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Targeted Osteoporosis Program May Benefit At-Risk Older Men
Efforts to identify older men at risk for osteoporosis and treat those who are eligible received a boost from results reported from a Veterans Affairs (VA) study that showed a significant increase in screening, treatment, and medication adherence.
The cluster randomized trial used a centralized nurse-led intervention to assess men for traditional osteoporosis risk factors, offer bone density testing, and recommend treatment for eligible men. Over 2 years, the intervention group had a higher average femoral neck bone density than patients who underwent usual care.
“We designed this study to see if a risk factor-based approach, which is what most of the guidelines use, made sense and was feasible — that men would be accepting of screening and [the approach] would yield a similar proportion of people who need osteoporosis treatment as screening in women, which is widely recommended and implemented. And sure enough, we found that about 85% of the men in the VA primary care practices in our target age range of between 65 and 85 actually met criteria for screening, and over half of them had low bone mass. They were very accepting of screening, very accepting of treatment, and had excellent compliance rates. So, our study, we believe, supports the idea of identifying men with at least one risk factor for fracture and offering them osteoporosis screening starting at age 65, similar to what we do for women,” Cathleen S. Colón-Emeric, MD, MHS, said in an interview. She is the lead author of the study, a physician in the Durham VA Health Care System, and professor of medicine at Duke University School of Medicine, Durham, North Carolina.
“We were able to see a positive effect on bone density in the bone health group, compared with the usual care group, which suggests that if we followed these folks longer and had enough of them, we would be able to show a fracture reduction benefit,” Colón-Emeric said.
There have been few randomized trials of screening interventions in men, leading to inconsistencies in guidelines, according to the authors of the new study, published online in JAMA Internal Medicine . Both the US Preventive Services Task Force and the Veterans Health Administration National Center for Health Promotion and Disease Prevention consider there to be insufficient evidence to recommend for or against screening in men who have not experienced a fracture. Some professional societies recommend such screening, but there are inconsistencies in the recommended criteria, such as age range or risk factors.
Beyond the age of 50 years, one in five men will experience an osteoporosis-related fracture at some point in their life, according to a 2009 study. Treatment is inexpensive and effective in both men and women, and economic models suggest that screening using dual-energy x-ray absorptiometry (DXA) would be cost-effective. Still, screening is rare among men, with fewer than 10% of men getting screened before having an osteoporosis-related fracture.
“It’s important to screen men at risk for osteoporosis due to the dramatically increased mortality men suffer after a fragility fracture compared with women. Within 1 year of a hip fracture, mortality is as high as 36%. Studies have also shown that osteoporosis in men is undertreated, with only 10%-50% being prescribed antifracture treatment within 1 year of a hip fracture. Most individuals do not regain their prior level of function after a hip fracture,” said Joe C. Huang, MD, who was asked for comment. He is a clinical assistant professor of gerontology and geriatric medicine at Harborview Medical Center Senior Care Clinic and Healthy Bones Clinic in Seattle.
Details of the Intervention
The bone health service (BHS) intervention employed an electronic health record case-finding tool and a nurse care manager who undertook screening and treatment monitoring. They identified potential risk factors that included hyperthyroidism, hyperparathyroidism, rheumatoid arthritis, alcohol dependence, chronic lung disease, chronic liver disease, stroke, parkinsonism, prostate cancer, smoking, diabetes, pernicious anemia, gastrectomy, or high-risk medication use in at least 3 months of the prior 2 years. These medications included traditional antiepileptics, glucocorticoids, and androgen deprivation therapy.
The BHS nurse invited eligible men to be screened using an initial letter, followed by up to three phone calls. After DXA screening, the nurse scheduled an electronic consult with an osteoporosis expert, and patients with a T-score between -1 and -2.4 and an elevated 10-year fracture risk as measured by the Fracture Risk Assessment Tool were recommended for osteoporosis medication, vitamin D, and dietary or supplemental calcium. Following the prescription, the nurse provided patient education over the phone and mailed out written instructions. The nurse also made phone calls at 1 month, 6 months, and 12 months to encourage adherence and address common treatment barriers such as forgetting to take medication or dealing with gastrointestinal effects. The researchers recruited 38 primary care physicians from two VA health systems. The study included 3112 male veterans between the ages of 65 and 85 years (40.4% Black and 56% White). Nearly all participants (85.5%) had at least one indication for screening according to VA undersecretary guidelines, and almost a third (32.1%) had been prescribed androgen deprivation therapy, traditional antiepileptic drugs, or glucocorticoids.
Over a mean follow-up of 1.5 years, there was a much higher screening rate in the BHS group (49.2% vs 2.3%; P < .001), with a similar overall yield of DXA results recommending osteoporosis treatment (22.4% vs 27.2%). In the BHS group, 84.4% of patients who had treatment recommended followed through with treatment initiation. The mean persistence over follow-up was 657 days (SD, 366 days), and adherence was high with a mean proportion of days covered of 91.7%.
It was not possible to statistically compare adherence with the usual-care group because there were too few screened patients found to be eligible for treatment in that group, but the historic mean proportion of days covered at the two participating facilities was 52%.
