Aug 18, 2022
On Episode 19 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two articles from the August 2022 issue of Stroke: “Direct to Angiosuite Versus Conventional Imaging in Suspected Large Vessel Occlusion” and “Recurrent Ischemic Stroke and Bleeding in Patients With AF Who Suffered an Acute Stroke While on Treatment With NOACs.” She also interviews Dr. Alexander Nave about “Combined Oral Triglyceride and Glucose Tolerance Test After Acute Ischemic Stroke to Predict Recurrent Vascular Events.”
Dr. Negar Asdaghi: Let's start with a few questions.
1) How much time do we actually save if we were to transfer all patients with suspected target vessel occlusion directly to the angiosuite and practically bypassing our current conventional imaging model?
2) What is the impact of an impaired metabolic state as measured by abnormal glucose and triglyceride tolerance tests on the risk of stroke recurrence in patients with ischemic stroke?
3) And finally, should we or should we not change the anticoagulant therapy of a patient with atrial fibrillation who suffered an ischemic stroke despite appropriate treatment with anticoagulation?
We have the answers to these questions and much more in today's podcast because this is the best in Stroke. Stay with us.
Dr. Negar Asdaghi: Welcome back to another issue of the Stroke Alert Podcast. My name is Negar Asdaghi. I'm an Associate Professor of Neurology at the University of Miami Miller School of Medicine and your host for the monthly Stroke Alert Podcast. The August 2022 issue of Stroke contains a range of really stimulating articles. We have an interesting study titled "Individual and Joint Effects of Influenza-Like Illness and Vaccinations on Stroke in the Young," led by Dr. Amelia Boehme and colleagues from Columbia University, with its accompanying editorial on how influenza-like illness is associated with increased risk of stroke in the young and middle-aged population while vaccinations of any type is protective of this risk. In a different paper, as part of a population-based study out of Scotland, Dr. Rustam Al-Shahi Salman from University of Edinburgh and colleagues report on a positive association between the use of beta-blockers, especially propranolol, and a lower risk of cerebral cavernous malformation, or CCM, associated intracranial hemorrhage. This study's findings are very interesting and quite important, and I encourage you to review the growing literature to suggest how beta-blockers may, in fact, reduce the risk of CCM-related hemorrhages through their anti-angiogenic properties.
Dr. Negar Asdaghi: Later in the podcast, I have the great pleasure of interviewing Dr. Alexander Nave from Charité University Hospital in Berlin to discuss the relationship between having an impaired metabolic state in the setting of acute stroke and the risk of ischemic stroke recurrence, as we'll review the long-awaited results of the Berlin "Cream&Sugar" study, a very catchy title. But first, with these two articles.
Dr. Negar Asdaghi: Time to successful endovascular reperfusion is an important predictor of clinical outcomes in patients with acute ischemic stroke related to a large vessel occlusion. And for years, we've known that the faster we're able to open the affected artery, the better the ischemic stroke outcomes are. Correspondingly, systems of care have adapted to various requirements of this so-called rapid workflow to ensure that all necessary pre-reperfusion steps are completed as fast as possible, preferably most in parallel to one another. And if any steps are unnecessary, they're bypassed altogether.
Dr. Negar Asdaghi: Despite all these modifications to date, time from conventional imaging to angiosuite arrival remains both the longest and the most variable interval in the intra-hospital workflow prior to endovascular therapy. So, it's not surprising that many recent studies have evaluated whether the current model of hospital arrival, then transfer to the scanner for imaging, then transfer to the angiosuite for endovascular therapy, can be replaced by a simpler model where, based on clinical assessment, a patient with high likelihood of having a target vessel occlusion can directly be transferred to the angiosuite, where fast stroke imaging, including CT, CT angiogram, and CT perfusion, are completed on the angiotable using the flat panel imaging technology.
Dr. Negar Asdaghi: If the patient is then found to be eligible to receive reperfusion therapies, including intravenous thrombolytics, they can receive the treatments and then proceed to endovascular thrombectomy without any further delays. So, in this issue of the journal, in the study titled "Direct to Angiosuite Versus Conventional Imaging in Suspected Large Vessel Occlusion," Dr. Raul Nogueira from Department of Neurology at Emory University and colleagues performed a systematic review and meta-analysis of published articles on this topic. So, they included seven articles for this analysis after pulling over 4000 articles using the common search engines for this meta-analysis. These articles included two single-centered European randomized controlled trials, one conducted in Germany, and the other one conducted in Spain, and five observational studies for a total of 1971 patients. The primary outcome was the odds of achieving favorable neurological recovery as defined by a modified Rankin Scale of zero to two at 90 days.
