Obesity is a risk factor for cardiovascular disease, but preventive cardiologists may face challenges in counseling a patient on a healthy body weight and strategies to achieve this goal.

2022 American Society for Preventive Cardiology Meeting

, Robert Kushner, MD, Feinberg School of Medicine, Northwestern University, presented a talk on how to treat obesity as a cardiovascular risk factor, referring to it as ‘the one that got away.’

The talk highlighted data that support obesity as a risk factor, including disability-adjusted life years (DALYs) and the effects on the heart, such as heart failure with preserved ejection fraction (HFpEF).

“I am also talking about the benefits of weight loss, not only on reducing cardiovascular risk, but also improving metabolism as it relates to insulin sensitivity and reducing insulin resistance as it relates to metabolic syndrome,” Kushner added.

He additionally discussed how clinicians can better help patients manage their weight by using targeted strategies, such as self-monitoring, meal plans, support and accountability. Kushner described the foundation of obesity treatment as lifestyle management, including diet and exercise, as well as stress reduction and lack of substance abuse.

However, the excitement for Kushner has come in the form of adjunctive pharmacotherapy. He noted that the field is at the verge of a second generation of medicines for obesity, primarily mimicking gut hormones, such as GLP-1s. In addition to treating diabetes and lowering blood sugar, the effects of these agents on appetite have led to double digit weight loss, including up to 20% weight loss, Kushner noted.

“It's not only an incretin hormone for diabetes, but in improving appetite, but also affecting other cardiovascular risk factors, effects on the kidney blood pressure and blood clotting,” Kushner added.

Kushner discussed the continuum of options in obesity management, from lifestyle changes to diet and exercise, but also noted the more aggressive treatments for obesity. The first, as noted above, is pharmacotherapy, but the other is bariatric surgery. He added that the surgery is the most effective treatment for patients with obesity, and that typically leads to significant endurable weight loss.

“I think it's important when we see individuals and we present all the options to them really from the very beginning about what is going to be the most effective treatment,” he said.

For a patient with high risk of cardiovascular disease and a corresponding body mass index (BMI) of ≥40, Kushner is potentially thinking about bariatric surgery for that individual.

“They don't have to fail lifestyle management and then fail pharmacotherapy to then bring up bariatric surgery,” he added. “We want to bring the most effective treatment for that patient as early as possible.”

Kushner further discussed the awareness of social determinants of health in obesity treatment. These social determinants are particularly affecting those who suffer from obesity or excessive weight due to a lack of resources, access to healthy foods, and others necessary to promote health in a community.

He noted that those who are most affected are often of lower socioeconomic status, particularly African-American females who have the highest prevalence of severe obesity in the United States.

“When we make recommendations to individuals and minority groups, we have to think about access and affordability when we're recommending treatments,” Kushner said. “Unfortunately, due to health care resources, a lot of the exciting medications that are being developed, are not affordable or not covered under certain health plans, so we have to be very aware of that and sensitive to the needs.”

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Dr. Kushner discusses obesity as a risk factor for CVD and how preventive cardiologists can better target weight management to support patient health. 

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 because that’s the core principle of disease that makes it so exciting and interesting on our standpoint—to treat, see, understand, and learn about. But that can also make it difficult in terms of thinking about that patient aspect of the burden. We oftentimes think about the disease as mild, moderate, or severe, and they’re very clean buckets. Some of the signs you’ve told us about allow us to make some of those judgments. But when you think about all the different heterogeneous clinical domains beyond the skin signs, when you think about symptoms, quality-of-life burdens, comorbidities, all things you touched on, a lot of this can change what you might see on the skin—mild, moderate, or severe—and that can have a lot of big implications on treatment, which we’ll talk about in a bit.