After 2 years, the mean femoral neck T-score tested randomly in a subset of patients was better in the BHS arm, although it did not meet statistical significance according to the Bonferroni corrected criterion of P < .025 (-0.55 vs -0.70; P = .04). Fracture rates were similar between the two groups (1.8% vs 2.0%; P = .69).
Can the Findings Be Translated Across Clinics?
It remains to be seen how well the model could translate to other healthcare settings, according to Kenny Lin, MD, MPH, who was asked for comment on the study. “Outside of the VA health system and perhaps integrated HMOs [health maintenance organizations] such as Kaiser, Geisinger, etc., it seems unlikely that most primary care docs will have access to a centralized bone health service. Who’s going to pay for it? It leaves unanswered the question of whether it’s more efficient to address [osteoporosis] screening on a practice or population level. I suspect the latter is probably superior, but this study doesn’t provide any empiric evidence that this is so,” said Lin, associate director of the Penn Medicine Lancaster General Hospital’s Family Medicine Residency Program, Lancaster, Pennsylvania. The findings could help sway recommendations to screen men for osteoporosis, according to Susan Ott, MD, who was also asked for comment. Guideline committees “have been trying to be very scientific [about it]. I think they overdo it because they only look at one or two kinds of studies, and there are more kinds of science than just a randomized clinical trial. But they’re kind of stuck on that. The fact that this study was a randomized trial maybe they will finally change their recommendation, because there really shouldn’t be any difference in screening for men and for women. The men are actually discriminated against,” said Ott, emeritus professor of medicine at the University of Washington, Seattle.
In fact, she noted that the risks for men are similar to those for women, except that men tend to develop issues 5-10 years later in life. To screen and treat men, healthcare systems can “do the same thing they do with women. Just change the age range,” Ott said.
Lin sounded a different note, suggesting that the focus should remain on improvement of screening and treatment adherence in women. “We know that up to two thirds of women discontinue osteoporosis drugs within a year, and if we can’t figure out how to improve abysmal adherence in women, it’s unlikely we will persuade enough men to take these drugs to make a difference,” he said.
The study was funded by a grant from the VA Health Systems Research. Colón-Emeric, Lin, Ott, and Huang reported having no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Efforts to identify older men at risk for osteoporosis and treat those who are eligible received a boost from results reported from a Veterans Affairs (VA) study that showed a significant increase in screening, treatment, and medication adherence.
The cluster randomized trial used a centralized nurse-led intervention to assess men for traditional osteoporosis risk factors, offer bone density testing, and recommend treatment for eligible men. Over 2 years, the intervention group had a higher average femoral neck bone density than patients who underwent usual care.
“We designed this study to see if a risk factor-based approach, which is what most of the guidelines use, made sense and was feasible — that men would be accepting of screening and [the approach] would yield a similar proportion of people who need osteoporosis treatment as screening in women, which is widely recommended and implemented. And sure enough, we found that about 85% of the men in the VA primary care practices in our target age range of between 65 and 85 actually met criteria for screening, and over half of them had low bone mass. They were very accepting of screening, very accepting of treatment, and had excellent compliance rates. So, our study, we believe, supports the idea of identifying men with at least one risk factor for fracture and offering them osteoporosis screening starting at age 65, similar to what we do for women,” Cathleen S. Colón-Emeric, MD, MHS, said in an interview. She is the lead author of the study, a physician in the Durham VA Health Care System, and professor of medicine at Duke University School of Medicine, Durham, North Carolina.
“We were able to see a positive effect on bone density in the bone health group, compared with the usual care group, which suggests that if we followed these folks longer and had enough of them, we would be able to show a fracture reduction benefit,” Colón-Emeric said.
There have been few randomized trials of screening interventions in men, leading to inconsistencies in guidelines, according to the authors of the new study, published online in JAMA Internal Medicine . Both the US Preventive Services Task Force and the Veterans Health Administration National Center for Health Promotion and Disease Prevention consider there to be insufficient evidence to recommend for or against screening in men who have not experienced a fracture. Some professional societies recommend such screening, but there are inconsistencies in the recommended criteria, such as age range or risk factors.
Beyond the age of 50 years, one in five men will experience an osteoporosis-related fracture at some point in their life, according to a 2009 study. Treatment is inexpensive and effective in both men and women, and economic models suggest that screening using dual-energy x-ray absorptiometry (DXA) would be cost-effective. Still, screening is rare among men, with fewer than 10% of men getting screened before having an osteoporosis-related fracture.
“It’s important to screen men at risk for osteoporosis due to the dramatically increased mortality men suffer after a fragility fracture compared with women. Within 1 year of a hip fracture, mortality is as high as 36%. Studies have also shown that osteoporosis in men is undertreated, with only 10%-50% being prescribed antifracture treatment within 1 year of a hip fracture. Most individuals do not regain their prior level of function after a hip fracture,” said Joe C. Huang, MD, who was asked for comment. He is a clinical assistant professor of gerontology and geriatric medicine at Harborview Medical Center Senior Care Clinic and Healthy Bones Clinic in Seattle.
Details of the Intervention
The bone health service (BHS) intervention employed an electronic health record case-finding tool and a nurse care manager who undertook screening and treatment monitoring. They identified potential risk factors that included hyperthyroidism, hyperparathyroidism, rheumatoid arthritis, alcohol dependence, chronic lung disease, chronic liver disease, stroke, parkinsonism, prostate cancer, smoking, diabetes, pernicious anemia, gastrectomy, or high-risk medication use in at least 3 months of the prior 2 years. These medications included traditional antiepileptics, glucocorticoids, and androgen deprivation therapy.
