Oroteinuria Reduction in Long-Term Kidney Damage Prevention

How does the reduction of proteinuria factor into the broader treatment goals for IgA nephropathy, and what evidence, if any, supports proteinuria reduction as a critical goal in preventing long-term kidney damage?

Biomarkers and clinical indicators play a crucial role in predicting disease outcomes, offering insights into disease progression, treatment response, and patient prognosis. These indicators can be genetic, molecular, or cellular, and are often identified through advanced diagnostic techniques. For instance, specific gene mutations or protein expressions can indicate the likelihood of disease recurrence or metastasis. Additionally, clinical indicators such as tumor size, stage, and patient health status are integral in assessing outcomes. Personalized medicine leverages these biomarkers to tailor treatment plans, enhancing therapeutic efficacy and patient survival rates.

Panelists discuss how the reduction of proteinuria is integral to the broader treatment goals for IgA nephropathy, highlighting evidence that supports its role in preventing long-term kidney damage.

Proteinuria Reduction in Long-Term Kidney Damage Prevention

Brendon Neuen, MBBS, PhD

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: 

We’re comingto the end of this discussion, but I want to talk about unmet needs in PBC [primary biliary cholangitis]. What are some unmet needs? I’m going to have everyone comment, but I’m going to start with you, David.

This was a lead-in to say that transplantation for patients with PBC is an unmet need. They’re not well served by our current allocation system, and I’ve implored some of our UNOS [United Network for Organ Sharing] colleagues to consider itching in the malignant, life-altering aspect of pruritis to be something that we incentivize for transplant. Transplant is supposed to make your life longer and better, and many of these patients with recalcitrant pruritus from PBC deserve quality therapy. That’s where I see the biggest unmet need. I don’t think we do great in our transplant world. That’s a bigger question to answer. I’m hopeful that these new therapies and some of the emerging therapies may be able to treat some of our patients who aren’t candidates for obeticholic acid or second-line therapy as we try to prevent them from progressing to such a stage.

That’s a good point. There’s concern about patients who have decompensated liver disease. Obviously, they can’t receive obeticholic acid. With fibrates, there are some concerns and warnings about liver or kidney toxicity. Clearly, that’s the population where there’s a big need. I’ve had 3 patients in my career who I was able to get either prior to MELD [model for end-stage liver disease] and requiring exception points or during MELD with exception points for refractory life-threatening pruritis, 2 of whom were considering suicide. Those patients would not be eligible for exception points in this era. It’s uncommon, but it’s a huge unmet need. Ed, what do you think are the unmet needs in this disease?

Something we looked at in our clinic is ethnic disparities in PBC. We found that our Latino population who had PBC came at a much later stage of disease. Most of them have cirrhosis. David, you mentioned patients with PBC languishing in clinics. Increasing awareness of PBC and screening using the antimitochondrial antibody in certain ethnic groups or communities would be of value.

Like many things in liver disease, Kris, they’re all out of unmet needs. First, there’s an unmet need regarding the education of practitioners in how to diagnose this early. There’s an unmet need in terms of having more effective primary therapy in the first place for patients with PBC. There’s an unmet need for the treatment of the profound fatigue that some patients have with this disease. Even if they don’t have cirrhosis, it’s a major quality-of-life issue for them. There’s an unmet medical need for the pruritis. The pruritis doesn’t always correlate with the advance, with the stage of the disease. That’s also a misunderstanding. Patients can have moderate pruritis, which does affect their quality of life, but it’s not enough to need a transplant, and their liver disease isn’t so advanced. We know we could do better with therapy. So, there are a lot of unmet needs in PBC.

I agree, and your point about pruritis and symptoms not being correlated with disease severity is important to recognize. Some patients, as they start having more symptoms, are petrified, and their fatigue is getting worse. They think they need to get on a liver transplant list.

For patients with PBC, 1 of the extrahepatic manifestations is they can have very profound and aggressive osteoporosis. The guidance documents are clear that patients should have periodic bone densitometry when they have PBC. This, too, doesn’t correlate necessarily with the stage of their liver disease, and you can’t wait until patients are having spontaneous pathological fractures to identify this. The audience should also know in a patient with PBC that they are or should be recommending periodic bone densitometry to look for osteoporosis or even osteopenia.