I want to come back to you, Britt. Maybe you can tell us a little about not exact numbers but what your feelings on the prevalence of atopic dermatitis in pediatric patients? You mentioned that it’s 1 of the things you commonly see in dermatology. Is this really common? Is this something that a lot of pediatric practitioners outside dermatology are seeing as well? What are your thoughts on what happens in the long run as these kids grow up?

It’s common, especially in the younger population. Up to a quarter of patients or kids, or even more, will have AD [atopic dermatitis]. Depending on where you live and the access to dermatology, a lot of these kids are still with their pediatrician. Some are unfortunately not being appropriately managed, or there’s this idea that they’re going to grow out of it, so they tolerate it. Maybe they’ll grow out of it, but it’s not OK for someone to be miserable. As the treatment landscape is evolving, part of our job as dermatologists is to educate. We have more tools now. When you sent kids to dermatology before, they weren’t coming back with a lot that was helpful or different from what you could offer. But all of a sudden, we have more options. This is a disease that kids don’t have to live with anymore.

The way we think about it needs to shift a little bit too. To your point about mild, moderate, and severe, we have to remind ourselves that just because someone is not erythrodermic, doesn’t mean they’re not miserable. We see the spectrum. Just because patient A doesn’t look as bad as patient B, that doesn’t mean it’s not having a big impact on their quality of life. It’s all about the patient experience. Now we have things to offer them that have a better safety profile. When our choice was cyclosporine or mycophenolate, maybe we tolerate the higher disease severity because we’re weighing risk and benefit, but now we need to shift our framework because we have these options. Many people aren’t being appropriately treated and honestly, in kids, their trajectory is sometimes altered by this. It’s important that we step up and educate and treat our patients a little more aggressively.

How often are you seeing that, Dr Lio? Some parents or caregivers don’t want to treat their child, and they hope they’re going to outgrow the disease or that it’s just a little skin thing they’ll get over?

I definitely see that a fair amount. Usually, they’re not dismissing the disease, but they’re afraid of the potential side effects of medications. They recognize that it’s a huge burden. It affects quality of life, and that’s usually why they’re showing up. At the same time, there are many trepidations about starting some of the medicines, which admittedly can sound pretty off-putting. Even with topical corticosteroids, our old friends since the 1950s, if you start reading about what they can do, sometimes there’s a hesitation to start therapy. I often try to convey that even though many patients will get better in time, and certainly some will outgrow their disease, an awful lot of patients still maintain it. In particular, it seems as though the more severe patients will continue to suffer from the disease even into adulthood. I have a whole group of patients who are bitter because everyone throughout their young lives said, “Don’t worry, you’ll grow out of this.” Now they’re in their 20s, 30s, or 40s and saying, “Here I am decades later, and I’m still miserable with this disease.”

I’m a big proponent, as Britt was saying, of treating early and aiming for excellent disease control. Not only do you automatically win by getting people better, but you take away that suffering, pain, disruption of sleep—all those pieces. There may be a hidden benefit, which is that we may be able to modify the course of the disease. If we can do that—not only atopic dermatitis but maybe some of the allied and comorbid allergic-type diseases, those comorbid conditions—that could be a huge win for all involved.

Experts in dermatology comment on the heterogeneity of atopic dermatitis and how this affects clinical practice decisions, patient quality of life, and disease burden.

Atopic Disease Heterogeneity and Physician Awareness

 titled “Expert Perspectives in the Management of Pediatric Atopic Dermatitis.” I’m Dr Raj Chovatiya, and I’m an assistant professor of dermatology and the director for the Center of Eczema and Itch at the Northwestern University Feinberg School of Medicine in Chicago, Illinois. Joining me in this session are my esteemed colleagues. We have Dr Britt Craiglow, who practices at the Dermatology Physicians of Connecticut. She’s an adjunct associate professor at the Yale School Medicine in New Haven, Connecticut. And we have Dr Peter Lio, who practices at the Medical Dermatology Associates of Chicago. He is also a clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine in Chicago, Illinois. Welcome everybody and let’s jump on into it.

