The American College of Cardiology's 70th Annual Scientific Session & Expo will be held virtually May 15-17, 2021. ACC.21 will provide practice-changing research and cutting-edge education.

Coverage of the American College of Cardiology Conference Is Coming

ATS 2021 will be held virtually May 14-19, 2021. The meeting will include latest advances and discoveries in respiratory science, patient care and global respiratory health.

Coverage of the American Thoracic Society Conference Is Coming

Virtual ISPOR 2021 will be held May 17-20. This year's meeting, themed "HEOR: Evolving for Tomorrow’s Challenges," will analyze opportunities and challenges in health economics and outcomes research methods, practices, and application.

Coverage of the Virtual ISPOR 2021 Meeting Is Coming

If 2020 was dominated by the news of how COVID-19 spread across the globe, then 2021 has so far been focused on ending the pandemic through vaccine distribution.

A Timeline of COVID-19 Vaccine Developments in 2021

We interview experts on investigational treatments such as liso-cel, and ask how to bring them to community practice.

Spotlight on CAR T-Cell Therapy

The American Journal of Accountable Care® features research and commentary on new payment models.

New Members for AJAC Board

Patients with hypertrophic cardiomyopathy (HCM) had symptomatic, functional, and structural biomarker changes over the course of a little over 6 months. Mavacamten reduces the hypercontractile state of the heart by resetting the myosin heads back to a normal state, explained Jay Edelberg, MD, PhD, head of Heart Failure and Cardiomyopathy Development at Bristol Myers Squibb.

Data on mavacamten (Bristol Myers Squibb) from the EXPLORER-HCM trial were released earlier today during the session, “Health Status Benefits of Mavacamten In Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy: Results from the EXPLORER-HCM Randomized Clinical Trial,” at ACC.21, the 70th Scientific Session from the 

Can you briefly discuss the phase 3 EXPLORER-HCM data on mavacamten?

So we're really excited about what EXPLORER did for our patients. We enrolled patients who have the symptomatic form of obstructive hypertrophic cardiomyopathy, and we enrolled 251 patients who were randomized to receive mavacamten or placebo over the course of 30 weeks. What we saw was really exciting.

Our patients had symptomatic, functional, structural biomarker changes, all with mavacamten treatment, over the course of a little over 6 months. Their New York Heart Association class improved, their patient-reported outcomes improved, their exercise capacity as measured by peak VO2 and other measures improved. Their gradients were markedly reduced. Other important parameters improved. Their biomarkers of wall stress and injury all improved.

We're really excited about what this means for our patients.

How does the mechanism of mavacamten work to modulate cardiac myosin and regulate hypercontractility?

So with HCM, the heart is basically in a hypercontractile state for much. The engine of the heart, the sarcomere, has too many of its myosin heads engaged. It's basically working overtime all the time, and that leads to hypertrophy and ill effects for our patients. This is due to genetics for the most part. Too many of the myosin heads are engaged.

What mavacamten does is it helps to reset them back to a normal state so the heart can increase when it needs to but is back into that normal state of myosin head engagement. And this translates to our patients by being able to reduce that hypercontractility. Therefore, the dynamic gradient is reduced and our patients are feeling better, and they're functioning better.

Why is it important to treat the actual mechanism of obstructive HCM vs the symptoms?

So with HCM, especially with obstructive forms of the disease, what we see is this is a dynamic outflow tract obstruction. We can see this gradient and these symptoms exist at rest. And it can get worse when patients exercise. And so the mainstay of the therapy has really been about preventing the hearts from actually exercising in the first place, basically getting beta-blockers to limit the ability of the heart to increase its rate.

With mavacamten, what we're doing is we're targeting the cause of the disease with the sarcomeric state, which allows the heart to get back to a normal function. And so our patients are able to relieve their gradient and improve their symptoms and improve their function—basically resetting where the heart was. We're not trying to simply mask the symptoms by blunting the heart rate. We’re trying to treat the disease.

What have we learned about mavacamten since the phase 3 results were released last August?

Well, what we're reporting here at the American College of Cardiology is the continued benefit we're seeing in our patients here. We'd had good results in the PIONEER phase 2 study and the continuation of those are our open-label extension. With EXPLORER, we continued to treat all the patients—those who were both on drug as well as on placebo—in a long-term extension. We've seen that those results demonstrate that our patients continue to get benefit. The symptoms and the overall structural changes, the biomarkers, are all improved. The effects of mavacamten are durable when we continue to study them.

We're also seeing results of the expanded analysis of the patient-reported outcome, KCCQ [Kansas City Cardiomyopathy Questionnaire], showing all elements of the KCCQ. How patients are feeling have been improved, with some patients getting really dramatic improvements. They're demonstrating what we knew: that mavacamten is helping our patients to really feel better. And now we can see that it's actually doing it long term.

