites on TCGA, to obtain a range of inflammatory states estimated based on our analyses described below. Four types of metadata were retrieved for each sample: sex, age at initial cancer diagnosis, cancer stage, and vital status.All data retrieved from TCGA was inspected for consistency by making sure that all profiles contained the same number of genes and that patient data was not redundant or duplicated. Furthermore, the distribution of normalized counts was analyzed at both the patient level as well as primary tumor site to identify any outliers or issues with normalization. Patient-level data was averaged to determine a single value for all genes per primary site.Molecular signatures were taken from the repository MSigDB  and SaVaAveraged gene expression data from TCGA for each primary site was correlated with the hallmark inflammatory response signature through SaVant. Seven primary tumor sites were chosen as aforementioned. For each primary tumor site, each patient’s clinical metadata was compared with the corresponding p-value of correlation between their gene expression and hallmark inflammatory response. Metadata and corresponding statistical tests were utilized as follows–Age (Pearson correlation), Cancer Stage , Sex , and Patient Vital Status . Statistical significance was set at p < 0.05. Utilizing this data, box-whisker plots were created for metadata and inflammatory response correlations that had significant P-values. Box and whisker plots show distribution of p-values from correlation of individual patient data with hallmark inflammatory response.Hierarchical clustering was performed to group cancer subtypes by inflammatory signature scores, and the three subgroups were determined by the dendrogram structure resulting from the hierarchical clustering . Of the The full list of the 200 genes composing the Hallmark Inflammatory Response Signature, along with the hallmark annotations are published in full online . FurtherAfter associating the metadata of 181 patients with the hallmark inflammatory response signature in pancreatic adenocarcinoma samples, we found a significant association of the hallmark inflammatory response signature with sex (p = 0.0313) and tumor stage (p = 0.0054) . There wWe found a significant p-value of 0.0496  for the Using the signatures and metadata of 89 patients, we found a significant p-value = 0.0172  between After associating the vital status with the hallmark inflammatory response signature correlation of 80 patients, we found a significant p-value of 0.0033 . OverallUtilizing the TCGA database allows us to leverage the systematic profiling of thousands of tumors from individuals with different types of cancer. The first aim in our study was to evaluate levels of inflammation across tumor types utilizing appropriate signature scores. We used inflammation signatures to analyze the gene expression data  ,23–25. TOnce we compared the patient data to the inflammatory signatures, we found three distinct groups of cancers: (1) those with high inflammation, (2) those with low inflammation, and (3) those with both high and low levels of inflammation. We found PAAD to be a member of the high inflammation group. This grouping is supported by multiple studies associating pancreatic inflammation (pancreatitis) with the development of pancreatic cancer ,27. One We believe that the gene expression data for these tumor types is heterogeneous across individuals, with multiple subgroups of patients per type. As such, the inflammatory signature presented in this first analysis is averaged across individuals, and that within these broad categories there may be subgroups of patients with high inflammation and others with low inflammation. This suggests that patients with these cancers could potentially benefit from further molecular subclassification.In addition to correlating levels of inflammation with specific cancer types, we compared clinical metadata from individuals with 7 different types of distinct tumors with molecular signatures derived from the web-based tool SaVanT. Molecular signatures are gene collections with associated biological interpretations that can identify genes upregulated in specific sample subsets compared to broader groups . SignatuWe found that four of the cancer types we evaluated  had statistically significant associations between hallmark inflammatory response and at least one clinical variable. PAAD and KICH had a significant association with the patients’ cancer stage at time of diagnosis, and CHOL and UVM had an association with vital status. Additionally, PAAD was significantly associated with sex. On average, females and individuals with stage II PAAD had the highest correlation between the clinical variable and hallmark inflammatory response. While for KICH, the highest average correlation was for individuals with stage IV cancer. Within each cancer type, living individuals (at time of last data collection) with CHOL and dead patients (at time of last data collection) with UVM had the highest average correlation with hallmark inflammatory response. However, the correlation for both living and dead vital status individuals was higher for CHOL than UVM.By correlating inflammatory response hallmarks with patient metadata, our results indicate that there are statistically significant associations as detailed above. Our results from our preliminary investigation indicate a potential linkage between certain molecular subtypes of cancer and patients of different sex. Furthermore, the statistically significant linkage between hallmark inflammatory response and cancer stage for PAAD and KICH are suggestive of a linkage between certain tumor subtypes and aggressiveness of disease. The linkage between hallmark inflammatory response and vital status for CHOL and UVM was statistically significant. However, it is possible that certain subtypes of cancers could be associated with mortality rates of different time frames. Thus at a minimum, our results from our preliminary investigation indicate a potential linkage between the molecular