The BHS nurse invited eligible men to be screened using an initial letter, followed by up to three phone calls. After DXA screening, the nurse scheduled an electronic consult with an osteoporosis expert, and patients with a T-score between -1 and -2.4 and an elevated 10-year fracture risk as measured by the Fracture Risk Assessment Tool were recommended for osteoporosis medication, vitamin D, and dietary or supplemental calcium. Following the prescription, the nurse provided patient education over the phone and mailed out written instructions. The nurse also made phone calls at 1 month, 6 months, and 12 months to encourage adherence and address common treatment barriers such as forgetting to take medication or dealing with gastrointestinal effects. The researchers recruited 38 primary care physicians from two VA health systems. The study included 3112 male veterans between the ages of 65 and 85 years (40.4% Black and 56% White). Nearly all participants (85.5%) had at least one indication for screening according to VA undersecretary guidelines, and almost a third (32.1%) had been prescribed androgen deprivation therapy, traditional antiepileptic drugs, or glucocorticoids.
Over a mean follow-up of 1.5 years, there was a much higher screening rate in the BHS group (49.2% vs 2.3%; P < .001), with a similar overall yield of DXA results recommending osteoporosis treatment (22.4% vs 27.2%). In the BHS group, 84.4% of patients who had treatment recommended followed through with treatment initiation. The mean persistence over follow-up was 657 days (SD, 366 days), and adherence was high with a mean proportion of days covered of 91.7%.
It was not possible to statistically compare adherence with the usual-care group because there were too few screened patients found to be eligible for treatment in that group, but the historic mean proportion of days covered at the two participating facilities was 52%.
After 2 years, the mean femoral neck T-score tested randomly in a subset of patients was better in the BHS arm, although it did not meet statistical significance according to the Bonferroni corrected criterion of P < .025 (-0.55 vs -0.70; P = .04). Fracture rates were similar between the two groups (1.8% vs 2.0%; P = .69).
Can the Findings Be Translated Across Clinics?
It remains to be seen how well the model could translate to other healthcare settings, according to Kenny Lin, MD, MPH, who was asked for comment on the study. “Outside of the VA health system and perhaps integrated HMOs [health maintenance organizations] such as Kaiser, Geisinger, etc., it seems unlikely that most primary care docs will have access to a centralized bone health service. Who’s going to pay for it? It leaves unanswered the question of whether it’s more efficient to address [osteoporosis] screening on a practice or population level. I suspect the latter is probably superior, but this study doesn’t provide any empiric evidence that this is so,” said Lin, associate director of the Penn Medicine Lancaster General Hospital’s Family Medicine Residency Program, Lancaster, Pennsylvania. The findings could help sway recommendations to screen men for osteoporosis, according to Susan Ott, MD, who was also asked for comment. Guideline committees “have been trying to be very scientific [about it]. I think they overdo it because they only look at one or two kinds of studies, and there are more kinds of science than just a randomized clinical trial. But they’re kind of stuck on that. The fact that this study was a randomized trial maybe they will finally change their recommendation, because there really shouldn’t be any difference in screening for men and for women. The men are actually discriminated against,” said Ott, emeritus professor of medicine at the University of Washington, Seattle.
In fact, she noted that the risks for men are similar to those for women, except that men tend to develop issues 5-10 years later in life. To screen and treat men, healthcare systems can “do the same thing they do with women. Just change the age range,” Ott said.
Lin sounded a different note, suggesting that the focus should remain on improvement of screening and treatment adherence in women. “We know that up to two thirds of women discontinue osteoporosis drugs within a year, and if we can’t figure out how to improve abysmal adherence in women, it’s unlikely we will persuade enough men to take these drugs to make a difference,” he said.
The study was funded by a grant from the VA Health Systems Research. Colón-Emeric, Lin, Ott, and Huang reported having no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Efforts to identify older men at risk for osteoporosis and treat those who are eligible received a boost from results reported from a Veterans Affairs (VA) study that showed a significant increase in screening, treatment, and medication adherence.
The cluster randomized trial used a centralized nurse-led intervention to assess men for traditional osteoporosis risk factors, offer bone density testing, and recommend treatment for eligible men. Over 2 years, the intervention group had a higher average femoral neck bone density than patients who underwent usual care.
“We designed this study to see if a risk factor-based approach, which is what most of the guidelines use, made sense and was feasible — that men would be accepting of screening and [the approach] would yield a similar proportion of people who need osteoporosis treatment as screening in women, which is widely recommended and implemented. And sure enough, we found that about 85% of the men in the VA primary care practices in our target age range of between 65 and 85 actually met criteria for screening, and over half of them had low bone mass. They were very accepting of screening, very accepting of treatment, and had excellent compliance rates. So, our study, we believe, supports the idea of identifying men with at least one risk factor for fracture and offering them osteoporosis screening starting at age 65, similar to what we do for women,” Cathleen S. Colón-Emeric, MD, MHS, said in an interview. She is the lead author of the study, a physician in the Durham VA Health Care System, and professor of medicine at Duke University School of Medicine, Durham, North Carolina.
