00:55 Educating your patients with actinic keratosis on progression to squamous cell carcinoma and field cancerization.

06:15 The different treatments options available for actinic keratosis.

07:42 Evidence based treatment selection in actinic keratosis; sequencing and combining therapies

10:48 Photodynamictherapy for treatment of actinic keratosis

20:30 Comparison studies on photodynamic therapy used with various used in combination with formulations of photosensitizing agent

24:10 Optimizing the use of photodynamic therapy for extremities in patients with actinic keratosis

27:50 The efficacy, safety and adherence of the different treatment modalities based in actinic keratosis

In this episode of MEDcast, expert dermatologists discuss actinic keratosis, a premalignant skin condition. They are sharing their thoughts on the importance of early diagnosis and treatment and are delving into treatment options, in particular photodynamic treatments.

 Empowering Patients: Navigating the Progression Risks of Actinic Keratosis and Optimizing Treatment Selection

Anthony Rossi, MD

Iron deficiency is currently screened at a ferritin threshold of 15 ug/mL, well below an accepted 25 ug/mL threshold.

Daniel Wang: A More Appropriate Ferritin Threshold is Cost-Effective for Iron Deficiency Screening

Screening for iron deficiency (ID) at a ferritin threshold of under 25µg/L is a cost-effective and more accurate identification and treatment strategy for women with ID.

 66th American Society of Hematology (ASH) Annual Meeting and Exposition

, held December 7-10, 2024, in San Diego, California, by Daniel Wang, Yale School of Medicine.

“The current world health organization guidelines have the lower limit of normal for serum ferritin at 15 micrograms per liter, whereas we know from physiological studies… that a more appropriate threshold is probably 25-to-30, maybe even as high as 50 micrograms per liter, so a huge swath of women of reproductive age who are just going undiagnosed and untreated in a lot of cases,” Wang told 

Wang and colleagues found that screening for ID with a ferritin threshold under 25µg/L is the cost-effective strategy in 100% of 10,000 Monte Carlo iterations, accruing $212,000 in costs and generating 24.3 Quality-Adjusted Life Years (QALYs), compared with $211,000 and 23.3 QALYs with a screening threshold of 15 µg/L, or $210,000 and 22.3 QALYs with no screening. Overall, the data show that the incremental cost-effectiveness ratio of 25 µg/L compared to no screening is $940/QALY which is accepted under willingness-to-pay thresholds in the United State.

The investigators also found that treatment with iron dextran (ICER = $1,700/QALY) is also cost-effective in patients with ID. These findings were supported with sensitivity analyses.

“…Cost should not be a barrier for the screening and treatment of these women and at a population level. If we can raise the bar, I really think so, so many people would benefit,” Wang said.

Wang D, Glaeser-Khan S, Wang DY, et al. Sex, Lies, and Iron Deficiency in 2024: Cost-Effectiveness of Screening Ferritin Thresholds for the Treatment of Iron Deficiency in Women of Reproductive Age. Presented at: ASH Annual meeting; December 7-10; San Diego, California. Abstract 277

Daniel Wang

 What’s really important—and we’re not here to give advice to the manufacturer of inclisiran—is the reputation a drug develops when it’s brought to the marketplace. It sticks. To Dean’s point, if you look at data published by Seth Baum and others, they found that the utilization of PCSK9 was somewhere about 0.3% of those who were eligible.

What happened was you had the insurance payers creating these incredible speed bumps. It didn’t really matter. The manufacturers of PCSK9 inhibitors cut their price in half. As Dean, Manesh, and Linda have said, the access to the PCSK9 inhibitors has certainly become easier. But the doctors just aren’t interested in prescribing. As far as they’re concerned, it’s a drug that’s very difficult for patients to access. It’s an “expensive” drug. I urge the manufacturer of inclisiran to think the process through, so that when this drug finally comes to market, it is accessible. 

Otherwise, you’re going to have the same issues that we face with PCSK9 inhibitors. Perhaps we need to inject some artificial intelligence into value-based care instead of what seems to be artificial insanity. We need to be able to count on really good algorithms to determine appropriate use for these compounds.

I still have heterozygotes being turned down for PCSK9 inhibitors. It’s insanity out there. What we really need is really good artificial intelligence, not artificial insanity, in terms of making sure these drugs are being used in the appropriate patient at the appropriate time.