composition of tumors and the clinical characteristics of the corresponding patients.The signatures provided by SaVanT supplement MSigDB utilize the depth and specificity of large expression studies to describe the biology pertaining to various cancers and cell types. The availability of this information for patients with cancer diagnoses could potentially facilitate a deeper understanding of a patient’s clinical status. Furthermore, as there is marked heterogeneity even amongst specific organ-based tumors , moleculIn order to expand upon our preliminary results, in future studies we aim to further evaluate the role of inflammation in cancer. Future studies should evaluate the relationship between additional tumor types with an expanded set of clinical variables. While we have shown three distinct groups of cancer types relative to inflammation levels, we also believe these results can be further honed and expanded. For example, limiting the number of genes in the signatures or creating a cancer-specific inflammatory response panel of genes could produce a more cost-effective diagnostic test to ultimately translate to the clinical setting.In addition, although many cancer types fall into the high or low inflammation classifications, there are others with a mixed inflammation signal. The ambiguity in this group of cancer subtypes could arise from several sources and correcting for these sources may allow us to place these cancers into either the high- or low-inflammation group. For example, the mixed signal could be due to the need to subclassify patients even further for a particular cancer type. It is possible that some primary sites contain several populations of samples–such as those from a different biopsy type . Determining these subgroups within the primary types would allow them to be treated independently.In summary, our study evaluated the association between inflammation signatures for various different tumor types. We found associations between levels of inflammation and tumor types, and also found statistically significant relationships between patient metadata and inflammation for four tumor types. We believe our results demonstrate the potential clinical utility in the continued establishment of personalized medicine and care for cancer patients, while further establishing the utility of SaVanT as a clinical tool.


As the number of people surviving beyond their 80s is growing dramatically, the prevalence of age-related neurodegenerative diseases is expected to almost double over the next 20 years, representing one of the major health challenges facing modern society. A common barrier to tackling these devastating diseases is that there are currently no drugs that slow down or stop their progression, and there is an urgent need for specific biomarkers that inform of disease evolution prior to symptom onset, when drugs are more likely to be effective.Recent technological advances have led to a gradual adoption of proteomic strategies to identify proteoforms involved in early disease pathways for use as drug targets and/or diagnostic markers. This collection of original research and review articles showcases how novel and state-of-the-art proteomics approaches such as Parallel Reaction Monitoring (PRM), Multiple Reaction Monitoring (MRM), Isobaric Tags for Relative and Absolute Quantitation (iTRAQ), Terminal Amine Isotopic Labeling of Substrates (TAILS), to name just a few, can be effective in identifying novel biomarkers and drug targets for the most prevalent neurodegenerative diseases, namely Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD).Barthélemy et al. report over 29 distinct phosphorylation sites in brain-derived tau and 12 sites in CSF-derived tau that showed variable abundance between AD patients and non-AD controls. This study is a strong example of how multiplexed quantification can be used to profile post-translational modifications that are otherwise undetected by standard immunoassays. These pathological species may prove valuable for improving AD diagnosis and tracking therapeutic responses in AD patients.AD represents the most prevalent neurodegenerative dementia  and specificity (93.7%) for AD.Reduced neuronal connectivity occurs early in AD Selkoe,  and can Lachen-Montes et al. combined iTRAQ labeling and transcriptomic analyses to study metabolomic changes in the olfactory bulb from the Tg2576 AD mouse model in a unique window of time that would not be possible using human subjects. They show that overproduction of human mutated amyloid precursor protein altered olfactory signaling in these mice even prior to the appearance of amyloid pathology. Survival kinome profiling revealed concomitant changes in the activation dynamics of two olfactory pathways with memory deficits and AD pathology. Both pathways were altered in postmortem olfactory bulb tissue from AD patients. By targeting a region that is affected early in AD, the authors identified two dysfunctional pathways, whose monitoring in living patients may improve early diagnosis and lead to novel therapeutic targets for AD.Smell impairment is another early event in AD  human embryonic kidney 293 cells have been used as internal standards to allow quantification of low-abundant proteins across control and FTD brain proteomes (Seyfried et al., FTD and ALS share common clinical, pathological, and genetic features (Ferrari et al., The aim of this collection is to stimulate conversation and advance research toward the prevention of these devastating neurodegenerative diseases. The collection highlights the wide range of technological strategies and source material available, each with its own advantages. These studies not only advance our understanding of the biological basis of these diseases, but also provide several promising avenues for that could improve diagnosis and disease management of the most common neurodegenerative diseases.OB, SL, ES, and CH edited this Research Topic and all contributed to the drafting of this editorial.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.