At a minimum, your patient with PBC who comes into the office every 6 months or 1 year should have a vitamin D test with their standard labs. That’s a guidance, but it’s often not done. We added it to our standard order set for patients with cholestatic liver disease, so other providers would do it. That’s the best and easiest screening tool to identify higher-risk patients.

That’s an excellent point. Fractal vitamin deficiency isn’t necessarily seen only in patients with jaundice, so we do that routinely when we first see the patient. Sonal, you get the last word on unmet needs for education and for patients or clinicians.

I’ll piggyback on what Steve said. As physicians, we focus on normalization of the alkalis or goals of preventing and disease prevention, which are understandable and obviously important. But from a patient perspective, what affects their day to day is their quality of life. If we can improve that, in combination with these new therapies, that will prevent disease progression. That will be huge.

That’s great. That hour and a half went by fast. I appreciate the chance to share thoughts and clinical experience. Thanks to all of you for this rich and informative discussion. Before we conclude, I’d like to get some final thoughts. Everybody gets 30 seconds. Let’s start with you, Steve.

The practitioners in the audience should understand that although this is an uncommon disease, it’s not so uncommon that you won’t see it. You will, and you need to know how to diagnose it and be comfortable about the diagnosis. Be aggressive in your therapy, even in patients who are asymptomatic. Follow their fibrosis scores, and don’t forget these extrahepatic manifestations, which are more prominent than any of the others in liver disease: osteoporosis, hyperlipidemia, pruritis. Become comfortable with it, understand it, and follow the patients aggressively because you’ll help them.

Steve summed it up well. Disease awareness is a big deal in PBC. Although this is a rare disease, it’s not something you’ll see once in your lifetime or never see. It’s important for practitioners to be aware that this disease exists and recognize that it’s an exciting time for patients with PBC. We have good therapies already in existence but even more exciting therapies in development.

I agree with what everyone said. But let’s not let these patients languish in our clinics. Let’s follow that alkaline phosphatase, and let’s get that alkaline phosphatase to normal.

Having the last name Victor puts me at the end of this. Our panelists have hit on all the issues. To the providers and practitioners watching this, go through your clinic and make sure you’ve optimized the patients you have to make sure they don’t see me for transplant.

That’s very well summed up. Thank you again. To our viewing audience, I hope this 

 discussion was useful and informative. If you enjoyed the content, please subscribe to our e-newsletters to receive 

Experts in hepatology review the unmet needs in primary biliary cholangitis, commenting on liver transplant, ethnic disparities, management of pruritis, as well as other symptoms.

Unmet Needs in the Treatment of PBC

David Victor III, MD

Jennifer B. Green, MD: Implementation of Evidence-Based Therapies for T2D

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

, Jennifer B. Green, MD, an endocrinologist and a clinical trialist at Duke University Medical Center, provided updated insight into the implementation of evidence-based therapies for high-risk patients with 

Green highlighted the success of the COORDINATE-Diabetes trial, which aimed to improve the adoption of essential therapies—high-intensity statins, ACE/ARB inhibitors, and sodium-glucose co-transporter 2 (SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists—in cardiology clinics for patients with T2D and established atherosclerotic cardiovascular disease (ASCVD). The trial showed significant improvements in treatment adherence, addressing a critical gap where only 3-4% of patients were initially receiving all recommended therapies. Green also emphasized the importance of continuing medical education, noting that conferences like these help clinicians stay updated on evolving management strategies, particularly for managing cardio-renal complications in diabetes.

Reflecting on advancements in 2024, Green pointed to the expanding benefits of therapies like GLP-1 receptor agonists and SGLT2 inhibitors, which, beyond managing glucose and weight, are now shown to provide substantial cardiovascular and kidney-related outcomes. She expressed satisfaction in knowing that her prescribing practices are delivering broader benefits than initially expected, reinforcing the importance of implementing the latest evidence to improve patient outcomes.

Disclosures: Relevant disclosures for Green include Bayer, Boehringer Ingelheim, Eli Lilly, Merck, and others.

Green JB. From Research to Guidelines to Implementing Good Clinical Practice in the Management of Diabetes. Presented at the 22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC). Los Angeles, California. December 12-14, 2024.