Dr. Negar Asdaghi: Now, a few things to note: All studies reported door-to-puncture times, but not all reported door-to-reperfusion times or rate of successful reperfusion, and we know that these metrics are important in predicting the odds of safety and efficacy outcomes of endovascular therapy. And also it's important to note that not all details of the safety and efficacy outcome measures were reported in all of those seven studies. So, with that, here are the main findings of the meta-analysis. First off, amongst patients who were directly transferred to the angiosuite across these seven studies, the overall rate of false activation was 28%, meaning that after imaging assessment, 28% of those who were directly taken to the angiotable were not found to have a target occlusion, and as such, there was no need to further proceed to endovascular thrombectomy. And this is a practical finding of this meta-analysis as we deal with resource allocation and concerns of potentially overwhelming the neurointerventional teams.
Dr. Negar Asdaghi: Now, moving on to the next finding of the study, the direct angio approach significantly reduced door-to-puncture times by a median of 30 minutes, and door-to-reperfusion times, when these metrics were available, by a median of 33 minutes as compared to the conventional imaging approach. So, bypassing conventional CT does translate into faster time metrics. These were, of course, expected findings of this meta-analysis, but nonetheless, important to quantify. But these faster time metrics did not improve the endovascular procedural outcomes, meaning that the direct to angio approach did not increase the odds of achieving a TICI 2b or better reperfusion, which is how successful reperfusion is defined, or the odds of achieving full reperfusion, meaning modified TICI 2c or greater reperfusion.
Dr. Negar Asdaghi: So, it's great to get to the angiosuite fast, but that does not impact the procedural outcomes of endovascular therapy. Despite the above, the faster approach resulted in a significantly better functional independence outcome as measured by mRS Scale at 90 days, again emphasizing how important time is when it comes to endovascular outcomes. Now, the authors also performed a number of subgroup analysis in this meta-analysis, which I'd like to highlight some of them. We know that the impact of time on endovascular outcomes is more robust in the early time window. So, not surprisingly, when restricting the primary outcomes to those presenting within six hours from symptom onset, the favorable effect of direct to angio approach persisted in the early time window as well.
Dr. Negar Asdaghi: Another important subgroup analysis was when restricting data to those patients who were transferred from a primary hospital to an endovascularly-capable center, the direct angio method didn't really have a significant impact on improving the primary outcome. Why is that? Let me repeat. So, when they restricted the analysis to those patients who were transferred from one hospital to an endovascularly-capable center, they did not find the same significant positive impact on endovascular outcomes in the direct to angio approach. I think the way we can explain this from a pathophysiological standpoint is that transferred patients are more likely to be slow progressors and, therefore, less likely to be impacted by delays in the workflow process as compared to the fast progressors.
Dr. Negar Asdaghi: Take-home message: We've got to be fast in the fast progressors, and it's safe to assume that those who are within the first six hours after presentation are more likely to be fast progressors, and these workflow modifications are, therefore, much more robust and much more impactful in patients who present early on after their symptoms onset. And finally, in terms of safety outcomes, there were no significant differences in the rate of symptomatic intracerebral hemorrhage rate or the 90-day mortality rates either for the whole study population or when the analysis was restricted to those treated in the early time window.
Dr. Negar Asdaghi: So, in summary, what we learned from this large meta-analysis is that as compared to the current conventional imaging model, the direct transfer to angio model is not only plausible and unlikely to overwhelm the interventional teams, as only less than 30% of patients in a direct method were not eligible for endovascular thrombectomy, but also this method is safe and results in significant improvements in workflow time metrics and functional outcomes. So, as the saying goes, select faster, select less, and treat more will likely be the future of endovascular therapy, particularly in the early time window.
Dr. Negar Asdaghi: We know that oral anticoagulants reduce the risk of ischemic events in patients with atrial fibrillation. Nonvitamin K antagonist oral anticoagulants, or NOACs, also known as direct oral anticoagulants, or DOACs, are currently the standard of care for treatment of patients with non-valvular atrial fibrillation. Now, we have to keep in mind that although NOACs reduce the risk of ischemic stroke and systemic embolism in atrial fibrillation, they don't completely abolish the risk. So, they're not curative treatments for AFib, and patients can still experience embolic events despite appropriate treatment with these agents. In a meta-analysis of randomized trials, the residual risk of ischemic events in patients treated with NOACs was estimated at 1.4% per year, but this number is a lot lower than what is reported by real-life observational studies.