Although voice-activated assistants  have become smarter, faster, more personalized, and more ubiquitous, little is known about their potential to promote aging in place for people with disabilities. Partnering with Amazon’s Alexa team, a 2-month long design competition and hackathon was conducted to inspire college students to develop innovative voice-activated solutions to support successful aging with disabilities. This presentation will cover the specific inclusive experiences used to immerse student teams in the daily lives of the target population to ensure that design solutions responded to real needs of real people in real environments. These included: lectures on current research findings about the everyday needs and challenges of the target users as well as universal design approaches to solving those problems; a survey of individuals currently using voice-activated assistants to understand their benefits and potential uses; and providing target with Alexa-enabled devices and embedding them into the hackathon teams.


Sudden Unexpected Death in Epilepsy (SUDEP) is the leading cause of death in young adults with uncontrolled seizures. First aid guidance to prevent SUDEP, though, has not been previously published because the rarity of monitored cases has made the underlying mechanism difficult to define. This starkly contrasts with the first aid guidelines for sudden cardiac arrest that have been developed based on retrospective studies and expert consensus and the discussion of resuscitation challenges in various American Heart Association certificate courses. However, an increasing amount of evidence from documented SUDEP cases and near misses and from animal models points to a consistent sequence of events that starts with sudden airway occlusion and suggests a mechanistic basis for enhancing seizure first aid. In monitored cases, this sudden airway occlusion associated with seizure activity can be accurately inferred from inductance plethysmography or (depending on recording bandwidth) from electromyographic (EMG) bursts that are associated with inspiratory attempts appearing on the electroencephalogram (EEG) or the electrocardiogram (ECG). In an emergency setting or outside a hospital, seizure first aid can be improved by (1) keeping a lookout for sudden changes in airway status during a seizure, (2) distinguishing thoracic and abdominal movements during attempts to inspire from effective breathing, (3) applying a simple maneuver, the laryngospasm notch maneuver, that may help with airway management when aggressive airway management is unavailable, (4) providing oxygen early as a preventative step to reduce the risk of death, and (5) performing cardiopulmonary resuscitation before the limited post-ictal window of opportunity closes. We propose that these additions to first aid protocols can limit progression of any potential SUDEP case and prevent death. Risk stratification can be improved by recognition of airway occlusion, attendant hypoxia, and need for resuscitation. Sudden unexpected death in epilepsy (SUDEP) is a major cause of death among children and adults with epilepsy, particularly individuals whose seizures are poorly controlled e.g., , 2]. The. The2)].The Mortality in Epilepsy Monitoring Unit Study (MORTEMUS) identified a consistent sequence of events in epilepsy patients beginning with a generalized tonic clonic seizure and ending in death . CuratedThe goal of this review is to make first-responders look out for abrupt changes in airway status during a seizure and to offer preventative as well as interventional steps against the life-threatening consequences of obstructive apnea. First, we want to emphasize that a dangerous mechanism for the airway status to abruptly change from open to closed is internal, i.e., laryngospasm, making airway obstruction unexpected and thus potentially catching responders off guard. Second, we want to highlight the value of oxygen as a step that, when available early, protects against the consequences of obstructive apnea without actually influencing whether obstructive apnea occurs or not. Finally, we hope to raise awareness of the ictal and postictal sequence of events and time points for intervention in relation to the underlying mechanism so that efficacy of intervention steps can be optimized.Seizure first aid generally takes a “wait for the seizure to end” approach, emphasizing “care and comfort” first aid while remaining vigilant for uncommon severe features that would warrant a call for emergency help –21. Accohttps://www.epilepsy.com/learn/seizure-first-aid-and-safety/first-aid-seizures-stay-safe-side). First aid flowcharts for emergency departments are clear that cardiorespiratory compromise warrants oxygen as part of an active treatment .All seizure first aid protocols emphasize the importance of checking the airway and airway