 Norman, that was a wonderful take-home message. In fact, I’m going to start with Dean, Manesh, and Linda; you’ll be last. Give me a similar take-home message, something you think our audience needs to hear from you. Dean?

 In secondary prevention, the LDL [low-density lipoprotein] goal is less than 70 mg/dL and probably lower for all our patients. That’s going to require combination therapy, the best statin dose you can get them on, and then other drugs.

If the cost of the medicine is too expensive, then use ezetimibe. For primary prevention, family history, pay attention to risk-enhancing factors in the guidelines and calcium scoring. That’s how we can get these patients treated earlier, so we’re not in the situation where they’ve already had events and you’ve got to be that much more intensive with regard to their treatment.

 We’re at the age where we have an explosion of possible therapies for our patients, which is great. The take-home message for me is this isn’t about cardiology or specialty care; it’s about primary care. This is about getting the message and the care pattern and the access to the primary care. That’s how we’re going to affect the population health, by getting these therapies—statin, inclisiran if it comes on the market, PCSK9 as we’ve just heard—into the hands of our primary care doctors and getting them comfortable with having the conversation with patients to get the therapies to them.

 That’s a great comment. Linda, you have the last take-home.

I just want to reemphasize lifestyle. Diet is absolutely critical. You can have somebody who is not at goal and they’re eating a terrible diet, and they can have really good results from changing that diet. Using our licensed nutrition folks and getting these people to improve their diet is very much a part of the picture.

 Thank you very much. I’m Dr Keith Ferdinand for HCPLive®. We’ve had a rich and informative discussion. Linda, Dean, Norm, and Manesh have given us a wealth of ideas and information, reviewed data, and given some opinions on where we are now with the intent of lowering risk in patients who are high risk, including the FH [familial hypercholesterolemia] patients, patients with ASCVD [atherosclerotic cardiovascular disease].

If you enjoyed watching this HCPLive® Peer Exchange, if you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your in-box. Thank you very much for listening to this program.

Final thoughts from expert KOLs regarding treatment decisions and how they relate to patient accessibility when manage dyslipidemia. 

Treatment Decisions and its Relation to Patient Accessibility  

Dean Karalis, MD

One of the things I think we should revisit in this discussion is the staging of diabetes. 10 or 20 years ago, there wasn't really staging at all. Either you didn't have type 1 or you did have type 1 diabetes. We asked Dr Sims to revisit that when she discussed it too. Type 1 staging is where you're antibody positive, but there are no symptoms, but there's also no change in blood sugar fluctuation. If you give someone a glucose tolerance test, they produce plenty of insulin still, but the antibodies are doing their magic and working against those beta cells. And then we have stage 2 where the antibodies are positive and yet during a glucose tolerance test that those blood sugars start to rise. And that was that first phase insulin response that she was discussing. That's the hardest time that you need the most insulin is when you eat carbohydrates. If you think about that as a clinician, that makes the most sense is that that would fail first and not the fasting blood sugar. When you think about fasting, the patient has had all night to make enough insulin to get that blood sugar down when you check it.

Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES: 

Can you tell us, I know when someone has 2 or more auto antibodies, what's the chance that they're going to develop type 1 diabetes?

Almost 100% in their lifetimes. And in the beginning, we thought about diabetes as something that came on as a child. It was juvenile onset for so many years. We have lots of patients who get it as a child, but we also have lots of people who get it as an adult. And you and I both have had patients in their 60s, 70s, 80s develop type 1 diabetes. How do we know how long they were antibody positive? We don't. But you have a 100% chance or close to it if you have two or more antibodies positive.

Yes. The staging system is interesting. There's not a ton of awareness about it. It's in the ADA standards of care, but I don't think a lot of people are aware of it. And especially in adults where type 1 diabetes tends to be more slow progressing, The staging is very helpful. For example, a common, I guess it's not so common, but I've experienced it in a number of my patients where a woman is diagnosed with gestational diabetes, right? And then come to find out, she actually has the auto antibodies. And I've seen several cases where the endocrinologist, someone thought hey, let's, you didn't seem like a person, you didn't have the characteristics that might put you at higher risk of developing gestational diabetes. Let's go ahead and check those auto antibodies. And sure enough, they've had them. But the neat thing about it is we've been able to catch it so early that in terms of the treatment, often we don't have to go straight to needing basal bolus insulin or using an insulin pump. When you catch it early, especially in adults where it's slower progressing, we can start off sometimes with even other therapies like with using metformin, but often maybe just with a long-acting insulin and not requiring mealtime insulin. It's interesting. There's a lot of benefits to this staging and to early detection.