Dr. Jennifer B. Green discussed the implementation of evidence-based therapies for high-risk type 2 diabetes patients at the WCIRDC. She highlighted the COORDINATE-Diabetes trial's success in improving adherence to essential therapies in cardiology clinics, addressing a significant treatment gap. Green emphasized the role of continuing medical education in updating clinicians on management strategies, particularly for cardio-renal complications. She noted the expanding benefits of GLP-1 receptor agonists and SGLT2 inhibitors, which now show substantial cardiovascular and kidney-related outcomes, underscoring the importance of applying the latest evidence in practice.

Jennifer B. Green, MD highlights the successful implementation of evidence-based therapies for high-risk patients with type 2 diabetes.

Jennifer B. Green, MD

Jennifer Goldman, RPh, PharmD, CDCES, BC-ADM, FCCP

The burden of respiratory viral diseases is greater than the approximate 6.6 million deaths and 633 million infections globally due to COVID-19. The U.S. has recently experienced an influenza epidemic,

 and high respiratory syncytial virus (RSV) case rates.

With a high number of students and staff together in close quarters, school children are extremely susceptible to not only getting a respiratory infection, but also to passing it on to others. School health personnel are important advocates for reducing viral transmission in classrooms.

Our preliminary data from the COVID-19 pandemic show that school health personnel lack support to implement intervention guidance during outbreaks, and classrooms struggle to implement broad guidance due to instructional challenges.

 Quantitative microbial risk assessments (QMRA)

 can be used to address this gap in school health resources and further provide school personnel with necessary decision making tools.

QMRAs involve the use of information such as mathematical representations of pathogens spread, pathogen dose-response relationships, and human behaviors in specific situations to estimate a probability of a negative health outcome, usually infection, given a specific exposure level. These QMRA models can serve as fast and inexpensive decision-making tools during outbreaks or future pandemics. However, these risk assessment models tend to be in the form of mathematical equations or computational code which are difficult for the lay person to use. However, there are recent efforts in the field of QMRA

 to put these models in the form of applications or user-friendly tools to increase accessibility to decision-makers.

Our American Lung Association Catalyst Award will serve 3-fold:

Develop risk assessment models to estimate respiratory viral infection risk reductions for bundled interventions in elementary school environments.

Create and pilot a risk decision tool for school health personnel for informing intervention strategies.

Evaluate a range of plausible intervention effect sizes to support the development of the risk calculator tool for a future intervention study.

We have developed a prototype QMRA risk calculator tool that allows users to explore hypothetical classroom scenarios to estimate risk of infection per student. User inputs include number of students, student grade-level, activity level of students, room size, fresh air exchange rate, percent of students assumed to be infected, pathogen of interest (i.e., rhinovirus, influenza A virus, SARS-CoV-2), and more.

We recently distributed an online survey to school administrators, teachers, school health staff and facilities mangers at three public school districts, 3 private schools, and the Arizona Department of Education’s Arizona School Nurse Access Program (ASAP). This survey will gather information about strategies and barriers to implementing interventions for reducing transmission during flu season or respiratory viral outbreaks.

Data from the survey will be used to iteratively improve our risk assessment tool’s user inputs and to create some hypothetical case scenarios (e.g., rhinovirus infections among 5% of the class that spent 1 hour in a small music classroom with poor fresh air circulation) using the tool to predict how single and bundled interventions can reduce average individual student infection risks for given cases.

We are also soliciting feedback on the design, usability, and interpretability of our prototype tool. In June 2024, we presented the prototype tool at a workshop as part of the National Association for School Nurses Conference 2024. Attendees provided feedback on tool input options and brainstormed on potential uses of risk-based tools to support school health. Results are being analyzed, and we are scheduling focus groups with Arizona-based school districts to gain further feedback on the prototype tool. Other future efforts include measuring the tool’s ability to inform decision-making for school personnel. This will be done using a survey of 80 school health personnel before and after use of the tool.

Developing risk decision tools for school health personnel to reduce respiratory infection transmission will protect asthmatic children’s health and offer schools needed public health support. The generated data will support future research that expands this work to include 1) schools across other grade levels and from other geographic regions, 2) evaluation of household contributions to infection risks, 3) evaluation of tool effectiveness.

Wilson has worked on previous projects funded by companies that make air and surface hygiene products, including SC Johnson, Reckitt, and Ecolab.