protection is emphasized in the “turn the person onto their side” guidance ] Respiratory derangements during seizures can be serious 2MSE study to evaluate the occurrence and degree of post-ictal hypoxemia and found that early administration of oxygen was associated with an early recovery of oxygen saturation and less frequent post-ictal EEG suppression. While they leave the issue of central vs. obstructive apnea as “an open question,” they do demonstrate value for early oxygen with completely independent metrics.The significance of seizure-associated hypoxemia as a contributor to death has been shown in a number of animal models, including rats , 23, 39,An important step in defining the mechanism of SUDEP came from differentiation of first-order, seizure-induced pathophysiological events from second-order consequences of these first-order derangements . This reLaryngospasm has been suspected during seizures in patients or observed postictally, based on findings of stridor and a narrowed airway when attempting to place an endotracheal tube  or intenIn persons who are monitored, seizure-associated airway occlusion can be accurately inferred from inductance plethysmography or (depending on recording bandwidth) electromyographic (EMG) bursts associated with inspiratory attempts appearing on the electroencephalogram (EEG) or the electrocardiogram (ECG). Evidence of significant hypoxia can appear as ST changes in the ECG or as EEG evidence of hypoxic seizure termination (decreasing amplitude with increasing frequency). With such data, individuals can be placed in a high-risk stratum that can be divided into three substrata when a seizure occurs with  evidenceFor clarification, some additional discussion of central vs. obstructive apnea and the issue of stertor as a source of EMG is warranted. Concepts such as post-convulsive central apnea (PCCA)  have beeWith regard to the EMG signal associated with respiratory effort, Vilella et al.  imply thMost healthcare facilities have emergency airway protocols and even difficult airway rapid response teams –64 to dehttps://www.youtube.com/watch?v=eIdWRYOQenQ).The vast majority of SUDEP cases occur outside a hospital where airway management is even more challenging. One option, not intended to substitute for the steps in an emergency airway protocol, but rather as a tool in the absence of hospital resources, is the laryngospasm notch maneuver . Often uBased on the recent recognition of obstructive apnea as the proximal cause of death during seizures, we propose three additions to the standard first aid algorithm for seizures. In contrast to the age-old emergency response teaching for patients having a generalized tonic clonic seizure—allow the seizure to terminate on its own prior to any airway-related interventions—we posit that the life-threatening consequences of obstructive apnea warrant immediate preventative and interventional measures during and after a seizure. At the same time, none of the proposed additions require manipulating the oral cavity of a patient having a generalized seizure, in keeping with the traditional rationale to protect both patient and responder from injury –21.Early oxygen protects against prolonged obstructive apnea and limits desaturation. In a rat model, access to an atmosphere enriched with oxygen approximately doubled the time between the onset of obstructive apnea and respiratory arrest  an understanding of what to expect will inform decisions about intubation and, more importantly, that (b) the laryngospasm will abate or can be broken with the laryngospasm notch maneuver to permit ventilation in cases where obstructive apnea is suspected.CPR alone, in or out of the hospital, can be sufficient. As discussed above, CPR was effective in all cases reported in the MORTEMUS study when applied within 3 min of respiratory arrest (y arrest . Such reThe three proposed additions are illustrated in A number of critical research questions remain, including how to help individuals at risk for SUDEP and their caregivers anticipate life-threatening events, and approaches to resuscitation that can be utilized anywhere. A greater understanding of the mechanisms by which seizures cause laryngospasm sufficient to completely obstruct the airway will also enable potential preventative strategies. One could argue, however, each two points:  that theAt this point in time, the best prevention is adequate seizure control , but we We believe that research on SUDEP has converged to permit an understanding of why early intervention with CPR has been successful in epilepsy patients and that vigilance with regard to assessing airflow and inspiratory effort can save lives, in spite of the sudden, unexpected occurrence of life-threatening airway obstruction.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.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.