Dr. Negar Asdaghi: In the large multicenter RENO study, which was published in this journal in 2019, we learned that in the setting of atrial fibrillation treated with a NOAC, a number of factors, including atrial enlargement, dyslipidemia, scoring high on the CHA2DS2-VASc score, and the use of low dose of NOACs, especially off-label low dose use of these medications, are significantly associated with increased risk of recurrent ischemic events despite treatment. But there's still a number of important questions that we routinely encounter in practice, most important of which is how to manage these patients with these so-called breakthrough ischemic events moving forward? Do we switch them to a different NOAC or go back to a vitamin K antagonist? Should we add an antiplatelet treatment to the regimen? And importantly, how do we counsel these patients and their families on their future risk of recurrent ischemic or hemorrhagic events?
Dr. Negar Asdaghi: So, in the current issue of the journal, the RENO investigators, led by Dr. Maurizio Paciaroni and Valeria Caso, set out to answer some of these important questions as part of the RENO-EXTEND study, which basically followed the patients in the RENO cohort for at least 12 months, evaluating them for either recurrent ischemic or hemorrhagic events, whether occurring intra or extracranially. So, a bit about this cohort. The RENO study was a multicenter observational cohort across 43 centers in Europe and the United States, including consecutive patients with atrial fibrillation who presented to the hospital with an acute ischemic stroke despite being on a NOAC therapy. Patients were enrolled in the study only if they were compliant with their NOAC treatment and they had not missed their treatment for any reasons for greater than 24 hours prior to their index event.
Dr. Negar Asdaghi: The patients were followed in the cohort and the choice of whether or not to start and timing, very importantly, for resumption of anticoagulation therapies were left to the discretion of the treating physicians. For the current paper, they analyzed 1240 patients. After the index event, 39.5%, so close to 40%, had their NOACs changed to another NOAC, mostly to a different class of NOAC. 42.5% continued with the same NOAC at the same dose. 6.7% continued with the same NOAC, but the dose was increased, and a small percentage were shifted to warfarin, that was only 4.7% of the patients. And 6.6% were shifted to low molecular weight heparin or were never prescribed oral anticoagulations after that index event for a variety of reasons, such as earlier ischemic recurrence, early hemorrhagic transformation, or early death or severe index stroke. And the overall median follow up in the study was 15 months.
Dr. Negar Asdaghi: So, with that, here are the main study findings. The annual rate of the primary outcome of recurrent ischemic or hemorrhagic events, again, a reminder that these could have been intra or extracranial events, was 13.4%. The majority of these events were ischemic stroke, followed by major extracranial bleeding, then intracranial bleeding and systemic embolism. We have to note that this overall primary outcome rate is a lot higher than what was observed as part of the randomized trials of NOACs, as we noted earlier, which is an important finding of these real-life studies. Now, with regards to the factors predicting the primary outcome, having a higher CHA2DS2-VASc score and persistent hypertension were both predictive of recurrent ischemic events, whether ischemic stroke or systemic embolism. Next, the predictive factors for hemorrhagic events, either intracranial or major extracranial bleeding, included age, for each year increase in age, the odds increased by 1.1; history of major bleeding in the past; and, very importantly, a scenario that not uncommonly happens in routine practice, which is the addition of antiplatelet to a NOAC after the so-called NOAC failure.
Dr. Negar Asdaghi: And finally, it turns out that changing that failed NOAC to a different agent didn't really seem to make a difference at all. As we mentioned earlier, close to 40% of patients were changed from one NOAC to another agent after the index ischemic event, and when they looked at the primary outcome, there was no difference in the rate of combined ischemic and hemorrhagic events, or the ischemic events alone, or bleeding outcomes alone, amongst patients who changed their NOAC to a different agent as compared to those who did not. The authors performed a number of subanalyses to see whether a particular strategy, for example, a switch from a particular class of NOACs to another class, or change in dosage, or NOAC to warfarin change, may be more or less beneficial in reducing the primary outcome, and there was really no difference between any of these strategies with the exception of one group.