Prater E. The U.S. is officially in a flu epidemic, federal health officials say. They’re preparing to deploy troops and ventilators if necessary. 

. https://fortune.com/well/2022/11/04/us-united-states-in-flu-epidemic-federal-health-officials-say-cdc-hhs-rsv-covid-omicron-2022/. Published November 4, 2022. Accessed November 9, 2022.

McPhillips D. RSV hospitalizations shoot up to levels typically seen in December, CDC data shows. 

. https://www.cnn.com/2022/11/03/health/rsv-hospitalizations-high-levels. Published November 3, 2022. Accessed November 9, 2022.

Centers for Disease Control and Prevention. Asthma in Children. Published online June 27, 2019. Accessed November 9, 2022. https://www.cdc.gov/healthyschools/bam/diseases/asthma-in-children.htm

Wilson AM, Ogunseye OO, DiGioia O, Gerald LB, Lowe AA. Barriers to COVID-19 Intervention Implementation in K-5 Classrooms: A Survey of Teachers from a District with Mask Mandates despite a Statewide Mask Mandate Ban. 

. 2022;19(14):8311. doi:10.3390/ijerph19148311

Lowe AA, Ravi P, Gerald LB, Wilson AM. The Changing Job of School Nurses during the COVID-19 Pandemic: A Media Content Analysis of Contributions to Stress. 

. Published online September 16, 2022:wxac053. doi:10.1093/annweh/wxac053

Wilson AM, Ravi P, Pargas NT, Gerald LB, Lowe AA. School health systems under strain: an example of COVID-19 experiences & burnout among school health staff in Pima County, Arizona. 

. 2023;23(1):1626. doi:10.1186/s12889-023-16532-8

Quantitative Microbial Risk Assessment: Second Edition

Gerrity D, Crank K, Steinle‐Darling E, Pecson BM. Establishing pathogen log reduction value targets for direct potable reuse in the United States. 

Gerrity D, Kaufman A, Pecson B, Seto E, Olivieri A. DPRisk. Published online 2019. https://edmundseto.shinyapps.io/QMRAv100/

Heida A, Maal-Bared R, Veillette M, et al. Quantitative microbial risk assessment (QMRA) tool for modelling pathogen infection risk to wastewater treatment plant workers. 

. Published online May 2024:121858. doi:10.1016/j.watres.2024.121858

Wilson AM, Canter K, Abney SE, et al. An application for relating

 shower water monitoring results to estimated health outcomes. 

. 2022;221:118812. doi:10.1016/j.watres.2022.118812

Sepucha KR, Borkhoff CM, Lally J, et al. Establishing the effectiveness of patient decision aids: key constructs and measurement instruments. 

. 2013;13(S2):S12. doi:10.1186/1472-6947-13-S2-S12

Wilson details how her team plans to develop risk assessment models to estimate respiratory viral infection risk reductions for interventions in elementary schools.

Helping Schools Calculate Respiratory Infection Risk

Lynn B. Gerald, PhD, MSPH

Anti-VEGF for RVO: The Gold Standard

I'm sorry, it seems there is no article provided for me to summarize and extract key takeaways from. Could you please provide the text of the article

John W Kitchens, MD, bookends the discussion by highlighting the landscape of branch vein occlusion (BRVO) treatment options. 

Anti-VEGF for RVO: The Gold Standard 

Margaret A Chang, MD, MS  

 I’d love for you to share with the viewers what strategies you have implemented based on your experiences to educate patients about their journey. Because that’s so important, as John has said, about making this a patient-centered diagnosis. What’s a day in the life of Dr Maron and Dr Ommen in how you approach these issues?

 I’ll go first. Like I’m sure Steve does, we spend a lot of time with patients when they come and do our own education with them, along with our health care team and nurse practitioners to educate patients about the disease. We spend a lot of time on education, reassurance, putting these issues that we’ve talked about in perspective, and doing a lot of shared decision-making, going through treatment options. At the end of the day, we try to deliver the message that hypertrophic cardiomyopathy [HCM] is a highly treatable disease. It’s going to probably be more so in the future, but even today it’s very treatable and a disease that’s compatible with normal life expectancy and good quality of life for the vast majority of patients. That’s the messaging that we give to patients the best that we can.