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Patients with hypertrophic cardiomyopathy (HCM) had symptomatic, functional, and structural biomarker changes over the course of a little more than 6 months, explained Jay Edelberg, MD, PhD, head of Heart Failure and Cardiomyopathy Development at Bristol Myers Squibb. 

Dr Jay Edelberg: Mavacamten Is Producing Exciting Long-term Results in HCM 

Pharmacy Quality Alliance (PQA) 2021 Online Annual Meeting

 discussed the public health challenge of diabetes and the role that pharmacies and pharmacy quality measures can play.

Diabetes prevention programs (DPP) can assist individuals in making lasting behavioral changes in order to halt a slide to type 2 diabetes (T2D), a report from 

 noted. Panelists from Tabula Rasa HealthCare spoke about their DPP, which involves on-demand digital, telehealth, and a participant portal; the goal is to nudge participants to lose 5% to 7% of body weight through weekly and monthly sessions with a lifestyle coach.

Focusing on preventing costly diseases in the first place will help lower the overall cost of care, they note.

Also at PQA, a Walgreens executive discussed how the pharmacy chain is attempting to address social determinants of health on the South Side of Chicago with interventions aimed at addressing gaps in care in diabetes.

A diabetes outreach program uses predictive analytics and selects patients based on their adherence patterns, according to Michael Taitel, PhD, senior director of health analytics, research, and reporting at Walgreens.

, the program has addressed disparities in diabetes care, leading to significant improvements in adherence, statin use, and flu vaccinations among patients with diabetes.

In the 16 stores that implemented interventions, there was a 2.1% improvement in the percent of diabetes prescriptions being refilled within 2 weeks of their due date, compared to no improvement in stores that did not implement the program. Similarly, the test stores saw a 3.4% improvement in the percent of statin prescriptions refilled within 2 weeks of their due date, and a 25.0% improvement in the number of flu vaccinations administered at the pharmacy.

Articles

There is a role for pharmacists and pharmacy quality measures in addressing the public health challenge of diabetes, according to speakers at a recent virtual meeting this week.

Diabetes in the News: PQA Speakers Focus on Prevention, Gaps in Care

ADAPTABLE was an opportunity to accomplish a large-scale study in a generalizable manner: directly involve patients, partner with them, and cocreate the program, noted Schuyler Jones, MD, associate professor of medicine at Duke University.

How did the approach to ADAPTABLE for studying aspirin use in patients with cardiovascular disease come about? As this was a pragmatic trial, what key adjustments did you have to make, and why?

It’s been a question that's been ongoing for probably decades. In fact, I remember Rob Califf [Robert M. Califf, MD, professor of medicine in the Division of Cardiology at Duke, and a former FDA Commissioner] mentioning that he wanted to study this when I was a young physician-clinician at Duke as an intern and resident. So it's definitely something that's been talked about for a long time.

The pragmatic nature and the opportunity presented itself when PCORI [Patient-Centered Outcomes Research Institute] funded PCORnet [The National Patient-Centered Clinical Research Network]. We needed a clinical question that was important to clinicians, important to patients, and then able to be potentially answered with newer methods, like direct-to-participant outreach and an open-label design. So that's how it came about.


The second question, I think, was about did we have to make any changes? Certainly we did make a few changes during the course of this study, but overall we held true to wanting to randomize patients 1:1 to the 2 most common doses of aspirin, 81 and 325 [mg]. We were able to finish the study, complete it in a short period, and provide an answer.

What are the most important takeaways from this study?

The story is really 2-fold. One is about aspirin, and then the other is about the process of the study, how we did it. And so for aspirin, it really is that there aren't differences in the effectiveness or safety of the 2 most common used doses. So we think that in most cases, because most patients right now are taking 81 mg, they shouldn't switch; they should stay on 81 mg.

From a process standpoint of the trial, we think that the way that we did this trial may be a way to do studies like this in the future. So, directly involve patients at every aspect, partner with them, cocreate the program, and stay true to why we're doing studies for our patients, as well as some of the novel methods like direct-to-participant enrollment and recruitment and using some of the data sources, like electronic health record [EHR] data and health insurance claims data.

 editorial wondered if a pilot study might have revealed the tendency for switching. Did the study group consider this option?

We really didn't. When you go directly to participants, like we did, it's hard enough to talk to patients about research. We really wanted it to be a streamlined, as-straightforward-as-possible clinical study. So if we did a pilot study, that would have required patients to do something different for some period of time, followed by the actual study. So I think that while the intent of the editorial was good, it's hard to think of how that would fit into how ADAPTABLE was run.

To be quite honest, pragmatism doesn’t have to be perfect. We just have to do it better and faster and more focused on the things that are important to people like clinicians and patients.