Yes, and think about, when you think about diabetes, type 1 diabetes and the burden that comes with the management, the day-to-day management, every time you look at food, every time you think about how far is the gate that I walk to at the airport? Is that going to drop my blood sugar? What's going to happen next? There is a real burden that comes with this disease. Knowing ahead of time and using therapies as quickly as possible and addressing them as opposed to waiting will be a real option for patients.

I'm curious your thoughts on this. Of course there is a burden, but now we do have so many better tools, so many better technologies. We've got all these automated insulin delivery systems. I mean, I've got several patients that are easily able to get that 70-80% time in range. What do you think with all the new technologies, is it still as much of a burden? Do we still, should prevention or should cure? Is it still important?

I think it is. And some of the reasons are that we don't know. It's very hard sometimes. We can all talk about the patient, the person with diabetes who's had an A1C of 12 and they end up with eye disease, right? And those people that suffer and that they're trying to just get food on the table and trying to get their heat turned on a regular basis, their blood sugar sometimes can reflect those challenges in their lives. The social determinants of health when you, with type one diabetes are very similar to the social determinants of health with type 2 diabetes and the management of it all and the overwhelming feeling. So AID, automated insulin delivery, is still not for everyone. And I certainly, I have amazing patients who do very, very well. But I also have a lot of patients who really struggle, even with amazing technology that wasn't here 20 years ago, to get to goal and not feel like that's all they do every day. There is a place for delaying the onset. You could choose not to use the medication. We always want to provide a fair and balanced discussion. And this is a harder one because if you don't use the drug, there isn't another drug option. But you could just wait for the diabetes to come. And I don't know that we can always pick the patient that will suffer or have higher burden from the disease than other people. Because you and I both have those, we have both patients who seem to suffer a lot and who just struggle with the management, the daily management, and others who don't have that same challenge with it. They don't like it. They never wake up and say, there's a great diabetes day. But they also don't have the depression and some of the other things that kind of come with that wear and tear of diabetes daily.

Yes, I'm with you. I mean, I'm thrilled with all the different tools and the technologies we have. And I do tell my patients, I'm like, this is, if you must develop diabetes, this is the best time in history to have it because we have all these tools. But the reality is for automated insulin delivery currently, it does require wearing 2 sites. Your pump, you have your CGM, maybe at some point it'll be consolidated into one, but it's still wearing something all the time. And when you wear something, it's you have something on your body. If it falls off, that's a problem, right? You're not getting what you need. I agree with you. I think the cure, the prevention should still be a major focus. And I'm very excited to see that we are finally moving the needle on this. I mean, how many times have you heard a cure is five years away?

50 years now. Right? We've been hearing it for our whole careers. Right.

Right, and I don't know if the cure is 5 years away, but I know that we have gotten a lot closer. The fact that we can delay diabetes by a few years. And even the thing is, it's not just the delay. Because it's also the preservation of those beta cells. Even if you say, ok, well, the person got 2 or 3 extra years of not having type 1 diabetes, well, when they did get it, what were those first few years like? Maybe they were a lot easier. Maybe they were able to be managed on initially a long, or just a little bit, a tiny bit of insulin. They weren't having these wide fluctuations in glucose levels. If we've improved their quality of life for several years, that is something.

: I agree with you wholeheartedly. I also loved her discussion around adding other drugs. This is not going to be the 1 and only drug that is ever going to be used to delay the onset of all kinds of autoimmune diseases. They're looking at Crohn disease, they're looking at, other groups are looking, other companies are looking, right? And that's important too. Is there going to be where we say, you have these 3 antibodies, but you don't have this one. Can we make that person a cocktail in the future to delay the onset longer, to prevent, what if you could get to 10 years? Would you do that? Those are the discussions in the future that we can have.

Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES

: Yes, it's definitely very exciting. Well, thank you for this very rich and informative discussion, and thanks to our audience for tuning in. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming MedCast® episodes and other great content in your inbox.

Drs Diana Isaacs and Natalie Bellini discuss the everyday challenges of managing type 1 diabetes and underscore the need for new treatments to improve the quality of life for people living with type 1 diabetes

Challenges in Managing Type 1 Diabetes and Pressing Need for New Therapies

Emily Sims, MD

Experts comment on emerging treatments for anhedonia and highlight lifestyle modifications that support patients with Major Depressive Disorder.