 I’d echo the same thing. Patients come to us after having done their own education attempts on the internet, freaked out with wide eyes because they’ve read all the dramatic stories that are available, and we have to remind them that people who have normal lives don’t usually blog about it.

I’d like to reiterate the same words about HCM in the modern era. We’ve gone from an era where it was 100% fatal in 1958 when Donald Teare described it to a 6% annual mortality in the 1980s to an annual mortality that’s the same as the general population. It’s a highly treatable disease for most patients. There are patients in whom there are issues. This discussion wasn’t about sudden cardiac arrest, which would be another 2 hours. Then there are quality-of-life issues that some patients have. But it’s a highly treatable disease and we’re getting more tools in our toolbox for the future, which is exciting.

 That’s super. Javed, any final thoughts you want to share?

 My final thought is that we have these therapies and we want to do anything and everything that we can for the patients to not unnecessarily suffer. The question is how do we educate the clinical community at large to refer the patients to the appropriate centers and to diagnose and screen these patients? While the specialists are very interested in and have a lot of these tools, more mass education about this disease would also be needed.

 From an administrator’s point of view, let me ask you to put that hat on for a second. When you’re looking at making recommendations for clinicians who are interested in getting involved in this, what things would you say are needed in terms of understanding things like catheter-based approaches, surgical approaches, and volume, which you talked a bit about? What do you think about setting certain expectations?

 You can modify behavior quite a lot by creating appropriate incentive structures in terms of education, screening, and quality metrics. You can also set up tools. We live in this digital age and everybody is on an electronic health record. A lot of the education and best practice advisories can be had for our patients in this era. Education and reminder systems are easier in the current day and age.

 Super. John, I’m going to turn to you last. You always keep the patient in the center. I’m curious to hear your final thoughts.

 First, I’m humbled by the expertise at this panel and not being an HCM expert. I feel a tremendous need to think about the infrastructure for elevating the quality of care throughout the nation. What does that entail? Does it entail thinking about algorithms, building shared decision-making tools, integrating routine assessments of health status with the KCCQ [Kansas City Cardiomyopathy Questionnaire], and coming up with very practical management strategies so that you don’t have to be in Boston or Rochester, Minnesota, to get high-quality care?

 Or Kansas City. That’s what I’m left with. It’s a complicated disease, but it’s an exciting disease. As more treatment options become available, there’s a greater call for thinking about the infrastructure of delivering high-quality patient-centered care. That’s what I’d like to see us move toward so that we can all benefit from the advances being made.

 Super. That’s a great way to conclude. I want to thank all of you for this rich and informative discussion. I want to thank you, our viewers, for watching this 

. If you enjoyed the content, please subscribe for our e-newsletters to receive upcoming 

 and other great content right in your inbox. I’m Jim Januzzi from the Massachusetts General Hospital. Thanks very much for joining.

Expert cardiologists share strategies for educating patients on the treatment and management of hypertrophic cardiomyopathy. 

Patient Education of HCM

Martin S. Maron, MD

Rakesh, how about other emerging studies in both pediatric and adult ADHD [attention-deficit/hyperactivity disorder] treatments? What are you most excited about?

 The world of adult ADHD researchers and clinicians has been more empowered in the last decade or so. If our excitement is being shared by our colleagues listening to us, that’s great, but be ready for even more. In fact, 3 of us—Dr Andrew Cutler, Dr Mattingly, and myself—published a paper in 

 in 2020. I encourage people to check it out. The title of that very paper is “Current and Future Nonstimulants in the Treatment of ADHD.” There are a number of them. Obviously, viloxazine is 1 we have our eyes on. Centanafadine is another compound that shows great promise, with a very different mechanism of action. There are a number of other molecules in development. Our goal is to be very excited, but let’s not forget that what we have today is pretty powerful. We should focus on our accurate identification, matching the patient with the right treatment option, and using measurement-based tools. We remain very excited for what the future holds for us.

 I would add, as David also said, there are other stimulants in development. A variety of nonstimulants are in development. The 1 that’s probably going to get approval soon is viloxazine, but there are others in development. There’s a whole group of digital therapeutics in development. In these digital therapeutics, we use the world around us—digital video games, cognitive enhancers—to strengthen pathways in the brain of adults with ADHD. I have 3 trials going on of digital interventions for adults with ADHD. That’s a really promising and interesting area of the future.