Today we’re talking about all things pediatric AD [atopic dermatitis]. We couldn’t have a better panel to talk about some of the aspects facing us in terms of pathophysiology, burden, and some of the exciting new evolutions in treatment. To start, I want to get a bit of an overview about the disease itself, how we diagnose this in our kids, and how this might be different compared with adults as well. The first question I’ll toss over to Dr Lio. Tell me a little bit about your feelings about pathophysiology of atopic dermatitis and how all this has evolved over time when we think about the disease. When I talk to my patients, I think about the barrier and the immune system. Maybe you can tell us more about how all that works together.

Thank you. It’s been such an interesting journey learning more about this disease, especially looking at ancient conceptions of atopic dermatitis and how this relatively modern disease still does have some roots that go far back, maybe as far back the 

in ancient Egypt. A lot of interesting stories over the years. We’ve refined our understanding to encompass what I think of as the 5 pillars. What’s interesting about these 5 pillars is that they’re really part of a vicious cycle that can develop. You already mentioned 2 that are fundamental. The skin barrier, we know that it’s leaky, as I like to tell my patients. That impaired barrier that allows water to come out also allows allergens, irritants, and pathogens to get in. Then we have the inflammation aspect as well. That can be a primary cause. Some people just seem to be hypersensitive—the immune system going crazy—but it also can be secondary. When those allergens and irritants get in, the immune system very appropriately reacts to that.

There are a couple of other pillars worth pointing out. One is the microbiome. We’re learning more that the microbiome is not just a bystander. It’s not just a colonizer hanging around. It can be a primary driver, particularly 

 bacteria. It can produce a bunch of toxins that can drive barrier damage and inflammation, which is pretty amazing. Then we have the nerve endings themselves. This is an exciting area, thinking about itch and not only the morphology of the nerve endings—that they can get more dendrites—but also the physiology of the nerve endings. Their threshold for itch drops down over time. We can see this sensitization or potentiation of these pathways in the entire nervous system through the DRG [dorsal root ganglion] and into the brain. Finally we have the neurobehavioral aspect. That’s the mind-body aspect of this disease. We know behavioral things like the itch-scratch cycle, anxiety, poor sleep, and all these can feed back in. Those 5 give us a good sense of all the aspects of this disease, at least from 1 take.

I couldn’t have put it better. When you think about the disease, historically there was this concept that this is a childhood disease and it doesn’t happen much after. A lot of this has been turned on its head. Dr Craiglow, you can tell us a little about the typical age of onset? Why was this the predominant theory, and how has it changed? What are some of the presentations you’re looking for in terms of the disease in a pediatric population?

In pediatric dermatology, atopic dermatitis is our bread and butter. Most patients with AD are going to have an onset in childhood, usually pretty early. The majority has onset before age 6 or so. That’s an important point. If you have someone coming in with what you think is onset atopic dermatitis, you want to make sure it’s AD and that you’re not missing a contact allergen, CTCL [cutaneous T-cell lymphoma], some other diagnoses that may be a mimicker.

But for AD in kids—it doesn’t look the same in everybody—it’s a pretty straightforward diagnosis. We think about the morphology and distribution evolving over time, where oftentimes infants come in and have those bright-red stoplight cheeks, and they have involvement primarily of extensor surfaces. That can change a little as they get older to more flexural involvement. We learn that AD is red, dry, oozy, and itchy, and it’s oftentimes, but it’s important to note that it can be clinically very heterogeneous. Especially in darker skin types, it may not have that classic appearance. We see sometimes this monomorphic follicle-based papules which are clinically not as dramatic but can be very itchy and uncomfortable.

Sometimes it’s more of a prurigo nodularis type of picture. If a patient is itchy and has skin lesions, you have to be thinking about AD. Especially in younger kids, oftentimes there’s a family history. They may also have food allergy, or they’re going to have that whole atopic picture, so it makes a diagnosis fairly straightforward. It’s not a 1-size-fits-all thing. It’s important to keep that in mind as we see patients, especially if they’re presenting with more of the less classic presentations.