“We were able to see a positive effect on bone density in the bone health group, compared with the usual care group, which suggests that if we followed these folks longer and had enough of them, we would be able to show a fracture reduction benefit,” Colón-Emeric said.
There have been few randomized trials of screening interventions in men, leading to inconsistencies in guidelines, according to the authors of the new study, published online in JAMA Internal Medicine . Both the US Preventive Services Task Force and the Veterans Health Administration National Center for Health Promotion and Disease Prevention consider there to be insufficient evidence to recommend for or against screening in men who have not experienced a fracture. Some professional societies recommend such screening, but there are inconsistencies in the recommended criteria, such as age range or risk factors.
Beyond the age of 50 years, one in five men will experience an osteoporosis-related fracture at some point in their life, according to a 2009 study. Treatment is inexpensive and effective in both men and women, and economic models suggest that screening using dual-energy x-ray absorptiometry (DXA) would be cost-effective. Still, screening is rare among men, with fewer than 10% of men getting screened before having an osteoporosis-related fracture.
“It’s important to screen men at risk for osteoporosis due to the dramatically increased mortality men suffer after a fragility fracture compared with women. Within 1 year of a hip fracture, mortality is as high as 36%. Studies have also shown that osteoporosis in men is undertreated, with only 10%-50% being prescribed antifracture treatment within 1 year of a hip fracture. Most individuals do not regain their prior level of function after a hip fracture,” said Joe C. Huang, MD, who was asked for comment. He is a clinical assistant professor of gerontology and geriatric medicine at Harborview Medical Center Senior Care Clinic and Healthy Bones Clinic in Seattle.
Details of the Intervention
The bone health service (BHS) intervention employed an electronic health record case-finding tool and a nurse care manager who undertook screening and treatment monitoring. They identified potential risk factors that included hyperthyroidism, hyperparathyroidism, rheumatoid arthritis, alcohol dependence, chronic lung disease, chronic liver disease, stroke, parkinsonism, prostate cancer, smoking, diabetes, pernicious anemia, gastrectomy, or high-risk medication use in at least 3 months of the prior 2 years. These medications included traditional antiepileptics, glucocorticoids, and androgen deprivation therapy.
The BHS nurse invited eligible men to be screened using an initial letter, followed by up to three phone calls. After DXA screening, the nurse scheduled an electronic consult with an osteoporosis expert, and patients with a T-score between -1 and -2.4 and an elevated 10-year fracture risk as measured by the Fracture Risk Assessment Tool were recommended for osteoporosis medication, vitamin D, and dietary or supplemental calcium. Following the prescription, the nurse provided patient education over the phone and mailed out written instructions. The nurse also made phone calls at 1 month, 6 months, and 12 months to encourage adherence and address common treatment barriers such as forgetting to take medication or dealing with gastrointestinal effects. The researchers recruited 38 primary care physicians from two VA health systems. The study included 3112 male veterans between the ages of 65 and 85 years (40.4% Black and 56% White). Nearly all participants (85.5%) had at least one indication for screening according to VA undersecretary guidelines, and almost a third (32.1%) had been prescribed androgen deprivation therapy, traditional antiepileptic drugs, or glucocorticoids.
Over a mean follow-up of 1.5 years, there was a much higher screening rate in the BHS group (49.2% vs 2.3%; P < .001), with a similar overall yield of DXA results recommending osteoporosis treatment (22.4% vs 27.2%). In the BHS group, 84.4% of patients who had treatment recommended followed through with treatment initiation. The mean persistence over follow-up was 657 days (SD, 366 days), and adherence was high with a mean proportion of days covered of 91.7%.
It was not possible to statistically compare adherence with the usual-care group because there were too few screened patients found to be eligible for treatment in that group, but the historic mean proportion of days covered at the two participating facilities was 52%.
After 2 years, the mean femoral neck T-score tested randomly in a subset of patients was better in the BHS arm, although it did not meet statistical significance according to the Bonferroni corrected criterion of P < .025 (-0.55 vs -0.70; P = .04). Fracture rates were similar between the two groups (1.8% vs 2.0%; P = .69).
Can the Findings Be Translated Across Clinics?
It remains to be seen how well the model could translate to other healthcare settings, according to Kenny Lin, MD, MPH, who was asked for comment on the study. “Outside of the VA health system and perhaps integrated HMOs [health maintenance organizations] such as Kaiser, Geisinger, etc., it seems unlikely that most primary care docs will have access to a centralized bone health service. Who’s going to pay for it? It leaves unanswered the question of whether it’s more efficient to address [osteoporosis] screening on a practice or population level. I suspect the latter is probably superior, but this study doesn’t provide any empiric evidence that this is so,” said Lin, associate director of the Penn Medicine Lancaster General Hospital’s Family Medicine Residency Program, Lancaster, Pennsylvania. The findings could help sway recommendations to screen men for osteoporosis, according to Susan Ott, MD, who was also asked for comment. Guideline committees “have been trying to be very scientific [about it]. I think they overdo it because they only look at one or two kinds of studies, and there are more kinds of science than just a randomized clinical trial. But they’re kind of stuck on that. The fact that this study was a randomized trial maybe they will finally change their recommendation, because there really shouldn’t be any difference in screening for men and for women. The men are actually discriminated against,” said Ott, emeritus professor of medicine at the University of Washington, Seattle.