What lessons about the use of real-world evidence do you think ADAPTABLE gives the research community, especially in cardiology?

Cardiologists are so dedicated to data. And I think one of the criticisms that I always hear is, clinical trials are never done in real-world data. I don't think that's true. Clinical studies sometimes are a little bit more refined than what you would see in a generalizable, kind of everyday practice. But at least for this, it was an opportunity to truly get a large-scale study done in a generalizable manner. I think we showed that, with almost 500,000 patients approached and in the ability to use stuff that's already collected, like EHR data, like insurance claims data. That really, I think, is a model for the future.

Dr Schuyler Jones: ADAPTABLE Is a Study Model for the Future

Patients with an inherited, debilitating heart condition reported major improvements in quality of life while taking mavacamten, an investigational therapy now being evaluated by FDA, according to results presented today during the 70th American College of Cardiology Scientific Session.

Results were simultaneously reported in the 

If approved, mavacamten would be the first treatment to deal directly with the mechanism behind obstructive hypertrophic cardiomyopathy (HCM), which causes the heart muscle to contract far more than normal and thicken, causing dangerous symptoms and sometimes sudden death. For decades, clinicians have only been able to treat patients’ symptoms—using drugs developed to treat other heart problems—with limited effectiveness. Patients with obstructive HCM live with physical limitations and fatigue, and many undergo surgery to relieve the heart muscle thickening as their disease progresses.

Mavacamten, a targeted inhibitor of cardiac myosin, works to reduce the hypercontractility, which is often caused by genetic variants that put the heart into overdrive. By acting on the mechanism of HCM, this novel treatment not only slows the progression of the disease but also helps some patients improve.

 from EXPLORER-HCM, presented in August 2020 during the European Society of Cardiology virtual meeting, met all primary and secondary end points and showed significant improvements in multiple measures of patients’ symptoms and cardiac function. double-blind, placebo-controlled trial, patients with symptomatic obstructive HCM (LVOT gradient ≥50 mmHg and NYHA Class II-III) were randomized 1:1 to receive mavacamten (n=123) or placebo (n=128) for 30 weeks, followed by an 8-week washout period.

Today, investigator John Spertus, MD, MPH, of the University of Missouri-Kansas City and Saint Luke’s MidAmerica Heart Institute, presented results from the Kansas City Cardiomyopathy Questionnaire (KCCQ). The KCCQ is a well-known, frequently used study tool that grades rates patients’ quality of life responses on a scale of 0 to 100, with higher scores indicating better quality of life. When scores improve by less than 5 points, a patient’s condition is considered unchanged; a gain between 5 and 10 points is considered a small improvement; 10 to 20 points is considered a moderate improvement, and a 20-point gain is considered a large improvement. The KCCQ was administered at baseline and at weeks 6, 12, 18, 30 and 38. 

Results for the EXPLORER-HCM patients showed:

The average score for patients taking mavacamten rose quickly and was 9.1 points higher than the placebo group by the end of the 30-week treatment period.

Scales that focused on symptoms and physical limits showed that patients who took mavacamten did not maintain progress after treatment ended.

Among 19 clinical trials that have reported mean KCCQ differences between a study drug or intervention and placebo, results for EXPLORER-HCM rank in the top third. Spertus said of mavacamten, "It's really only eclipsed by the structural heart interventions."

36% of patients taking mavacamten reported improvements at least 20 points higher, compared with 15% taking placebo. By contrast, 9% of those taking mavacamten reported a declining score, compared with 23% taking placebo.

A key limitation that investigators reported in their findings: 28% of patients were missing data at baseline or in the follow-up. Spertus said during the session that this was largely due to administrative reasons, and researchers conducted "extensive analyses of the missing data" and there were no observable biases.

“This new analysis of the EXPLORER-HCM data provides important insights into the benefits myosin inhibition can have in improving the health status of patients with severe obstructive hypertrophic cardiomyopathy," Spertus said in a statement.

article, investigators wrote that one finding stands out: “In particular, the proportion of patients with very large (≥ 20 points) improvements in their KCCQ-[Overall Summary] score was much greater than that of patients randomly assigned to placebo, suggesting that for every 5 patients treated, 1 will feel substantially better."

The study authors contrasted the effects of mavacamten on patients with obstructive HCM with that of tafamidis, “the only other medical therapy approved in the past few years with such a large benefit in KCCQ scores,” for patients with amyloid heart disease. While tafamidis “sustained health status” in contrast with the decline seen in patients taking placebo, the authors observed that mavacamten brought about improvement in health, followed by “the unprecedented complete reversal of KCCQ improvements observed 8 weeks after treatment withdrawal.” The authors noted that this suggested treatment will have to be ongoing.