Raj Chovatiya, MD, PhD; Brittany G. Craiglow, MD; and Peter A. Lio, MD, provide insight into pediatric atopic dermatitis, focusing their discussion on the pathophysiology, prevalence, and disease symptomology.

Pediatric Atopic Dermatitis: Pathophysiology, Prevalence, and Symptomology

: What we’re driving toward is something called, microbiota-based live biotherapeutic products. This is the FDA moniker for forms of fecal transplant. We are at a really exciting point right now because there are 4 products going through the FDA process. Two have finished phase 3 trials, including RBX2660 and SER-109, and 2 have completed phase 2 studies, all with positive results. Now, there are certain similarities among all of the studies I’m going to talk about. One, all of the studies involve patients with recurrent 

. Two, all of the studies required that patients receive a standard course of antimicrobials prior to the transplant; you have to control that vegetative phase before you try to eradicate the spore phase. Three, all of these studies had an 8-week assessment for recurrence. Let’s talk briefly about these products.

The first product I’d like to talk about is something called, RBX2660. This is a broad consortium microbiota-based live biotherapeutic. That means there’s a wide array of microorganisms including both spore and nonspore forming bacteria within the formulation. RBX2660 is rectally administered. In order to understand the phase 3 trial, we have to understand the phase 2 trial. The phase 2 trial that assessed RBX2660 included patients with 2 or more recurrences of 

 infection. They all received standard of care antimicrobial, and then they were randomized to 1 of 3 groups. One group was given 2 doses of placebo approximately a week apart. The next group was given a dose of RBX2660 followed a week later by placebo, and the third group was given 2 doses of RBX2660 rectally administered 1 week apart. They were followed for 8 weeks for recurrence and 24 months or 2 years for safety. As a result of this trial, a single dose of RBX2660 proceeded to the phase 3 trial. The phase 3 trial included patients with 1 or more recurrence of 

. All received standard of care antimicrobial, and then they were randomized to receive a placebo, or a single dose of RBX2660. They were followed for 8 weeks for recurrence, and 24 weeks or 6 months for safety.

This trial was important because it performed a Bayesian analysis. The reason I introduced the phase 2 study design was the similarity between the phase 2 and phase 3, with similar diagnostics, same intervention, and similar follow-up for recurrence. As a result, a Bayesian analysis allows you to leverage 2 studies’ data together to produce a larger study if the intervention of placebo and the intervention of interest, in this case RBX2660, show similar efficacy across both trials, and that of course was achieved here. Within the phase 3 trial, the quoted efficacy for RBX2660 was 70.4% compared to 58.1% in the placebo arm. The posterior probability of superiority was 0.986, showing a statistically significant difference between RBX2660 and placebo, favoring the RBX2660. So this product is most likely going to be reviewed by the FDA soon and has very exciting results.

Another exciting product is SER-109. This is a capsule formulation that says, look, we have a deficiency of the Bacteroidetes and Firmicutes, causing dysbiosis. Why don’t we supplement the Firmicutes spores in a capsule formulation? This is administered as 4 capsules daily for 3 days, following a standard of care antimicrobial. The phase 3 trial data from this product was published in the 

earlier this year. Within this trial, patients with 2 or more occurrences of 

 were randomized to all receive standard of care antimicrobial, and then either placebo or SER-109 at 4 capsules daily for 3 days, following that standard of care antimicrobial. They were then followed for 8 weeks for occurrence and 24 weeks for safety. The overall efficacy for SER-109 within this analysis was 88% versus 60% in the placebo arm, showing statistical significance. This product also will likely be considered by the FDA over the coming months to a year.