In fact, she noted that the risks for men are similar to those for women, except that men tend to develop issues 5-10 years later in life. To screen and treat men, healthcare systems can “do the same thing they do with women. Just change the age range,” Ott said.
Lin sounded a different note, suggesting that the focus should remain on improvement of screening and treatment adherence in women. “We know that up to two thirds of women discontinue osteoporosis drugs within a year, and if we can’t figure out how to improve abysmal adherence in women, it’s unlikely we will persuade enough men to take these drugs to make a difference,” he said.
The study was funded by a grant from the VA Health Systems Research. Colón-Emeric, Lin, Ott, and Huang reported having no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
MASLD/MASH Global Consensus Recommendations Address Guideline Discordance
These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.
“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”
To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.
Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.
The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”
For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.
Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.
Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.
The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.
Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.
“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.
The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.
The new consensus MASLD recommendations should help reconcile the “important differences” between guidelines from around the world, said Dr. Jaideep Behari, of the the University of Pittsburgh Medical Center.
Behari highlighted several points that may be underappreciated in clinical practice. “While many clinicians associate MASLD with obesity and type 2 diabetes, approximately a fifth of people living with MASLD are lean,” he said. “It may also come as a surprise to non-liver specialists that cardiovascular disease is the most common cause of mortality in patients with MASLD.”
He underscored the consensus recommendation to screen patients with type 2 diabetes, those with obesity and at least one cardiometabolic risk factor, and individuals with persistently elevated liver enzymes.
“Since many patients in the first two groups are mainly seen in primary care or endocrinology practices, physicians in these specialties need to be cognizant of these global consensus recommendations,” Behari said.
Turning to therapeutics, he described resmetirom as “a major milestone in the management of MASLD since it is the first drug approved in the US for treatment of MASH with F2 (moderate) or F3 (advanced) fibrosis.”
He noted that treatment requires careful patient selection and monitoring, including VCTE in the 8–20 kPa range, followed by serial liver injury testing. Efficacy should be assessed at 12 months, he noted, since “resmetirom was found to be effective in approximately a quarter of all treated patients in the pivotal clinical trial.”
“These limitations highlight the gaps in the treatment of MASLD/MASH and the need to continue development of other therapies,” Behari said.
Jaideep Behari, MD, PhD, AGAF, is director of the liver steatosis and metabolic wellness program at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. He reported research grant support from AstraZeneca, Madrigal, and recently completed research grant support from Gilead and Pfizer.
The new consensus MASLD recommendations should help reconcile the “important differences” between guidelines from around the world, said Dr. Jaideep Behari, of the the University of Pittsburgh Medical Center.
Behari highlighted several points that may be underappreciated in clinical practice. “While many clinicians associate MASLD with obesity and type 2 diabetes, approximately a fifth of people living with MASLD are lean,” he said. “It may also come as a surprise to non-liver specialists that cardiovascular disease is the most common cause of mortality in patients with MASLD.”
He underscored the consensus recommendation to screen patients with type 2 diabetes, those with obesity and at least one cardiometabolic risk factor, and individuals with persistently elevated liver enzymes.
“Since many patients in the first two groups are mainly seen in primary care or endocrinology practices, physicians in these specialties need to be cognizant of these global consensus recommendations,” Behari said.
Turning to therapeutics, he described resmetirom as “a major milestone in the management of MASLD since it is the first drug approved in the US for treatment of MASH with F2 (moderate) or F3 (advanced) fibrosis.”
He noted that treatment requires careful patient selection and monitoring, including VCTE in the 8–20 kPa range, followed by serial liver injury testing. Efficacy should be assessed at 12 months, he noted, since “resmetirom was found to be effective in approximately a quarter of all treated patients in the pivotal clinical trial.”
“These limitations highlight the gaps in the treatment of MASLD/MASH and the need to continue development of other therapies,” Behari said.
Jaideep Behari, MD, PhD, AGAF, is director of the liver steatosis and metabolic wellness program at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. He reported research grant support from AstraZeneca, Madrigal, and recently completed research grant support from Gilead and Pfizer.
The new consensus MASLD recommendations should help reconcile the “important differences” between guidelines from around the world, said Dr. Jaideep Behari, of the the University of Pittsburgh Medical Center.
Behari highlighted several points that may be underappreciated in clinical practice. “While many clinicians associate MASLD with obesity and type 2 diabetes, approximately a fifth of people living with MASLD are lean,” he said. “It may also come as a surprise to non-liver specialists that cardiovascular disease is the most common cause of mortality in patients with MASLD.”
He underscored the consensus recommendation to screen patients with type 2 diabetes, those with obesity and at least one cardiometabolic risk factor, and individuals with persistently elevated liver enzymes.
“Since many patients in the first two groups are mainly seen in primary care or endocrinology practices, physicians in these specialties need to be cognizant of these global consensus recommendations,” Behari said.
Turning to therapeutics, he described resmetirom as “a major milestone in the management of MASLD since it is the first drug approved in the US for treatment of MASH with F2 (moderate) or F3 (advanced) fibrosis.”