Emerging Treatments of Anhedonia in Patients with Major Depressive Disorder

In addition to the dextromethorphan-bupropion combination, the clinicians review other evidence-based treatments for anhedonia. These include medications modulating dopamine, glutamate, kappa opioid receptors, and psychedelics. Lifestyle approaches like exercise, diet, sleep, social connection, and purpose are also critical, improving motivation and pleasure by enhancing BDNF, endorphins, and dopamine while decreasing inflammation.

They emphasize assessing and tracking residual symptoms like anhedonia even in patients considered asymptomatic or “in remission” on rating scales, as lingering lack of enjoyment, drive, or interest predicts later recurrence and dysfunction. Using practical measures of life engagement and specific hobbies, relationships, or tasks is recommended over formal rating scales to identify ongoing areas of impairment.

In closing, the clinicians express excitement about the expanding treatment options to address unmet needs like motivation and pleasure that have been resistant to standard interventions. They urge clinicians to utilize both new tools emerging from ongoing research as well as digital measures and benchmarking to ensure treatment gets patients to optimal functioning, not just minimal symptom reduction. Keeping skills updated and identifying patients struggling with residual symptoms is key to enabling fuller recovery.

This summary was AI-generated and edited for clarity. 

Dr Andrew Cutler and Dr Greg Mattingly comment about emerging treatments to treat anhedonia and highlight lifestyle modifications that support the wellbeing of patients with Major Depressive Disorder.

Gregory Mattingly, MD

Fast, accurate diagnosis of multiple sclerosis (MS) can be life-changing for patients, and new updates to the existing criteria are aiming to make that possible, ensuring that those living with the condition get the treatment they need when it matters most. Building on decades of research and clinical experience, the McDonald diagnostic criteria have served as a cornerstone in diagnosing MS, evolving over the years to keep up with the advancements occurring in the field. First established in 2001

, the criteria aim to balance sensitivity and specificity in identifying MS.

Since 2021, a panel of experts has been refining the guidelines to integrate cutting-edge insights into the disease’s biological mechanisms. This latest update prioritizes earlier and more accurate diagnoses by incorporating advanced imaging and biomarker tools alongside clinical evaluations, enabling timely treatment and improved outcomes for patients. Earlier this year, at the 

2024 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 18-20 in Copenhagen, Denmark

, unveiled these newly updated criteria during a scientific session cochaired by 

Overall, these revisions included the adoption of advanced diagnostic methods and the development of age-specific criteria to more accurately diagnose MS in both younger and older populations. The aim of these changes is to enhance diagnostic precision by examining biomarkers of MS-related damage that go beyond observable symptoms. The finalized guidelines are expected to be published in a peer-reviewed journal by early 2025, although delays in the review process are possible. Once released, organizations like the 

 and ECTRIMS plan to educate providers and patients, ensuring that clinicians effectively implement the updates into their practice.

Voices of clinicians featured in recent conversations with 

 offer a collective and valuable perspective on how the updated McDonald criteria will influence MS diagnosis in clinical practice. Each of the insights from the experts bridge the gap between the progress made in cutting-edge research and the experiences of day-to-day patient care. As part of 

 series, these clinical views expand the conversation surrounding the new criteria beyond the guidelines themselves, highlighting their practical implications for improving outcomes in MS management overall.

Proposed New Guidelines for Diagnosing MS

"During my presentation, I realized that while they may look quite complex, they are not so. Again, I want to highlight that the criteria are very much evidence based. I think this is the first time the entire set of criteria is truly evidence-based—they are sensible, logical, and the diagnostic algorithm is very easy to follow,” Montalban, chair of neurology at Hospital Universitari Vall d’Hebron, told 

 in a recent interview. As highlighted by Montalban, the proposed new revisions to the MS diagnostic criteria aim to improve accuracy and consistency in diagnosis.

Key changes in the new criteria presented at ECTRIMS 2024 included recognizing radiologically isolated syndrome (RIS) as MS in specific cases, adding the optic nerve as a fifth anatomical location, and removing the requirement for dissemination in time (DIT). Updates to dissemination in space criteria were introduced alongside the inclusion of kappa free light chains as a diagnostic tool. Montalban also highlighted in the presentation that the same criteria can be applied to both primary progressive MS and relapsing-remitting MS, with stricter standards for diagnosing older patients or those with comorbidities like migraine or vascular disorders.