Dr. Negar Asdaghi: It turns out that the cumulative risk of ischemic and hemorrhagic events were a lot higher in those 6.6% of patients in whom NOAC treatment was changed to low molecular weight heparin injection. But I think one should consider this observation as hypothesis generating. First off, it was just a very small percentage of patients in this study that actually did go through this switch. And also we should note that in practice, we reserve a switch to low molecular weight heparin injection in only special cases. Some examples would be patients in whom there's a consideration of a hypercoagulable state, whether cancer related or not. But regardless, I think what we learned from this finding is that the patients in whom low molecular weight heparin injection is considered after a NOAC or an anticoagulant failure are likely very high risk patients for recurrent thromboembolic and hemorrhagic events.
Dr. Negar Asdaghi: So, in summary, we learned a number of important lessons from RENO-EXTEND study. Number one, patients with atrial fibrillation presenting with a breakthrough ischemic stroke, despite treatment with NOAC, represent a high-risk group of patients who continue to be at a substantial risk for recurrent events, mostly ischemic, but also hemorrhagic. And this substantial risk was actually over 10% in the current study. Number two, we also learned that various strategies of changing the dose or class of anticoagulants don't seem to have much, if any, benefit in reducing the recurrent event outcomes. And finally, the addition of antiplatelet to oral anticoagulant therapies in this situation is not a good idea. This strategy gets us more in trouble and can increase the risk of bleeding and confers practically no benefits. Finally, these are the types of patients in whom we may have to consider other treatment options, such as left atrial appendage closure, and I'm sure we'll hear more on this in the future.
Dr. Negar Asdaghi: Having an abnormal lipid profile has long been recognized as a risk factor for development of vascular disorders, particularly leading to atherosclerosis, but this association varies for the different components of the lipid panel and is most robust for elevated low density lipoprotein cholesterol levels, or LDL, causing various vascular disorders. Amongst patients with ischemic stroke and TIA, randomized trials have also shown that lowering LDL can reduce the risk of major cardiovascular events, including the risk of ischemic stroke, but the connection between elevated triglyceride levels and the risk of recurrent ischemic stroke is less clear. Moving from lipids to sugar, the presence of uncontrolled diabetes increases the risk of stroke by two to five folds, depending on the patient population studied and coexistence of other risk factors. In contrast, impaired glucose tolerance, which is an intermediate metabolic state between normal glucose tolerance and diabetes, has also been found to be associated with an increased risk of stroke in patients with coronary artery disease, but this association is less clear amongst patients with ischemic stroke.
Dr. Negar Asdaghi: In clinical practice, fasting blood glucose and lipid profiles are routinely measured post-stroke, but we put a greater emphasis on the elevated LDL and hemoglobin A1C levels, and, in general, pay less attention, if any, to other metabolic derangements, including the impaired glucose tolerance state or even abnormal triglyceride levels. So, the question is, what is the impact of these metabolic derangements on the risk of stroke recurrence amongst patients presenting with ischemic stroke? In the current issue of the journal, in the study titled "A Combined Oral Triglyceride and Glucose Tolerance Test After Acute Ischemic Stroke to Predict Recurrent Vascular Events: The Berlin 'Cream&Sugar' Study," we learn about these important associations. Joining me now is the first author of this paper, Dr. Alexander Nave. Dr. Nave is a neurologist and clinician scientist at Charité University Hospital in Berlin. He leads a junior research group as part of the Center of Stroke Research in Berlin and has a special interest in stroke rehabilitation and cardioembolic risk factors of stroke. Good morning, Alex, from Miami. Good afternoon to you in Berlin. Thank you for joining us. Welcome to our podcast.
Dr. Alexander Nave: Hi, thank you very much. I'm very happy to be with you.
Dr. Negar Asdaghi: All right. Let's go over the background of what we knew on the association between elevated triglyceride levels and the risk of recurrent stroke.
Dr. Alexander Nave: Sure. So, as you pointed out earlier, diabetes and hypercholesterolemia are well established risk factors for first and recurrent ischemic stroke. However, for triglyceride levels, this association is less well understood and somewhat inconclusive. So, prior large epidemiological studies of the healthy population from the U.S. and from Denmark have shown an independent association of triglyceride levels in the risk of vascular events, including ischemic stroke. This association was actually stronger for non-fasting triglycerides levels compared to fasting triglycerides levels. In the ischemic stroke population, however, there were only a few investigations with conflicting results. So, the SPARCL trial, for example, which was a large secondary prevention stroke trial with more than 3000 stroke patients, showed that triglyceride levels were associated with major cardiovascular events, but not with recurrent ischemic stroke. So, therefore, we designed the Berlin “Cream&Sugar” study to investigate the association of postprandial triglyceride levels following an oral triglyceride tolerance test with recurrent vascular risk.