Spertus pointed out this phenomeon during his presentation. "What's particularly unique about this study design, and using a drug that appears to directly impact the underlying pathophysiology of the disease is we can see what happened after the drug was withdrawn." he said, pointing to the graph where the curve immediately fell below the line for the placebo arm as the effects of mavacamten dissipated. 

When treatment was withdrawn, "The health status of the mavacamten-treated patients returned right to baseline and was no different than the placebo treated patients."

After the EXPLORER-HCM results were announced last year, 

 was acquired by Bristol Myers Squibb (BMS) for $13.1 billion, and in March 2021 

 the BMS application, setting a goal date for approval of January 28, 2022, under the Prescription Drug User Fee Act (PDUFA).

1. Spertus JA. Fine JT, Elliott P, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. 

. Published online May 15, 2021. doi:10.1016/ S0140-6736(21)00763-7

The investigational drug for obstructive hypertrophic cardiomyopathy is in front of FDA, with an approval target date of January 28, 2022.

Patients Taking Mavacamten Report Big Leaps in Quality of Life

 since 2019 and has a BA in philosophy and journalism & professional writing from The College of New Jersey. 

-acetylglucosamine (GlcNAc) and N-glycan branching are associated with 

 (MS) in general and progressive MS (PMS), according to results of a cross-sectional study published in 

Previous studies have suggested N-glycosylation may hold relevance in MS and that the 2 may be related due to environmental factors or genetic sequence variants. In the first study of its kind, researchers investigated endogenous serum GlcNAc levels in humans with MS.

-glycan branching modulates cell surface receptor availability, and its deficiency in mice promotes inflammatory demyelination, reduced myelination, and neurodegeneration,” the authors wrote. “In humans, severe central nervous system hypomyelination results from loss-of-function variants in 

In the current analysis investigators “used a unique targeted liquid chromatography–tandem mass spectroscopy approach with ion pairing to assess serum levels of GlcNAc plus its stereoisomers (

-acetylhexosamine [HexNAc]) in healthy controls and patients with MS.” They also assessed whether serum levels of HexNAc are related to progressive disease course, severity, and disease-related neurodegeneration.

Between April 2010 and June 2013, 54 patients with MS and 66 healthy controls were recruited from centers in California to make up the discovery cohort. Any individual presenting with type 1 or 2 diabetes or kidney disease was excluded from the study.

The confirmatory cohort consisted of 180 patients with MS presenting to a neuroimmunology clinical trial unit in Germany between April 2007 and February 2016. Any patient who suffered acute relapse and/or used corticosteroids within 6 months prior to recruitment was excluded.

All participants underwent clinical examinations,  MRI, and optical coherence tomography (

) to measure retinal nerve fiber layer thickness (

), and provided serum samples that were reviewed by an analyst blinded to sample origin (patient or control).

Of those in the discovery cohort, 38 were women and the mean (SD) patient age was 42 (20) years. Thirty-three patients had relapsing-remitting MS (RRMS) and 21 presented with PMS. In the confirmatory cohort, 125 patients had RRMS, and 82 were women, while the mean patient age was 40 (9) years. Fifty-five patients had PMS in this cohort.

In the discovery cohort, the mean serum level of GlcNAc plus stereoisomers (HexNAc) was 710 (174) nM in healthy controls and marginally reduced in patients with RRMS (mean [SD] level, 682 [173] nM; 

In this same cohort, patients with PMS displayed significantly reduced levels compared with healthy controls (mean [SD] level, 548 [101] nM; 

The difference between patients with RRMS (mean [SD] level, 709 [193] nM) and those with PMS (mean [SD] level, 405 [161] nM; 

 = 7.6 × 10−18) was confirmed in the confirmatory cohort

Lower HexNAc serum levels correlated with worse expanded disability status scale scores (ρ = –0.485; 

Low baseline serum HexNAc levels correlated with a greater percentage of brain volume loss at 18 months (

Overall, results show “GlcNAc plus its stereoisomers are markedly reduced in PMS in 2 independent cohorts and that serum HexNAc levels are correlated with clinical disability and neuroimaging markers of neurodegeneration,” the authors wrote.

There are currently few data on biomarkers allowing detection of PMS, while diagnoses rely heavily on clinical observation and potential imaging biomarker candidates. Molecular biomarkers for PMS are scarce. However, “identifying simple molecular biomarkers for PMS that may facilitate early diagnosis, assess treatment effectiveness, and/or promote clinical development of novel treatment approaches is an unmet clinical need,” the researchers explained.

More research ought to be carried out exploring HexNAc levels as a potential biomarker for patients at risk of disease progression and to clarify the impact of potential physiological factors like diet or physical activity. It is also unclear why those with PMS may present with HexNAc deficiency.

Because both cohorts were recruited from academic tertiary referral centers, data may not reflect a real-world distribution, marking a limitation to the study. Cohorts also lacked racial and ethnic diversity and the cross-sectional nature of the study precludes any conclusions regarding the predictive power of HexNAc for MS disease development from being drawn.