“I view this as a significant shift in how we diagnose MS, primarily because we no longer require a clinical syndrome, such as a relapse or progression. So, we’ll be diagnosing MS in patients with atypical symptoms or even no symptoms,” said 

, consultant neurologist at Queen's Square MS Center in London, told 

. “It's going to be an interesting time ahead.”

Additional key changes featured in the presented criteria included the recommendation of optional tools, such as the central vein sign (CVS) and paramagnetic rim lesions (PRLs), for specific cases, and myelin oligodendrocyte glycoprotein antibody tests suggested for diagnosing children and adolescents. During the presentation, Montalban emphasized using paraclinical evidence for the confirmation of MS diagnoses across different patient populations. According to the clinicians 

 spoke with, these revisions may reflect a more nuanced approach to MS diagnosis, accommodating a broader range of clinical presentations.

Calabresi, codirector of the Precision Medicine MS Center at Johns Hopkins University, shared with 

that incorporating the optic nerve as a "fifth topology" or classic location represents a significant change in the diagnostic criteria for MS. While optic neuropathy or optic neuritis has long been recognized as a common MS manifestation, it was not previously included in the criteria.

"I think adding that will be useful," he said. He also highlighted the integration of newer imaging technologies, such as optical coherence tomography (OCT), which can now assess inter-eye differences. Specifically, an inter-eye difference of more than 6 microns in the retinal nerve fiber layer or 4 microns in the ganglion cell inner plexiform complex could help confirm a diagnosis of optic neuropathy.

Joseph Kuchling, MD, a postdoctoral research assistant at Charité University Berlin, also highlighted an important update to the diagnostic criteria: the inclusion of specific markers like the CVS and PRLs. "These additions could help improve the specificity of diagnoses," Kuchling told 

, noting that although the 2017 McDonald criteria were highly sensitive, they lacked specificity in real-world practice.

With the new criteria, there is hope for greater confidence in diagnosing MS and initiating treatment earlier in patients presenting with strong indicators such as CVS, without needing to consider other differential diagnoses like sarcoidosis or neuromyelitis optica spectrum disorder. However, Kuchling emphasized the importance of observing how the new criteria perform in clinical practice.

Marcello Moccia, MD, PhD, assistant professor at the University of Naples, explained to 

that a major advancement in the updated criteria is the transition from viewing MS as a purely clinical diagnosis to recognizing it as a biological disease. "This shift is evident in two key aspects of the criteria," he said. The first involves RIS, which was previously described as a set of MRI findings but can now be diagnosed as MS in specific cases where biological evidence of the disease is present. Additionally, the criteria for relapsing and progressive forms of MS have been unified.

"In the past, we used two separate criteria for different clinical presentations, but biologically, the disease is the same," Moccia explained. He added that although this change may have a minimal impact on clinical practice, it significantly advances the understanding and interpretation of MS.

As the revised MS diagnostic criteria continue to evolve, several open questions remain for clinicians to take into future consideration. According to Montalban’s presentation, one area that may require further investigation could be the demonstration of DIT using advanced techniques such as visual evoked potentials (VEP) and OCT, which could offer more precise diagnostic insights. Additionally, the refinement of using PRLs and CVS as diagnostic tools in specific contexts may need further exploration according to Montalban and colleagues.

The criteria’s application to cases of solitary sclerosis and other atypical MS presentations also could warrant further study to ensure broader applicability. Another key question presented at ECTRIMS 2024 on future revision is how the criteria perform across diverse populations, particularly in regions like Asia and Latin America, where MS presentations and risk factors may differ. Finally, Montalban highlighted the integration of other emerging biomarkers for MS diagnosis, beyond the currently accepted standards, that could be an essential consideration in the future revisions.

"A lot of the discussion hinged on what we should do for the next round of criteria. Another point is that we change the criteria every few years, right? That's the model we've been using. But is there a different model that might work better, where we adjust the criteria more frequently as data is produced? We heard some of that,” said 

, associate professor of neurology at the Cleveland Clinic Lerner College of Medicine, told 

. “So, definitely, I think just because we have a new set of diagnostic criteria doesn't mean we've solved all the problems. We need to continue working on things and evolving how we make a diagnosis of MS."