There are 2 products that have completed phase 2 trials. One is a product called CP101. This is a capsule formulation that is a broad consortium, or a wide array of microorganisms. This is administered as 10 capsules on a single day following standard of care antimicrobial. The phase 2 study design for this product included patients who had 1 or more occurrences of 

; all received standard of care antimicrobials. Then they were randomized to either the 10 capsules of CP101 or a placebo, followed for 8 weeks for recurrence, and 24 weeks for safety. The efficacy within the CP101 arm was 74.5% versus 61.5% in the placebo arm. This also achieved statistical significance, and this is proceeding into a phase 3 trial, which is ongoing.

The final product is a bit of a different product. This includes 7 bacterial strains, a so-called defined consortium. These bacterial strains originated from the human digestive tract, but now are synthetically reproduced. At a major international conference in San Diego, California, in May 2022, the phase 2 trial data were presented, and this was a dose-ranging study for patients with 1 or more recurrence of 

. All received standard of care antimicrobial, and then were randomized to either a placebo for 14 days, a low dose of this product called VE303 for 14 days, or a high dose of VE303 for 14 days. Overall, the lower dose did not achieve statistical significance, but the higher dose had an efficacy at 8 weeks of 86.2% compared with 54.5% in the placebo arm. So this too will likely proceed to a phase 3 trial.

 now is emerging and it’s evolving. Previously, we just had standard of care antimicrobials, and those work relatively well, but we see high rates of recurrence after completion of therapy because that spore phase is regerminating to the vegetative phase. With the foundational clinical trials considering fecal microbiota transplantation and the rudimentary technology and techniques, we saw nice efficacies. But the predictability of safety and efficacy due to the heterogeneity of these products led us to scratch our heads a bit and not apply this more broadly. As we go into this next phase of microbiota-based live biotherapeutics, we have several exciting products, including RBX2660, SER-109, and a little further down the pipe, CP101 and VE303. The future in the world of fecal microbiota transplantation and now the more sophisticated microbiota replacement therapy is incredibly bright, and I’m so excited that you joined us today for this learning session.

Dr Feuerstadt discusses data with 4 emerging microbiota-based live biotherapeutics for treatment of rCDI: RBX2660, SER-109, CP101, and VE303.

Emerging Treatments for Recurrent C diff Infection

: The focus of this discussion will be on fecal microbiota transplantation and microbiota-based live biotherapeutics. The microbiota is dysbiotic in patients who have 

, meaning there are deficiencies. Those deficiencies lead to initial infection, as well as recurrent infection. Without further intervention, those deficiencies need to be regrown or resupplemented by foods and by patients themselves. Unfortunately, that results in 25% to 35% of patients initially recurring with 

, 40% to 50% having a recurrence beyond the first recurrence, and up to 60% being recurrent beyond the second recurrence. What we’re seeing here is that the microbiota has a hard time reproducing and a hard time filling in those cracks. What can we do? We can supplement that microbiota from an outside source, or perform a fecal microbiota transplantation.

What are the data for fecal microbiota transplantation? There have been several pivotal trials over the last decade, and I call it the “ark of efficacy.” Starting in 2013, the first prospective, randomized controlled trial considering patients with recurrent 

 who received a fecal transplant was published in the 

by [Els] van Nood, MD, and colleagues. Within this trial, patients with recurrent 

 were randomized to either receive vancomycin followed by a nasal enteric transplant, compared with vancomycin and bowel lavage, or vancomycin alone. In fact, this study was stopped at interim analysis due to futility of the vancomycin arms. Efficacy in the fecal transplant arm was 81.3% versus 23.1% in the vancomycin and bowel lavage, and 30.8% in the vancomycin alone. What was most important about this study was firstly, that the fecal transplant seemed to work well, but that they did a microbiota analysis. They looked at the microbiota in the donors pretransplant, in the recipients pretransplant, and finally, in the recipients post-transplant. They showed that after the nasal enteric transplants, the diversity of the microbiota, the deficiencies or the dysbiosis seen in the microbiota, were properly supplemented through a nasal enteric transplant. We theorized that by performing a transplant, we would fill in those cracks, and that’s what was seen.