“Further studies are required to develop our understanding of the relevance of 

-glycan branching and GlcNAc in PMS and of the clinical research and/or clinical management of disease progression in MS,” the authors concluded.

Brandt AU, Sy M, Bellmann-Strobl J, et al. Association of a marker of N-acetylglucosamine with progressive multiple sclerosis and neurodegeneration. 

. Published online May 10, 2021. doi:10.1001/jamaneurol.2021.1116

Using data from 2 independent cohorts, researchers identified a potential molecular biomarker for progressive multiple sclerosis (MS). 

Study Identifies Potential Molecular Biomarker of Progressive MS

In patients with diffuse large B-cell lymphoma (DLBCL), diagnosis-to-treatment intervals (DTIs) and pretreatment circulating tumor DNA (ctNDA) levels correlate with tumor burden, but ctDNA more objectively measured disease burden, reported 

The findings mean ctDNA can be to quantify and mitigate selection bias in prospective DLBCL clinical trials. The study was published in 

The authors noted that a univariate logistic regression model showed ctDNA and International Prognostic Index (IPI) individually predicted for short DTI.

“ctDNA levels predicted short DTI better than the IPI and were independently prognostic of event-free [survival] and overall survival in multivariable models also including the IPI and DTI,” the authors wrote.

Patients with more advanced-stage DLBCL had shorter DTI compared with patients with limited-stage disease, and patients with higher IPI also had shorter DTI. Meanwhile, median ctDNA levels were significantly higher in patients with advanced-stage DLBCL compared with patients with lower median levels of ctDNA.

“Collectively, our data suggest that ctDNA more objectively measures disease burden than DTI and could therefore have immediate utility to quantify potential selection biases in prospective DLBCL clinical trials,” concluded the authors.

A phase 2b clinical trial will examine the combination of maveropepimut-S (DPX-Survivac) and pembrolizumab (Keytruda) plus low-dose cyclophosphamide in patients with recurrent/refractory DLBCL. The trial will be a 3-arm, randomized, parallel-group, Simon 2-stage study. One arm will evaluate DPX-Survivac and pembrolizumab with cyclophosphamide, one arm will evaluate DPX-Survivac and pembrolizumab without cyclophosphamide, and the third arm will examine DPX-Survivac as a monotherapy.

Patients eligible for enrollment will have received 2 or more prior lines of systemic therapy and they have to be ineligible for, or have failed, chimeric antigen receptor (CAR) T-cell therapy or autologous stem cell transplant.

Learn more about the treatment regimen and the phase 2b trial 

Finally, Amitkumar Mehta, MD, assistant professor in the Division of Hematology and Oncology at the University of Alabama at Birmingham (UAB), director of the UAB Lymphoma Working Group, and codirector of the Bone Marrow Transplant-Immune Effector Cell Therapies Program at the O’Neal Comprehensive Cancer Center, discussed the safety profile of lisocabtagene maraleucel (liso-cel) and its use in relapsed/refractor large B-cell lymphoma.

Liso-cel is a CAR T-cell therapy that has been approved to treat adult patients with relapsed/refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including DLBCL. Cytokine release syndrome (CRS) and immune effector cell therapy–associated neurotoxicity are specialized adverse effects of CAR T-cell therapies, but according to Mehta, the incidence of CRS is “much lower” than the other 2 CAR T-cell therapies approved in this setting: axicabtagene ciloleucel and tisagenlecleucel.

Cytopenia, neutropenia, anemia, and thrombocytopenia were commonly observed adverse effects, but overall, liso-cell was “well tolerated,” Mehta said.

Typically, these patients have inferior outcomes to subsequent lines of therapy, and the overall response rates are inferior, but CAR T-cell therapies have “moved the science forward.”

“With lisocabtagene maraleucel, the most important [observation] was that it was welltolerated and the toxicity rates were far lower [compared with other CAR T-cell products], and it had significantly higher, or at least comparable, response rates. Overall, this is a very important treatment and approval,” Mehta said.

New research is helping to move the field forward for diffuse large B-cell lymphoma (DLBCL).

Latest in Leukemia and Lymphoma: Advancing Treatment in DLBCL

After 1 month we started seeing differences in the appearance of macrophages in mice that were exposed to electronic cigarettes, independent of nicotine, said Farrah Kheradmand, MD, a professor of medicine-pulmonary at Baylor College of Medicine and a staff physician at the Houston Veterans Affairs (VA) medical center. Kheradmand's research was presented at this year's 

American Thoracic Society (ATS) 2021 virtual conference

Can you give an overview of your talk "The Mechanisms of Injury from Vaping?"