Dr. Negar Asdaghi: So, let me just summarize. From SPARCL, actually, we knew that an increased level of triglycerides were associated with increased risk of development of cardiovascular events, so things such as coronary artery events and so on, but not an increased risk of stroke. And that's where you come in with the new study, the Berlin “Cream&Sugar” study. Now, before we talk about the study, can you tell us a little bit about the tests that were done, the oral triglyceride and glucose tolerance tests?
Dr. Alexander Nave: Absolutely. So, both tests eventually help us to evaluate the glucose and lipid metabolism of a patient. So, the OGTT, the oral glucose tolerance test, as most of the listeners probably know, is a test that helps us to assess the ability of the patient to metabolize glucose after receiving a drink with a standard dose of 75 grams of glucose. The blood glucose levels after one hour and two hours then help us to diagnose diabetes or pre-diabetic state of the patient. So, we're not only evaluating the fasting state, but we can also quantify the body's response to a glucose challenge. And as an equivalent, the OTTT, the oral triglyceride tolerance test, will test the ability of a patient to metabolize triglycerides after oral ingestion of a lipid challenge, which is usually a certain amount of fat. However, this test is less well studied and without any standardized diagnostic criteria so far. And in contrast to the OGTT, the OTTT has not been tested in the stroke population so far.
Dr. Negar Asdaghi: So, we're not just looking at those metrics of fasting sugar or fasting lipids and triglycerides specifically, we're looking at the patient's ability to metabolize glucose or triglyceride levels. So, now, with that understanding, can you tell us a little bit about the methodology of the study?
Dr. Alexander Nave: Yes, of course. So the Berlin “Cream&Sugar” study was a prospective observational study recruiting acute stroke patients between 2009 and 2017 at the Charité University Hospital in Berlin. And we included first-ever ischemic stroke patients within three days to seven days after onset of stroke, and all patients received a sequential OTTT OGTT. So, all recruited patients received fasting blood sampling in the morning before taking the OTTT with 250 cc of cream, which corresponds to 30% of fat intake. So, all patients without known diabetes mellitus additionally had the OGTT with 75 grams of glucose starting three hours after the OTTT.
Dr. Alexander Nave: And all patients received consecutive blood tests at three hours, four hours, and five hours after start of the OTTT to determine the course of glucose and triglyceride levels in the blood. And after one year, we performed follow up of all patients. The primary outcome was recurrent fatal or non-fatal ischemic stroke, and secondary outcome was a composite endpoint of recurrent vascular events, including ischemic stroke, TIA, myocardial infarction, and coronary revascularization, as well as cardiovascular death. And we compared patients with high versus low fasting and nonfasting triglyceride and glucose levels, respectively, using Cox regression analysis.
Dr. Negar Asdaghi: Okay. 250 cc of cream and 75 grams of sugar right after a stroke. Was it challenging to recruit patients?
Dr. Alexander Nave: Yes, that was a task. And we did experience some difficulties during the course of the study. It was not easy to ask a patient to drink a glass of cream during the first week after suffering from a stroke, obviously. In fact, a substantial number of patients eventually did not participate or did not complete the OTTT. However, in our study, we showed that performing a sequential OGTT OTTT within seven days after stroke was feasible. Approximately 10% of patients reported only minor adverse events such as nausea, diarrhea, and bloating. But with regards to the study population, overall, we enrolled 755 patients, 523 have completed the challenge and entered follow up. So, considering the fact that we had some difficulties in recruitment, was not surprising that we predominantly ended up with minor ischemic stroke patients, considering that we did not include patients with dysphagia or patients that were not able to give informed consent in the early phase after stroke. The median NIHSS was one with an interquartile range of zero to three. And, as I mentioned previously, this was because patients with impaired swallowing could not be included into the study.
Dr. Negar Asdaghi: Okay. So, 750 patients within a week after their stroke, majority of them, as you mentioned, had mild ischemic events, were enrolled, and then they underwent sequential OTTT and OGTT tests. And then they were followed for a year for the primary outcomes. Now I think we're ready to hear the primary results.