Following this, there was a whole slurry of different studies looking at fecal transplant in patients with recurrent 

 infection. Quite a few of them were case series. Some of them were prospective, peaking in 2017 with a meta-analysis by Mohammed Quraishi, MD, and colleagues. Within that meta-analysis, they looked at 7 prospective trials and 30 retrospective cases series. They found an overall efficacy for fecal transplant in patients with recurrent 

 of 92%. We were super excited; we thought that we were potentially going to be curing patients of this recurrent disease. Unfortunately, with better structured studies, we learned that the efficacy was still excellent, but it wasn’t quite the efficacy of 92%.

A nice meta-analysis was published in 2019 that looked at this by Darrell S. Pardi, MD; Sahil Khanna, MBBS, MS; and Raseen Tariq, MD. Within their meta-analysis of 13 studies and 625 total patients, they only included studies that had a control group. This is a basic premise for clinical trials, but in the fecal transplant world, it was something that was a bit of a leap compared to the 2017 Quraishi meta-analysis. Within this updated meta-analysis that included only trials with a control group, the overall efficacy for fecal transplant in patients with recurrent 

 was 76.1%. So not quite that 92%, but still really good. However, when they drilled deeper and looked at open-label trials, open-label trials had an efficacy of 82.7%. Randomized controlled trials had 67.7%, which is still is excellent, but again, not quite that 92% that we were looking at previously. The 67.7% is largely a target for what we’re going to see broadly, if and when fecal microbiota transplantation gets more adaptable to the general population, and the general clinical population is able to use this.

Now, these foundational trials were incredibly important and gave us a lot of insight into the ability for fecal transplant to shut down this burdensome cycle of recurrence. However, these studies weren’t perfect either. There was heterogeneity in the efficacy analysis and in the safety analysis. Most importantly, there was heterogeneity with regard to the treatment itself. A fecal transplant in San Diego might be different than one in New Haven; it might be different than one in Seattle, and it might be different than one in Miami. Why? Because the donor screening processes were different. The processing of the actual samples was different. Finally, the administrative techniques were different. Heterogeneity was classified and characterized by…et al in a publication that pivoted our thoughts around this, saying that fecal transplant following a standard of care antimicrobial can certainly work, but we need to have a more codified structure in the data analyses for these and more predictable products. This means consistent products, safety analysis, efficacy analysis, but most important, consistent donor screening, processing, and finally, consistent administration.

A gastroenterologist summarizes foundational trials that led to the use of fecal microbial transplant for treatment of rCDI.

Foundational Trials for Fecal Microbial Transplantation for C Diff Infection

:My name is Dr. Paul Feuerstadt, MD, and I am an assistant clinical professor of medicine at the Yale University School of Medicine and an attending gastroenterologist at the PACT Gastroenterology Center. I’d like to welcome you to this learning session today, a primer covering 

 infection with a focus on microbiota-based live biotherapeutic products.

 is a major problem in the United States. In fact, it’s estimated that 500,000 individuals will test positive on an annual basis, leading to a significant burden on the health care system, but most importantly, a significant burden on the patient population. It’s estimated that 25% of all individuals who are diagnosed with 

 and receive a standard of care antimicrobial, an appropriate treatment, will recur. Of those who recur, up to 40% will recur again, and up to 60% thereafter as patients get caught in the cycle of recurrence, after recurrence, after recurrence.