He noted that treatment requires careful patient selection and monitoring, including VCTE in the 8–20 kPa range, followed by serial liver injury testing. Efficacy should be assessed at 12 months, he noted, since “resmetirom was found to be effective in approximately a quarter of all treated patients in the pivotal clinical trial.”
“These limitations highlight the gaps in the treatment of MASLD/MASH and the need to continue development of other therapies,” Behari said.
Jaideep Behari, MD, PhD, AGAF, is director of the liver steatosis and metabolic wellness program at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. He reported research grant support from AstraZeneca, Madrigal, and recently completed research grant support from Gilead and Pfizer.
These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.
“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”
To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.
Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.
The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”
For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.
Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.
Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.
The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.
Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.
“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.
The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.
These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.
“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”
To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.
Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.
The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”
For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.
Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.
Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.
The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.
Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.
“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.
The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.
FROM GASTROENTEROLOGY
Long-Term Data Support Reduced-Dose Maintenance in EoE
, according to a recent meta-analysis of long-term data.
These findings support keeping patients on long-term maintenance therapy to prevent relapse, lead author Alberto Barchi, MD, of IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues, reported.
“Given the high relapse rate after treatment cessation, despite good initial response after induction, there is need for further information about long-term outcomes of maintenance treatments,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, few studies have focused on long-term effects of EoE therapies.”
In response, Dr. Barchi and colleagues conducted the present systematic review and meta-analysis, which included studies evaluating maintenance therapies for EoE with at least 48 weeks of follow-up. Eligible studies enrolled patients with confirmed EoE who had received an induction regimen and continued therapy long-term. The final dataset comprised 9 randomized controlled trials (RCTs) and 11 observational studies, with long-term outcomes were reported among 1,819 patients.
The primary outcome was histologic success, defined as fewer than 15 or 6 eosinophils per high-power field (HPF). Secondary outcomes included clinical and endoscopic response, treatment adherence, and safety events.
Random-effects meta-analyses were performed, with randomized trials and observational studies analyzed separately. Risk ratios for sustained remission versus placebo or induction therapy were calculated, and heterogeneity was assessed using the I² statistic. Safety outcomes included pooled rates of adverse events, severe adverse events, and treatment discontinuation.
Across 9 randomized controlled trials, swallowed topical corticosteroids (STCs) maintained histologic remission (less than 15 eosinophils/HPF) in 86% of patients, while biologics achieved a rate of 79%. At the stricter threshold of less than 6 eosinophils/HPF, remission rates for STCs and biologics were 59% and 70%, respectively.
Clinical remission rates were lower, at 58% for STCs and 59% for biologics. Endoscopic outcomes were less consistent-ly reported, but most trials showed stable or improved scores during long-term treatment.
In observational cohorts, proton pump inhibitors (PPIs) maintained histologic remission in 64% of patients and clinical remission in 80%. For STCs in the real-world setting, histologic and clinical remission rates were 49% and 51%, respectively.
Stepping down the dose of maintenance therapy—whether conventional or biologic—did not increase relapse risk (RR 1.04; 95% CI, 0.72–1.51). In contrast, treatment withdrawal was clearly associated with higher relapse rates: in pooled analyses, continuing therapy yielded nearly an 8-fold greater likelihood of sustained remission compared with discontinuation (RR 7.87; 95% CI, 4.19–14.77).
Safety signals were favorable. Severe adverse events occurred in 3% of patients in randomized trials and 5% in observational studies, while overall withdrawal rates were 10% and 4%, respectively. The most common adverse events with STCs were oropharyngeal candidiasis and reductions in morning cortisol, while biologics were mainly associated with injection-site reactions, headache, and nasopharyngitis.
“Results suggest that prolonging treatment is efficient in maintaining histologic and clinical remission, with overall drug-related safe profiles both in randomized trials and observational studies,” the investigators concluded, noting that more work is needed to determine if there is an optimal drug for maintenance therapy, and if certain patients can successfully discontinue treatment.
The investigators disclosed relationships with Pfizer, UCB Pharma, AstraZeneca, and others.
, according to a recent meta-analysis of long-term data.
These findings support keeping patients on long-term maintenance therapy to prevent relapse, lead author Alberto Barchi, MD, of IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues, reported.
“Given the high relapse rate after treatment cessation, despite good initial response after induction, there is need for further information about long-term outcomes of maintenance treatments,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, few studies have focused on long-term effects of EoE therapies.”
In response, Dr. Barchi and colleagues conducted the present systematic review and meta-analysis, which included studies evaluating maintenance therapies for EoE with at least 48 weeks of follow-up. Eligible studies enrolled patients with confirmed EoE who had received an induction regimen and continued therapy long-term. The final dataset comprised 9 randomized controlled trials (RCTs) and 11 observational studies, with long-term outcomes were reported among 1,819 patients.
The primary outcome was histologic success, defined as fewer than 15 or 6 eosinophils per high-power field (HPF). Secondary outcomes included clinical and endoscopic response, treatment adherence, and safety events.
Random-effects meta-analyses were performed, with randomized trials and observational studies analyzed separately. Risk ratios for sustained remission versus placebo or induction therapy were calculated, and heterogeneity was assessed using the I² statistic. Safety outcomes included pooled rates of adverse events, severe adverse events, and treatment discontinuation.