We were very interested in the potential dangers of vaping with nicotine as an alternative to cigarette smoking. We did a very simple 2-by-2 experiment, because most of my patients at the VA wanted to know if vaping is safe, a safe alternative. That's how it's been advertised.

We took mice and we exposed them to vaping with or without nicotine, and cigarette or air. We wanted to compare what happens to inflammatory mediators in cigarette smoke compared to when you take nicotine in the form of aerosolized vaping. What we found was that they are completely different, meaning the inflammatory mediators that come to the lungs of mice when they're exposed to conventional cigarettes, is completely different than when you expose mice to electronic cigarettes. 

Interestingly, when we exposed them for a chronic period of time, meaning that we didn't want to know what the immediate response was, we wanted to know what happens long-term, because most people are not just vaping for 1 or 2 days. They want to vape for a long period of time. Our experimental model was such that we could actually test that hypothesis. When we exposed mice to 4 months of cigarette smoke, we saw what we'd seen before. Mice get emphysema, they get inflammatory mediators, in particular, both innate and adaptive immune cells into the lungs.

What we found was that, while we didn't see emphysema in mice that were exposed to electronic cigarettes, the lung macrophages—these are innate immune cells in the lungs—looked markedly different than mice that were exposed to air or cigarette smoke. What is more interesting is that it didn't matter whether they were exposed to nicotine or not. This happened independent of nicotine. That's really how the story got started, that the change alteration of the innate immune cells in the lungs. That sets us on the path that we discovered.

Based on your research, what could happen to a person's lungs when they vape?

What we've found is that we exposed mice to electronic cigarettes and as early as maybe a month into it—and again, we've done a 4-month [exposure] which is almost like lifelong smoking in a human life, so 4 months of electronic cigarettes—as early as 1 month, we started seeing differences in the macrophages' appearance, again, independent of nicotine, in mice that were exposed to electronic cigarettes. When we identified the macrophages [they had] kind of a glistening look. When we stained them for oil, and within these vacuoles, we found that there are large amounts of oil that are deposited within the macrophages. That's why they appeared more translucent, they appeared that they had vacuoles in them.

Initially, we thought they were undergoing apoptosis, or cell death. But we looked at all the markers of it, and we didn't identify any such activity. But what we looked for and found is that there was an accumulation of lipids inside the cell body. When we cracked the cells open and did an unbiased approach to try to understand what these lipids are, what we found is that they're actually lipids that are normally found in surfactant. Surfactant is this lubricant that keeps the alveoli open, so that we can continue to keep our lungs open and breathe. What happens is these particular molecules called surfactant get recycled—a third of surfactant gets recycled every hour.

This is a very, very active process. Macrophages and alveolar type 2 cells, these are specialized cells inside the lung, they talk to each other, if you will. They actually coordinate recycling of surfactants such that we always have a fresh layer of surfactant in our lungs to keep the lungs open. Part of the macrophage function is to actually perform this recycling of surfactant. What we surmised is that the function of the alveolar macrophages is disrupted, such that in order for them to recycle the surfactant, they can't play a catch up. So they actually accumulate inside their cell body. That's why over time, it a cumulative thing. 

While at about a month, we see a few macrophages that have this glistening and fat deposited, as the time progresses, at 3 or 4 months of exposure, we find almost the majority of the cells that have that phenotype. Meaning the more you get exposure, the more this process gets delayed, and the more macrophages become dysfunctional.

Farrah Kheradmand, MD, gives an overview of her research on the mechanisms of vaping-associated lung injuries. 

Dr Farrah Kheradmand Explains the Mechanisms of Vaping Lung Injury

According to recent research presented at the recent European Academy of Dermatology and Venerology (EADV) 2021 Spring Symposium, modified intermittent fasting may benefit patients with psoriasis.

reported, the study aimed to determine if there is a link between gut health and psoriatic lesions, as well as learn of any benefits of modified intermittent fasting in managing psoriasis. Modified intermittent fasting was defined as eating normally for 5 days and restricting calorie intake for 2 nonconsecutive days.

A total of 24 patients were enrolled; 12 were told to modify their diet and the other 12 ate normally. The fasting group ate 500 kcal twice per week on 2 nonconsecutive days, but on all other days were free to eat like usual. After the trial started, 2 patients were excluded, 1 for antibiotic use and the other for loss of follow up.

The Psoriasis Area and Severity Index score and Body Surface Area score was similar between both arms at week 0. At week 6 and week 12, the fasting group reported significant skin improvement, including less scaling and skin thickening, and 30% of patients saw a decrease in itching.

According to another EADV presentation reported by 

an imbalance in gut microbiota bacteria could play a significant role in the progression of hidradenitis suppurativa (HS), an inflammatory skin disease.

Researchers examined fecal samples from 15 patients. The samples were analyzed for regions of bacterial 16S ribosomal ribonucleic acid gene to investigate differences in their gut microbiota.