Dr. Alexander Nave: Sure. So, overall, 54 patients, 10% of the total population, reached a study endpoint within one year follow up. 31 patients experienced recurrent ischemic stroke within one year. So, when we compared the highest quartiles of triglyceride levels to the lowest quartiles, neither fasting nor postprandial triglyceride levels were associated with recurrent stroke. Similarly, fasting triglyceride levels were not associated with major cardiovascular events one year after stroke. Surprisingly though, higher postprandial triglycerides, measured at five hours after OTTT, were significantly associated with a lower risk for recurrent vascular events. The hazard ratio was 0.42, and the confidence interval 0.18 to 0.95. So, regarding glucose levels, on the other hand, we found no associations between glucose levels and recurrent vascular risk at all.
Dr. Negar Asdaghi: Interesting. So, before I ask you what your takeaway is from all of this, the first question is the 10% rate of primary outcome. Were you at all surprised by this? This seems quite high for the recurrent rate of vascular events after the first year after ischemic stroke and TIA.
Dr. Alexander Nave: Well, actually, when the “Cream&Sugar” study was designed, we expected the recurrent event rate to be even higher, approximately 10% of recurrent stroke events within one year and not 10% recurrent vascular events as a composite outcome. But as we know from previous registries, such as the TIA registry, the recurrent risk of vascular events after TIA and minor stroke is much lower now. So, I think with the reported 7% of recurrent stroke events, we're actually quite in line with the reports of the TIA registry, considering the fact also that we had no TIA patients enrolled in our study and had quite a high proportion of patients with large artery atherosclerosis as well as atrial fibrillation.
Dr. Negar Asdaghi: So, thank you. This is a grim reminder that ischemic stroke patients remain at high risk of having recurrent vascular events. Alex, what should be our top two takeaway messages from your study?
Dr. Alexander Nave: So, first, I think a sequential OTTT OGTT probably does not contribute a lot to future vascular risk stratification in ischemic stroke patients. So, I think all patients and carers can be relieved. There's no need to implement an OTTT into routine clinical care. However, based on our results, I think further studies are necessary and needed to better understand the importance of glucose and lipid metabolism in patients after acute ischemic stroke. And eventually we might figure out some nice information how we can improve risk prediction.
Dr. Negar Asdaghi: So, it's good to know that we don't have to ask patients to drink a lot of cream after stroke. Can you tell us a little bit about the future of the Berlin “Cream&Sugar” study group? What are the next steps for the authors and the study group?
Dr. Alexander Nave: Absolutely. Well, since there's no urgent need to start another large study soon, I think it would be reasonable to get our data and merge it with datas from other groups who also investigated the role of an OTTT in cardiovascular risk cohorts, also to increase power and detect some other signals. And we want to have a more detailed look at the variability of triglycerides and glucose levels following sequential OTTT OGTT. So, not only go into the absolute levels that you can measure at certain time points, but also how much these parameters fluctuate over time.
Dr. Negar Asdaghi: To Alexander Nave, it's been a pleasure interviewing you on the podcast today. We look forward to covering more of your work in the future.
Dr. Alexander Nave: Thank you very much. It was a pleasure to talk to you.
Dr. Negar Asdaghi: And this concludes our podcast for the August 2022 issue of Stroke. Please be sure to check out this month's table of contents for the full list of publications, including three topical reviews, from “Strategies for Maintaining Brain Health: The Role of Stroke Risk Factors Unique to Elderly Women” to “Ethical Considerations in Surgical Decompression for Stroke.” These articles summarize a large body of evidence, which I encourage you to review. And before we end our August podcast, I'd like to take a moment to recognize the incredible dedication and hard work of our medical students and fellows, especially the young doctors who are just starting their training this year.
Dr. Negar Asdaghi: And if you happen to be one of those young doctors who is listening to our podcast in one of those sleepless on-call nights, I want to recount the story of Dr. Carl David Anderson, who won the Nobel Prize in physics for his discovery of the first particle of antimatter known as positron on August 2, 1932. A positron is actually the identical twin of the well-known negative electron, and its discovery in the 1930s truly changed our understanding of the origin of the universe, and it's practically impacted all aspects of science, not to mention it's impacted medicine and medical imaging. But the moral of the story lies in the fact that on August 2, when Anderson announced his discovery, he was a post-doctoral fellow himself, hadn't even graduated yet. So, if you are such a trainee, I hope you know that your hard work, combined with that incredible scientific inquisition, has the potential to change our understanding of the universe. And what better way to do this? You guessed it, than staying alert with Stroke Alert.
Dr. Negar Asdaghi: This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit AHAjournals.org.