Across 9 randomized controlled trials, swallowed topical corticosteroids (STCs) maintained histologic remission (less than 15 eosinophils/HPF) in 86% of patients, while biologics achieved a rate of 79%. At the stricter threshold of less than 6 eosinophils/HPF, remission rates for STCs and biologics were 59% and 70%, respectively.
Clinical remission rates were lower, at 58% for STCs and 59% for biologics. Endoscopic outcomes were less consistent-ly reported, but most trials showed stable or improved scores during long-term treatment.
In observational cohorts, proton pump inhibitors (PPIs) maintained histologic remission in 64% of patients and clinical remission in 80%. For STCs in the real-world setting, histologic and clinical remission rates were 49% and 51%, respectively.
Stepping down the dose of maintenance therapy—whether conventional or biologic—did not increase relapse risk (RR 1.04; 95% CI, 0.72–1.51). In contrast, treatment withdrawal was clearly associated with higher relapse rates: in pooled analyses, continuing therapy yielded nearly an 8-fold greater likelihood of sustained remission compared with discontinuation (RR 7.87; 95% CI, 4.19–14.77).
Safety signals were favorable. Severe adverse events occurred in 3% of patients in randomized trials and 5% in observational studies, while overall withdrawal rates were 10% and 4%, respectively. The most common adverse events with STCs were oropharyngeal candidiasis and reductions in morning cortisol, while biologics were mainly associated with injection-site reactions, headache, and nasopharyngitis.
“Results suggest that prolonging treatment is efficient in maintaining histologic and clinical remission, with overall drug-related safe profiles both in randomized trials and observational studies,” the investigators concluded, noting that more work is needed to determine if there is an optimal drug for maintenance therapy, and if certain patients can successfully discontinue treatment.
The investigators disclosed relationships with Pfizer, UCB Pharma, AstraZeneca, and others.
, according to a recent meta-analysis of long-term data.
These findings support keeping patients on long-term maintenance therapy to prevent relapse, lead author Alberto Barchi, MD, of IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues, reported.
“Given the high relapse rate after treatment cessation, despite good initial response after induction, there is need for further information about long-term outcomes of maintenance treatments,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, few studies have focused on long-term effects of EoE therapies.”
In response, Dr. Barchi and colleagues conducted the present systematic review and meta-analysis, which included studies evaluating maintenance therapies for EoE with at least 48 weeks of follow-up. Eligible studies enrolled patients with confirmed EoE who had received an induction regimen and continued therapy long-term. The final dataset comprised 9 randomized controlled trials (RCTs) and 11 observational studies, with long-term outcomes were reported among 1,819 patients.
The primary outcome was histologic success, defined as fewer than 15 or 6 eosinophils per high-power field (HPF). Secondary outcomes included clinical and endoscopic response, treatment adherence, and safety events.
Random-effects meta-analyses were performed, with randomized trials and observational studies analyzed separately. Risk ratios for sustained remission versus placebo or induction therapy were calculated, and heterogeneity was assessed using the I² statistic. Safety outcomes included pooled rates of adverse events, severe adverse events, and treatment discontinuation.
Across 9 randomized controlled trials, swallowed topical corticosteroids (STCs) maintained histologic remission (less than 15 eosinophils/HPF) in 86% of patients, while biologics achieved a rate of 79%. At the stricter threshold of less than 6 eosinophils/HPF, remission rates for STCs and biologics were 59% and 70%, respectively.
Clinical remission rates were lower, at 58% for STCs and 59% for biologics. Endoscopic outcomes were less consistent-ly reported, but most trials showed stable or improved scores during long-term treatment.
In observational cohorts, proton pump inhibitors (PPIs) maintained histologic remission in 64% of patients and clinical remission in 80%. For STCs in the real-world setting, histologic and clinical remission rates were 49% and 51%, respectively.
Stepping down the dose of maintenance therapy—whether conventional or biologic—did not increase relapse risk (RR 1.04; 95% CI, 0.72–1.51). In contrast, treatment withdrawal was clearly associated with higher relapse rates: in pooled analyses, continuing therapy yielded nearly an 8-fold greater likelihood of sustained remission compared with discontinuation (RR 7.87; 95% CI, 4.19–14.77).
Safety signals were favorable. Severe adverse events occurred in 3% of patients in randomized trials and 5% in observational studies, while overall withdrawal rates were 10% and 4%, respectively. The most common adverse events with STCs were oropharyngeal candidiasis and reductions in morning cortisol, while biologics were mainly associated with injection-site reactions, headache, and nasopharyngitis.
“Results suggest that prolonging treatment is efficient in maintaining histologic and clinical remission, with overall drug-related safe profiles both in randomized trials and observational studies,” the investigators concluded, noting that more work is needed to determine if there is an optimal drug for maintenance therapy, and if certain patients can successfully discontinue treatment.
The investigators disclosed relationships with Pfizer, UCB Pharma, AstraZeneca, and others.
FROM GASTROENTEROLOGY
Simpler Approach Increases Diagnostic Accuracy of Timed Barium Esophagram for Achalasia
, according to investigators.
The classification tree offers a practical alternative for evaluating esophagogastric junction (EGJ) outflow disorders when more advanced methods like high-resolution manometry (HRM) or functional lumen imaging probe (FLIP) panometry are unavailable, lead author Ofer Z. Fass, MD, of Northwestern University, Chicago, and colleagues reported.