The relative abundance of 3 genera of bacteria—unclassified Clostridiales, unclassified Firmicutes, and Fusicatenibacter—were significantly lower in patients with HS than the control group. Lower amounts of these bacteria are known to disrupt the regulatory balance within the gut and stimulate an inflammatory response.

It is already known that the gut-skin axis is linked to multiple inflammatory and autoimmune skin diseases, such as acne and psoriasis.

Lastly, patients with psoriasis appear more likely to contract COVID-19, according to recent research presented at the 

American Academy of Dermatology Virtual Meeting Experience 2021

. A presentation at the meeting examined the link between systemic treatments and COVID-19 infection risk in patients with psoriasis, compared with the general population.

, researchers used a pharmacy claims database to assess the risk of COVID-19 infection in patients treated with systemic therapies compared with those treated with topical therapies.

More than one-third of patients with psoriasis had COVID-19 compared with the general population. Tumor necrosis factor α inhibitor correlated with a 18% reduction in COVID-19 incidence compared with those using topicals and 17% versus controls. Methotrexate was linked with a 25% reduction in COVID-19 infection, and apremilast had a 31% reduction when compared with those using topicals.

Interleukin-17 inhibitors were linked with a 36% increase in COVID-19 incidence versus 51% in those taking oral therapies. For patients prescribed ustekinumab, there was a 37% increase versus controls.

Updates from 2 recent medical meetings about links between the gut, psoriasis, and other skin disease, as well as the risk of COVID-19.

Psoriasis Recap: Intermittent Fasting, Microbiome-Skin Links, and More

® since 2019 after receiving his Bachelor's degree at Rutgers University–New Brunswick in journalism and economics.

Progression to PD-Related Dementia Predicted by Polygenic Hazard Score

A polygenic hazard score for predicting progression of PD over time to dementia (PDD) was shown in a study published in 

 loci were indicated to have been associated with PDD previously, whereas the discovery of the other 3 loci had not been previously reported. 

 exhibited a 2.5-times stronger effect on cognitive prognosis than 

, with patients carrying the lead variant found to decline more rapidly over time compared with patients who were noncarriers (

Findings From AAN 2021 Identify Gaps in Access to Device-Aided Therapies for PD

Discussing findings of an abstract presented at the American Academy of Neurology’s (AAN) 73rd Annual Meeting held virtually April 17-22, 2021, lead author Hubert Fernandez, MD, director of the Center for Neurological Restoration at Cleveland Clinic, spoke in an interview with 

® on the health inequities present in availability of device-aided therapies (DATs) for patients with PD.

His abstract, “Identifying Gaps in Parkinson Disease Patients Eligible for Device-Aided Therapies,” assessed the eligibility for DATs among those with PD via a validated screening tool called MANAGE-PD.

Grouping patients based on their level of DAT eligibility according to oral therapy efficacy, 19% were inadequately controlled by oral therapy and therefore qualified for DAT, although only half were found to have had discussions with providers on future use of these therapies.

Fernandez spoke further during the interview on the immediacy of this therapeutic approach for patients with PD who are eligible and how accurate screening could prove critical for long-term care.

Patient Survey Finds Dyskinesia, OFF Time as Most Prevalent Symptoms in PD

Another study presented at the AAN 73rd Annual Meeting sought to explore the impact of 2 common symptoms in patients with PD, 

, on both patients and their families and caretakers.

Analyzing data from 775 surveys, which included 527 patients with PD (68%) and 248 care partners (32%), 78% of respondents reported no or moderate understanding of dyskinesia and OFF, according to 

®. Moreover, 398 (51%) reported experiencing dyskinesia, 591 (76%) reported experiencing OFF at least occasionally, and 368 (48%) experienced both symptoms.

In examining the prevalence of symptom burden, 86% reported daily issues related to dyskinesia and 90% reported daily OFF issues, with more than half of both patient groups reporting having to change plans or activities due to their symptoms (dyskinesia, 61%; OFF, 60%).

Notably, 32% of those affected by dyskinesia said their symptoms have made social interactions more difficult, whereas 27% of those experiencing OFF symptoms were reported to have feelings of isolation and loneliness.

An overview of the latest news in Parkinson disease reported across MJH Life Sciences™.

Latest News in Parkinson Disease: Predicting Dementia Onset, Prevalence of Dykinesia and OFF Time, and More

Aspirin is the most common drug used after people have a heart attack, stroke, or bypass surgery, but until now doctors have not had clear evidence whether it’s best to give patients a low dose—the 81-mg “baby aspirin”—or a regular 325-mg dose.

A head-to-head comparison found the lower dose works just fine, as there were no significant differences in cardiovascular or major bleeding events in the 15,076-patient, real-world trial presented today during the 70th American College of Cardiology Scientific Session.