Thanks to all of you for this very rich and informative discussion with my friends. Before we conclude, I’d like to get final thoughts from each of you. Are there any messages you’d like to send to our audience? I also want to thank them for caring about ADHD patients and being with us. Dr Mattingly?

 Thank you, everybody, for joining us. Thank you for the discussion. Most important, ADHD is there. We all see it. When you treat it, you make a big difference. These are the patients who walk in and they’re thankful. They’ll tell you the difference you’ve made in their job, in their family, in their marriage, at their school. Treatment makes a difference. It’s rewarding. Once you get used to this, you’ll be thankful that you dove into this field.

 I echo everything that everyone has said. What’s most important and unique about ADHD is that if you treat depression, you bring the person back to where they were. When you treat anxiety disorder, you bring them back to where they were. When you treat ADHD, you transform this person’s psychological state into a state of mind they’ve never experienced. This is an inflexion point on the trajectory of the success of their life. That’s what is unique about treating ADHD compared with some of the other psychiatric disorders.

 I’ll reflect similarly. It can be such a bittersweet story when they come in and haven’t had treatment or have been only partially treated. We watch them gain confidence and self-esteem and flourish in so many aspects of their lives. It’s rewarding for them and for me. I’ll echo what my colleagues said. Thank you all for having me.

 Here is a good way to look at it. It’s the best of times, and it’s the best of times. There’s nothing negative to talk about in terms of adult ADHD. We have so many treatment options. We have so many pathways we can take to help these individuals. I want to thank our colleagues who are listening. In many ways, you could choose to ignore adult ADHD. You might say, “I’m busy enough. I’ve got so many other disorders to take care.” But let me share this with you. If you’ve identified and treated an adult with ADHD, the transformative power of clinical intervention is 1 of the greatest I’ve seen in my 32-year career in medicine, so I encourage you to be empowered in identifying and treating as optimally as you possibly can. It’s getting more possible with the passage of time. Before I wrap up. Teresa, I want to hear your thoughts. What are you most excited about in the world of ADHD?

First, thank you all for being part of this panel. It’s much appreciated. Thank you to our viewing audience for participating. I want to emphasize that, as all of you have said, there’s so much to look forward to in this field. When I started as an ADHD specialist 20 years ago, we had very few options for treatment. We had very little understanding that there even was adult ADHD. I’ve been thrilled to be part of the process and the evolution in our understanding. I’m very excited to know that there’s much more to come.

 discussion to be useful and informative. We look forward to seeing you in the future. Thank you, everyone.

Drs Rakesh Jain, Greg Mattingly, David W. Goodman, Birgit H. Amann, and Theresa R. Cerulli, discuss emerging agents in the pipeline for the management of pediatric and adult ADHD.

Novel Agents for the Management of Pediatric and Adult ADHD

Rakesh Jain, MD, MPH

Esophageal foreign body impaction (EFBI) occurs in approximately 13 per 100,000 patients admitted to the emergency room, with the most commonly implicated food being steak. Multiple medications have been evaluated to help resolve EFBI based on their mechanisms of action, including nifedipine, sublingual nitroglycerin, proteolytic enzymes, benzodiazepines, and glucagon.

The mechanism of action for glucagon involves decreasing the lower esophageal sphincter tone through smooth muscle relaxation, increasing peristalsis, and improving transit time, all with a ceiling dose effect at 1 mg. Because of this, glucagon has commonly been used in clinical practice to help with food impactions, sometimes with delay in endoscopic intervention to give the medication time to take effect.

A Cochrane Library meta-analysis was completed in 2020 to review conservative management of esophageal soft food bolus impaction, with a single article meeting inclusion criteria for history of acute soft food bolus ingestion, history suggestive of esophageal impaction, and incidence of disimpaction without the need for endoscopic intervention as well as exclusion criteria of sharp- or solid-object ingestion, such as bone or foreign objects like dentures or coins.

The study that met these criteria was a presumed double-blind, parallel-group, randomized controlled trial (RCT) conducted in 1995 by Tibbling et al. in Sweden involving 43 participants and looking at the effects of disimpaction in a placebo versus a diazepam and glucagon group. The study found no significant difference between the groups. Of note, the randomization, baseline patient characteristics, and dropout rates were not described, and it was not clear if the study was evaluated with intention to treat (ITT) versus per protocol (PP) analysis.