Why do so many patients recur? In order to understand recurrences, briefly, we have to understand the basic structure of the life cycle of 

; one is the vegetative phase. The vegetative phase is susceptible to gastric acid and alcohol-based hand sanitizers. Plainly stated, if it comes in contact with these things, it gets wiped out. The vegetative phase releases 2 main toxins, toxin A and toxin B, that most commonly stimulate the abdominal pain, diarrheal syndrome, and fevers associated with 

 infection. Alternatively, the spore phase is a much more resistant phase. The spore phase is resistant to gastric acid and alcohol-based hand sanitizers. In fact, the spore phase most commonly remains within a patient’s system after antimicrobial treatment, either being released in the stool causing transmission from person to person, or staying within the system and reconverting back to the vegetative phase, causing a recurrence.

? Classically, they swallow the spore phase; it’s resistant to their gastric acid, gets through their gastric acid into their small bowel, where a process called germination occurs. Germination is the conversion from the spore phase to the vegetative phase. The vegetative phase then multiplies, divides, and multiplies some more as it builds an army of sorts heading toward the colon. But I’m a gastroenterologist, and I think the colon is a brilliant organ, and the colon is a brilliant organ because it has its own defense system, independent of the blood-borne defense system that protects it. What is that defense system? The microbiota or colonization resistance. What classically weakens colonization resistance? Amoxicillin, ampicillin, clarithromycin, fluoroquinolones, and cephalosporins. We weaken the colonization resistance or create a so-called dysbiotic state that allows the 

 to proliferate. The vegetative phase releases those toxins and stimulates the diarrheal syndrome and the symptoms that cause patients to be uncomfortable.

As we understand that basic pathophysiology of 

 infection, we need to contextualize the treatment of 

 infection involves antimicrobials. Antimicrobials largely control the vegetative phase. However, the spore phase is not usually impacted by these antimicrobials. This is why when patients are on antimicrobials, their symptoms improve. However, that spore phase is largely eradicated by the microbiota, but the microbiota is so-called dysbiotic or weakened prior to 

, their microbiota is even further dysbiotic or further weakened, leading to recurrence after recurrence after recurrence. Why? Because without further intervention, the microbiota needs to regrow itself in order to supplement the deficiencies, and it does it pretty well, but it doesn’t do it very well. As a result of that, those deficiencies persist and patients get recurrent because the score phase is able to reconvert to the vegetative phase.

When we think about antimicrobials, it’s important to go back and understand the guidelines, and the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America [IDSA/SHEA] updated their guidelines in 2021. With this update, there is a new favored treatment for initial infection with 

. That new favored treatment is fidaxomicin; this given at 200 mg twice daily for 10 days is the preferred treatment of an initial infection. An acceptable alternative is vancomycin, at 125 mg 4 times daily for 10 days. As you’ve noticed, metronidazole has largely been phased out. For an initial infection, metronidazole is only recommended when neither fidaxomicin nor vancomycin are available, the patient’s white blood cell count is less than 15,000, and their creatinine is less than 1.5 mg/dL. For that first recurrence, the IDSA/SHEA guidelines recommend, again, preferred treatment with either fidaxomicin for 10 days, or fidaxomicin 200 mg twice daily for 5 days, followed by 1 tablet every other day, day 7 through 25. An acceptable alternative is vancomycin in a tapered and/or pulsed fashion.

Finally, for patients who fail metronidazole initially, vancomycin at 125 mg 4 times daily for 10 days is recommended. Within this first recurrent group, the first so-called add-on therapy was recommended, and that therapy is a product called bezlotoxumab. Bezlotoxumab is a fully humanized, monoclonal antibody designed to bind toxin B in a very specific way. By doing that, and by infusing bezlotoxumab, it’s a onetime infusion, during the standard of care antimicrobial, recurrence rates might be reduced. That is what the MODIFY-I and MODIFY-II trials show, and that’s how this entered the guidelines. For the second recurrence and beyond, pretty much the recommendations are to use what you haven’t used already, either a fidaxomicin regimen, vancomycin in a taper and pulse regimen as well, or vancomycin and a 10-day treatment course followed by a chaser of rifaximin. Those are the antimicrobials, however, there are 2 add-on therapies for second recurrence and beyond, which is either bezlotoxumab, or fecal microbiota transplantation.