There was, however, better adherence with the low dose, so starting with the baby aspirin may be the best choice for most patients, said Schuyler Jones, MD, assistant professor of medicine at the Duke Clinical Research Institute and lead author of the study, called ADAPTABLE. Results were simultaneously published in the 

While many praised the trial’s pragmatic design, it had one big downside: doctors could not stop patients from changing doses, and many did. As a result, a commentator in the 

 questioned how reliable the findings are and whether investigators should have run a pilot that would have revealed this problem.

But Jones hailed the arrival of a direct comparison. “There really hasn’t been a clear answer about what is the most effective and safe dose of aspirin for these patients. Instead, there have been conflicting findings, with some research suggesting 81 mg may reduce the risk of bleeding, but the higher dose may provide more effective prevention of heart attacks and stroke,” he said in a statement. “These earlier studies have primarily investigated aspirin—either 81- or 325-mg daily dose—compared with placebo.”

The study design combined classic clinical trial elements with electronic health records and claims data, including that of both commercial payers and CMS. Patients took part by mail, email, or phone and enrolled through a secure website that allowed follow-up every 3 to 6 months for a period of just over 2 years (26.2 months), from April 2016 to June 2019. Patients had to have established atherosclerotic cardiovascular disease plus 1 other risk factor; the median age was 67 years. Most patients were White, 9% were Black, 3% were Hispanic, and 1% were Asian. Patient groups were well balanced at the start of the study, with 7540 taking 81-mg and 7536 taking 325-mg daily doses.

However, of the 96% taking aspirin before the study, 85% were taking baby aspirin, and during the study, switching doses was far more common among those randomized to the 325-mg dose (41.6% in this group switched their dose at least once) compared with the 81-mg dose (only 7.1% switched).

“We made every effort to encourage them to stay on their study dose, but nevertheless people felt very strongly about it, so the differential effects of the 2 doses are less clear since dose switching occurred very frequently, especially in the 325-mg group,” Jones said, while noting that many patients in each group stayed on the assigned dose for over a year. Investigators will conduct additional analyses to learn reasons why patients switch doses.

If patients are taking a 325-mg dose of aspirin and tolerating it well, they are likely fine to continue—but those resuming aspirin or starting it for the first time should probably start with the low dose, he said.

Colin Baigent, of Oxford University, was less convinced. “Because switching was not likely to have been at random, bias arising from this degree of crossover could have obscured a true difference in efficacy or safety (or both), and moreover it is also not possible to conclude that the lack of any significant difference between the 2 dose groups implies equivalence of the effects of the doses,” he wrote in the 

The primary effectiveness outcome, a composite of all-cause death or hospitalization for heart attack or stroke, took place in 590 patients taking the 81-mg dose and 569 patients taking the 325-mg dose, for an HR of 1.02 (95% CI, 0.91 -1.14; 

The study’s major safety end point was hospitalization for bleeding that required transfusion. This was a rare occurrence, happening in only 53 participants taking the 81-mg dose (0.63%) and 44 taking the 325-mg dose (0.60%), for an HR of 1.18 (95% CI, 0.79-1.77).

Results were consistent regardless of age, race/ethnicity, gender, and prior use of dual antiplatelet therapy or whether patients had diabetes or chronic kidney disease.

During the study, 11% stopped taking aspirin in the 325-mg group compared with 7% in the 81-mg group.

ADAPTABLE is the first clinical trial to use PCORnet, the National Patient-Centered Clinical Research Network, a partnership of clinical research networks funded by the Patient-Centered Outcomes Research Institute, which funded the study.

While Jones said his team will do more work to tease out why so many patients switched doses, the big winner may be the study's methodology, which won praise from commenters, including Baigent.

Jane Linderbaum, APRN, CNP, FACC; a member of the ACC Annual Scientific Session Program Committee and cardiovascular nurse practitioner; who is an assistant professor of Medicine at the Mayo Clinic, in Rochester, Minnesota, commended Jones and the research team during a press conference on “this patient-centric study.” She predicted the real-world methodology would become more common.

“There's going to be lots of studies looking to learn from what you've done,” Linderbaum said, praising the use of electronic health records and the fact that patients could enroll themselves and manage their own consent process. “This is a great opportunity for a low-cost trial … during a very challenging time in medicine, both for clinicians, certainly, and for patients.”

1.  Jones WS, Mulder H, Wruck LM, et al, for the ADAPTABLE Team. Comparative effectiveness of aspiring dosing in cardiovascular disease. 

. Published May 15, 2021. doi:10.1056/NEJMoa2102137

2. Baigent C. Pragmatic trials—need for an ADAPTABLE design. 

Results presented at the American College of Cardiology's 70th Scientific Session show most patients prefer a smaller dose and are more likely to stick with it.