The development of the revised McDonald diagnostic criteria represents a significant milestone in the field of MS for both clinicians and patients receiving care, supported by a forthcoming publication of a paper and diagnostic algorithm. As highlighted in the ECTRIMS 2024 presentation by experts, these updates are the result of extensive consultation with the wider MS community and are designed to address both current challenges and emerging insights.

Based on Montalban’s presentation, clinicians can expect additional papers planned to expand on specific aspects such as imaging advancements, visual system assessments, and the role of biomarkers. Overall, experts recognize that the implementation of these changes globally will possibly require careful consideration of resources, education for providers, and patient accessibility. Thus, a global education campaign may be essential to ensure that MS clinicians worldwide can adopt these criteria effectively into their practice, improving diagnostic accuracy and patient outcomes as well as addressing the unique challenges and perspectives of patients living with MS.

“In essence, the disease hasn’t changed but every few years, new criteria are introduced. The question is, what are these criteria really for? I think they serve several purposes. One is for non-specialists who need help in defining what the disease might be. I believe some of the additions to the new criteria—partly based on new technologies—have genuinely improved the criteria,” said 

, the William S. and Lois Stiles Edgerly Professor of Neurology at Yale School of Medicine, 

. “But ultimately, I should point out that the diagnosis of MS is a pathological diagnosis, and what we do clinically is add various measurements that increase the probability of making an accurate diagnosis.”

McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121-127. doi:10.1002/ana.1032

Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173. doi:10.1016/S1474-4422(17)30470-2

Montalban X. 2024 Revisions of the McDonald Criteria. Presented at ECTRIMS Congress; September 18-20, 2024; Copenhagen, Denmark. Scientific Session 1: New diagnostic criteria.

European Committee for Treatment and Research in MS. McDonald Diagnostic Criteria. Accessed November 12, 2024. https://ectrims.eu/mcdonald-diagnostic-criteria#

Recent updates to the McDonald diagnostic criteria for multiple sclerosis (MS) aim to enhance diagnostic accuracy and timeliness, incorporating advanced imaging and biomarkers. These revisions, presented at the 2024 ECTRIMS Congress, include recognizing radiologically isolated syndrome as MS in specific cases, adding the optic nerve as a diagnostic location, and removing the requirement for dissemination in time. The criteria now apply uniformly to both primary progressive and relapsing-remitting MS. Future revisions may explore further integration of emerging biomarkers and diagnostic tools.

With new revisions of the MS diagnostic criteria being made, clinicians highlighted key updates and the broader implications it has for diagnosis, treatment, and healthcare practices worldwide.

Advancing the Diagnostic Criteria for Multiple Sclerosis: A New Era of Early Detection and Precision 

Isabella Ciccone, MPH

Treatment Nonresponders in Atopic Dermatitis

Video content above is prompted by the following:

How do you define treatment nonresponders in AD?

Panelists discuss how they define treatment non-responders in atopic dermatitis (AD), focusing on factors such as lack of significant improvement in symptoms, inadequate response to therapy, or failure to achieve treatment goals despite proper adherence and adjustments.

Jennifer Soung, MD

This article was originally published in 

The US Food and Drug Administration (FDA) has approved Abrysvo, a 

The approval will allow Pfizer to move forward with the vaccine for individuals aged 60 years and older to prevent lower respiratory tract disease caused by RSV.

) vaccine, is composed of 2 preF proteins specifically chosen to optimize protection against RSV A and B strains.

“A vaccine to help prevent RSV had been an elusive public health goal for more than half a century," said Annaliesa Anderson, PhD, senior vice president and chief scientific officer of vaccine research and development at Pfizer, in a statement. “Abrysvo will address a need to help protect older adults against the potentially serious consequences of RSV disease. We are extremely grateful to the clinical trial participants, study investigator teams and our dedicated Pfizer colleagues for their roles in making this vaccine available.”

In the more than 50 years of working to develop an RSV vaccine, Abrysvo is the world’s second-ever to be granted approval. Last month, 

GSK’s Arexvy (RSVPreF3 +AS01E) was approved

 to prevent lower respiratory tract disease (LRTD) caused by RSV in adults 60 years and older.

The FDA's decision to approve Abrysvo as well was based on data obtained from the pivotal Phase 3 clinical trial (NCT05035212) known as RENOIR (RSV vaccine Efficacy study iNOlder adults Immunized against RSV disease). RENOIR is a global, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, immunogenicity, and safety of a single dose of the vaccine in adults aged 60 and older.