With the above study being the only presumed RCT involving glucagon for food disimpaction, the field was in need of further evaluation, especially given the extent of the clinical use of glucagon. In January 2024, de Benito Sanz et al. published a double-blind, multicenter RCT comparing glucagon to placebo in the resolution of alimentary esophageal impaction.

The study was conducted at 4 centers from April 2020 to March 2023 and included patients ≥ 18 years of age with a clinical diagnosis of EFBI, profuse salivation, or oral intolerance after their last meal. Exclusion criteria included pregnancy, non-alimentary foreign body, administration of glucagon or carbonated drinks prior to randomization, known non-passable strictures during prior endoscopy, or manometrically diagnosed esophageal motility disorders.

When patients presented to the ER with the above, the ER provider had a joint assessment with the on-call endoscopist. Although the ER provider and ER staff were not masked, the endoscopist was. The 2 arms of the study involved a placebo IV saline versus 1mg IV glucagon and a mandatory gastroscopy within 30-120 minutes of glucagon administration regardless of clinical symptom resolution. This was followed by a follow-up phone call within 7-10 days for assessment of pain (scale from 0-10) and dysphagia graded in 4 categories (to nothing, solids, liquids, or aphagia). Each arm of the study included 70 patients for 80% power given the success rate of 35% of glucagon based on minimal studies as previously mentioned.

The primary endpoint was the proportion of resolved EFBI while secondary endpoints included the duration of endoscopic exam and extraction length with post hoc analysis of different esophageal diagnoses. Statistical analysis of the primary outcome was done using Z-test and both ITT and PP, and the secondary endpoints were analyzed with chi-squared analysis.

A total of 17 endoscopists were involved in this study with 72 patients in the intervention group and 68 in the placebo. Baseline characteristics were generally similar between the groups except for a greater incidence of known Schatzki rings in the placebo group (

 = .03). EFBI resolved with glucagon in 23.6% (n = 17) of cases versus 20.6% (n = 14) of cases in the placebo group with ITT. In PP analysis, these numbers were 20.9% for the glucagon group and 21.5% in the placebo group.

Secondary endpoints for time required to resolve EFBI were about the same in the 2 groups, but the duration of upper endoscopy was slightly longer in the glucagon group by 1.5 minutes. Post hoc analysis of the benefit of glucagon depending on esophageal diagnoses did not show significance, but it is important to note that the n values were relatively small for these subgroups.

There was no significant difference in the predominant location of the EFBI (lower third of the esophagus), type of EFBI (beef and chicken), and successful removal maneuver (pulsion, roth net, polypectomy snare, foreign body forceps). Across both groups, 8 adverse events were described, including oropharyngeal discomfort, esophageal obstruction, urinary retention, salivary gland infection, COVID, and fever, with the most significant being a case of aspiration pneumonia in the control group in a 92-year-old patient.

The study has clear strengths in that it was a double-blind, multi-center RCT with multiple endoscopists and a short time to EGD. The study did not limit the type of endoscopic interventions, correlating with clinical practice. The secondary outcomes were also very reasonable as a benefit in endoscopic time independent of the primary outcome could have been supportive of the use of glucagon. However, given the thoroughness of this study and its results, glucagon does not seem to make a difference in EFBI resolution, time of endoscopy, or extraction length.

Future studies powered for the subgroup analysis of different esophageal diseases would be interesting to see for specific esophageal diseases and pathophysiologies that might have a greater response to glucagon.

Hardman J, Sharma N, Smith J, Nankivell P. Conservative management of oesophageal soft food bolus impaction. Cochrane Database of Systematic Reviews 2020, Issue 5. Art. No.: CD007352. doi:10.1002/14651858.CD007352.pub3.

de Benito Sanz M, Tejedor-Tejada J, Mangas-Sanjuan C, et al. on behalf of the GLUCAGON study group. Double-Blind Multicenter Randomized Clinical Trial Comparing Glucagon vs Placebo in the Resolution of Alimentary Esophageal Impaction. The American Journal of Gastroenterology 119(1):p 87-96, January 2024. doi:10.14309/ajg.0000000000002511

Findings from a recent randomized controlled trial suggest glucagon does not improve EFBI resolution, time of endoscopy, or extraction length.

Authors