Dr Paul Feuerstadt provides an overview of Clostridioides difficile infection and why it is challenging to manage recurrent C diff infections (rCDI).

Clostridioides Difficile Infection Overview and Management

The need for ongoing, continuous data is important for studying virtually any disease, including 

 (NAFLD) and nonalcoholic steatohepatitis (NASH), neither of which have treatments approved by the US Food and Drug Administration (FDA).

That is why a study like TARGET-NASH is important because it allows investigators to collect data on a longer period of time and monitor different attributes and data points from patients with NASH or NAFLD.

, Arun J. Sanyal, MBBS, MD, Director of Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Interim Chair of Division of Gastroenterology, Hepatology, and Nutrition, Z. Reno Vlahcevic Professor of Medicine, Physiology, and Molecular Pathology, Virginia Commonwealth University School of Medicine, discussed how important it will be to continue to study and examine patients with these liver disorders and discover how patients ultimately change over time in an effort to improve treatments, screenings, and care.

“You have to remember, to do these types of things you have to have a lot of data and in usual clinical practice people might come in once a year,” Sanyal said. “There’s a paucity of data and here we have patients across a spectrum of clinical centers and data will be collected as part of real-world evidence.”

Recently, investigators presented new results as part of TARGET-NASH showing longitudinal trajectories of alanine aminotransferase (ALT), a common liver biomarker, were stable among patient with NAFLD.

The data was presented at the International Liver Congress (ILC) 2022 in London and is part of TARGET-NASH, an observational study of participants with NAFLD and/or NASH in usual clinical practice.

Dr. Sanyal talks about the importance in having ongoing real-world data for NAFLD and NASH. 

Arun Sanyal, MD: The Importance of Continuous Data for NAFLD

 field celebrated the 100th anniversary of the insulin discovery last year—a landmark innovation not only in endocrinology and cardiometabolic disease, but medicine overall. A full century later, the impact of insulin therapy is ineffable in diabetes management.

That is not to say the field is deprived of any other innovations.

Last month, diabetes experts and specialists from the Duke Health collaborated with 

 on a State of the Science Summit program titled, “Institutional Perspectives in Type 2 Diabetes: Contemporary Approaches to Insulin Treatment.”

The paneled presentation was led by chair Jennifer Green, MD, diabetologist and professor of medicine at Duke University Medical Center.

, Green discussed the 3 classes of technology that have delivered innovation for modern type 2 diabetes care.

Starting with insulin pumps, Green described the needs of the various patients with unstable or inadequate glycemic control, despite use of an intensive subacute insulin regimen. “Particularly if they have problems with hypoglycemia at transition to insulin, delivery through an insulin pump would always be a reasonable consideration,” Green said.

Green also praised the accessibility and benefit of continuous glucose monitoring devices for patients with ≥1 daily insulin injection. “I do think in many circumstances these are incredibly important from a safety perspective,” she said. “But I think the real advantage is in alerting people to hypoglycemia, particularly in patients who don’t manage hypoglycemia well. They can be life-saving devices, frankly.”

Lastly, Green described smart insulin pens as capable of working in concert with glucose sensors to provide real-time, accurate insulin doses. “That can be very, very helpful in reviewing someone’s data to really understand what was administered and what might not have been administered so that the regimen can be changed safely and effectively,” she said.

Finally, on the subject of navigating these armaments for the appropriate patient, Green discussed the benefit of the American Diabetes Association (ADA) Standards of Care.

“They do offer a condensed version which is geared toward primary care doctors in general,” Green said. “I would also say to really discuss your patients who have a need for diabetes specialty care with those diabetologists, endocrinologists or other specialists who they go to to provide that care so that it’s a learning experience.”

Jennifer Green, MD, discusses the benefit of relatively new innovations including continuous glucose monitoring and smart insulin pens.

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