Approximately 37,000 participants were enrolled in RENOIR, with half receiving RSVpreF 120 μg and the other half receiving placebo in a 1:1 ratio. RENOIR is an ongoing study, with efficacy data being collected during the second RSV season.

Edward E. Walsh, MD, Professor of Medicine at the University of Rochester Medical Center and principal investigator of the RENOIR trial, commented, "This 

 demonstrated the serious consequences and potential health risks this virus poses for older adults. Today’s FDA approval of Abrysvo recognizes significant scientific progress, and importantly helps provide older adults potential protection against RSV and an opportunity to improve community health by helping prevent the disease.”

RSV is a contagious virus that commonly causes respiratory illnesses worldwide. It primarily affects the lungs and breathing passages, often leading to severe illness or even death. In the US, RSV poses a considerable burden on older adults, with disease severity increasing with age and comorbidities such as chronic obstructive pulmonary disease, asthma, and congestive heart failure.

In most healthy individuals, RSV manifests with mild, cold-like symptoms. Most people recover within 2 weeks, often without knowing they had contracted RSV. Infants and young children, however, are also susceptible to the worst of RSV infection. Thus, Pfizer is also seeking approval to administer 

 to pregnant persons, with the goal of preventing medically attended lower respiratory tract disease (MA-LRTD) and severe MA-LRTD caused by RSV in infants from birth to 6 months of age.

 by the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), and a decision is expected by August 21, 2023.

Regarding the use of RSV vaccines in older adults, the US Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP) is scheduled to meet on June 21, 2023, to discuss recommendations. Pending the outcome of this meeting, Pfizer expects Abrysvo to be available in the third quarter of 2023, just ahead of the anticipated RSV season this fall.

In addition to this recent approval, Pfizer reported positive top-line results earlier this month from a Phase 3 study that evaluated the safety and immunogenicity of Abrysvo coadministered with seasonal inactivated influenza vaccine (SIIV) in adults aged 65 and older.

Furthermore, Pfizer announced its plans to conduct multiple clinical trials evaluating RSVpreF in healthy children aged 2-5 years, children aged 5-18 years with comorbidities, adults aged 18-60 years with comorbidities, and adults aged 18 years and older who are immunocompromised and at high risk for adverse RSV outcomes.

The approval for Abrysvo represents the second RSV vaccine approved for adults aged 60 years and older in the last month.

FDA Approves RSV Vaccine for Older Adults

Nina Cosdon

Ralph DeFronzo, MD is a Professor of Medicine and Chief, Diabetes Division at UT Health San Antonio.

Ralph A. DeFronzo, MD: Noxious Nine and Mifepristone for Hypercortisolism in T2D

22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC)

, Ralph DeFronzo, MD, a professor of medicine and chief of the diabetes division at UT Health San Antonio, discussed the evolution of his influential concept, the Ominous Octet, which outlines the multiple defects contributing to 

Initially introduced in 1987 as the "triumvirate," focusing on insulin resistance in the liver and muscle and beta-cell dysfunction, the model expanded in 2008 to include five additional key players: obesity, the gastrointestinal tract, excess glucagon secretion, the kidney, and the brain, all of which exacerbate insulin resistance and beta-cell failure.

DeFronzo then shifted focus to a novel discovery about hypercortisolism in patients with difficult-to-control T2D, a condition in which the adrenal glands secrete excess cortisol, aggravating many of the defects in the ominous octet. The CATALYST study revealed that approximately 24% of these patients have elevated cortisol levels, which significantly contribute to their poor glycemic control. Treatment with mifepristone (Korlym), a glucocorticoid receptor blocker, led to a surprising 1.5% reduction in HbA1c, compared with 0.15% for placebo (placebo-adjusted reduction, 1.32%; P <.0001). In addition, mifepristone achieved a notable decrease in medication requirements, showcasing a promising new therapeutic avenue for this previously under-recognized cause of diabetes.

DeFronzo emphasized the importance of educating clinicians about hypercortisolism as a contributing factor in hard-to-treat diabetes, intending to integrate the Noxious Nine into clinical practice to improve patient outcomes. These findings represented a significant breakthrough in the understanding and management of complex T2D cases, with an FDA-approved treatment available for affected patients.

Relevant disclosures for DeFronzo include Corcept Therapeutics, AstraZeneca, Novo Nordisk, Alynylam Pharmaceuticals, and others.

DeFronzo R. Noxious Nine. Presented at the 22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC). Los Angeles, California. December 12-14, 2024.

Iapoce C. Mifepristone Notably Reduces HbA1c in Treatment Phase of Catalyst Trial. HCP Live. December 12, 2024. Accessed December 13, 2024. https://www.hcplive.com/view/mifepristone-notably-reduces-hba1c-in-treatment-phase-of-catalyst-trial.

Ralph DeFronzo, MD, discussed the evolution of his Ominous Octet concept to the Noxious Nine, highlighting the role of hypercortisolism in difficult-to-control type 2 diabetes (T2D). Initially focusing on insulin resistance and beta-cell dysfunction, the model expanded to include additional factors like obesity and excess glucagon secretion. The CATALYST study found that 24% of patients with challenging T2D have elevated cortisol levels, significantly impacting glycemic control. Mifepristone treatment showed a 1.5% reduction in HbA1c, suggesting a new therapeutic approach for these patients.

Ralph A. DeFronzo, MD discusses the Noxious Nine and the impact of hypercortisolism on difficult-to-control type 2 diabetes.








Ralph DeFronzo, MD 

Ryan Oakley, MD, takes a closer look at the recent history of ketamine in depression. He also explores the differences between ketamine and esketamine.

Ketamine for the Treatment of MDD

 I'm going to be talking about the interventional options that move a little bit away from direct electrical stimulation, using a more advanced neurochemical intervention. I would be surprised if most of you haven't at least heard of ketamine at this point as being used for mental illness in some way. It's all over the news, it's being marketed for a lot of different things. We're going to discuss a little bit about what it has actual evidence for and clear some of that up, including talking about what the FDA just released to combat some of that marketing. We're also going to talk about the evolution and the creation of the FDA-approved insurance-covered form of ketamine, which is esketamine, and how we use that in our clinics as an intervention.

So, what's special about ketamine, why is this being developed as an interventional treatment? First, to understand where ketamine is right now what it's been used for, its primary use is the procedural anesthetic and medicine. It started being explored for depression specifically based on some animal studies that showed that, when intervening on the glutamate system, the animals depressed behaviors improved, also based on some human clinical studies with medications that act on the glutamate system, like lamotrigine or alprazolam, also found to have some antidepressant activity. So then, a group decided to see if we could intervene directly on the glutamate system with an NMDA antagonist, like ketamine, to see what kind of effect would that have on depression. This group did a study, a randomized controlled trial, double-blind crossover study, and showed that it did, in fact, have a pretty dramatic, rapid, and sustained antidepressant activity. It was then explored a lot more as a treatment for depression.

We talked about ketamine a little bit. Esketamine was developed later. Essentially, ketamine is a combination of two different mirror images of a molecule. Esketamine is one of those mirror images of the molecule that they've designed and created to be delivered intranasally in an office setting, which sort of improves its scalability (ie, how easily we can deliver this treatment). So that's where esketamine is. “Es” is actually the name of the mirror image of ketamine, [and] this how it gets its name.

So, breaking down the difference between ketamine and esketamine, the biggest one is which one's actually insurance-based, which one has approval. Ketamine is not approved by the FDA for any kind of mental health treatment at this point. It's also not covered by insurance. Esketamine is approved by the FDA for treatment-resistant depression or major depression with suicidal ideation. The FDA recently put out a warning on compounded ketamine, because ketamine is getting marketed almost like a snake oil treatment for all the different types of mental illness where there's not a lot of evidence to support it (except for in depression, IV formulation, and a specific way of delivery). Whereas esketamine has evidence, we have a well-defined means of how to deliver it.

[What are] other differences between them? Ketamine, the drug itself or the medication is actually quite inexpensive. Esketamine, the drug, is actually quite expensive. However, insurance covering esketamine actually makes it more affordable for patients, whereas ketamine treatments, you're not just paying for the medication, you're paying for staff, you're paying for monitoring, paying for IV, all these things. It actually becomes less affordable for the patient, whereas esketamine is a very affordable option for people with treatment and depression. Other things to note is that there's no federally mandated program that tells us how to use ketamine. There are no guidelines for it. Esketamine does have guidelines. Ketamine doesn't have a risk evaluation mitigation system. So, we don't have a place where we can find out more about the side effects of how safe ketamine actually is, whereas esketamine does have that. We're continually monitoring how safe it is, and also able to update information for patients to make sure we deliver it the most safe way possible.

Transcript was AI-generated and edited for clarity. 

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