“[T]here are limited data on normative TBE values,” the investigators wrote in Gastroenterology. “Furthermore, data supporting the accuracy of TBE as a screening test for esophageal motility disorders, as well as clinically relevant test thresholds, remains limited.”
TBE is conventionally interpreted using a handful of single measurements, most often the barium column height at 1, 2, or 5 minutes. Although these metrics are simple to obtain, variability in technique, cutoff values, and interpretation across centers limits reproducibility and weakens diagnostic accuracy, according to the investigators. The role of TBE has therefore been largely confined to adjudicating inconclusive manometry findings, but even in that setting, the absence of validated reference standards constrains its utility as a reliable screening tool.
To address this gap, Fass and colleagues conducted a prospective analysis of 290 patients who underwent TBE at Northwestern Memorial Hospital, Chicago, with HRM and FLIP panometry, interpreted according to the Chicago Classification version 4.0 (CCv4.0), serving as the diagnostic reference standards.
Patients were included if they had both TBE and manometry performed within a short interval, ensuring that the two tests could be meaningfully compared. The study population represented a broad spectrum of esophageal motility presentations, allowing the model to be trained on clinically relevant variation.
Beyond column height, the investigators measured barium height at multiple timepoints, maximal esophageal body width, maximum EGJ diameter, and tablet passage. These variables were incorporated into a recursive partitioning algorithm to build a multimetric classification tree aimed at distinguishing EGJ outflow obstruction from other motility disorders.
The optimal tree incorporated three sequential decision levels. At the top was maximum esophageal body width, followed by EGJ diameter and barium height at the second level, and tablet passage at the third. This stepwise structure allowed the model to refine diagnoses by combining simple, reproducible TBE metrics that are already collected in routine practice.
Among the 290 patients, 121 (42%) had EGJ outflow disorders, 151 (52%) had no outflow disorder, and 18 (6%) had inconclusive manometry findings. Using conventional interpretation with column height and tablet passage, TBE demonstrated a sensitivity of 77.8%, a specificity of 86.0%, and an accuracy of 82.2%. The multimetric classification tree improved diagnostic performance across all parameters, with a sensitivity of 84.2%, a specificity of 92.1%, and an accuracy of 88.3%.
The advantages of multimetric interpretation were most notable in patients with borderline column heights, which single-metric approaches often misclassify, underscoring the value of integrating multiple measurements into a unified model.
“[T]his study demonstrated that TBE can accurately identify achalasia when analyzed using multiple metrics in a classification tree model,” Fass and colleagues wrote. “Future studies should explore the use of TBE metrics and models to identify more specific esophageal motor disorders (such as esophageal spasm and absent contractility), as well as validation in a larger, multicenter cohort.”
Clinical Takeaways
Rishi Naik, MD, of the Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, Nashville, Tennessee, said the study represents a step forward in how clinicians can use a widely accessible esophageal imaging test.
“This study is important in that it has updated the way we use a very common, readily available imaging test and compared it to the current gold standard of HRM and FLIP,” he told GI & Hepatology News. “This provides a practical, standardized framework for clinicians evaluating patients with suspected esophageal motility disorders.”
Naik noted that while HRM and FLIP provide highly detailed information, both carry drawbacks that limit their universal adoption.
“Practically, HRM is a transnasal test that can be cumbersome, and FLIP is performed during a sedated procedure,” he said. “From a comfort and cost perspective, the esophagram outcompetes. What the TBE lacked was adequate sensitivity and specificity when just looking at column height, which is how the authors overcame this by leveraging the comparisons using CCv4.0.”
Implementation, however, requires discipline.
“A timed barium esophagram is a protocol, not a single esophagram,” Naik said. “Without proper measurements, you can’t follow the decision tree.”
Still, he pointed to radiology’s increasing adoption of artificial intelligence (AI) as a promising way forward.
“AI has already transformed radiological reads, and I’m optimistic it will eventually allow us to incorporate not only width, height, and tablet clearance but also 3D [three-dimensional] reconstructions of bolus retention and pressure to enhance predictive modeling,” Naik said.
This study was supported by the Public Health Service.
The investigators disclosed having relationships with Takeda, Phathom Pharmaceuticals, Medtronic, and others. Naik is a consultant for Sanofi/Regeneron, Eli Lilly and Company, and Renexxion.
A version of this article appeared on Medscape.com.
, according to investigators.
The classification tree offers a practical alternative for evaluating esophagogastric junction (EGJ) outflow disorders when more advanced methods like high-resolution manometry (HRM) or functional lumen imaging probe (FLIP) panometry are unavailable, lead author Ofer Z. Fass, MD, of Northwestern University, Chicago, and colleagues reported.
“[T]here are limited data on normative TBE values,” the investigators wrote in Gastroenterology. “Furthermore, data supporting the accuracy of TBE as a screening test for esophageal motility disorders, as well as clinically relevant test thresholds, remains limited.”
TBE is conventionally interpreted using a handful of single measurements, most often the barium column height at 1, 2, or 5 minutes. Although these metrics are simple to obtain, variability in technique, cutoff values, and interpretation across centers limits reproducibility and weakens diagnostic accuracy, according to the investigators. The role of TBE has therefore been largely confined to adjudicating inconclusive manometry findings, but even in that setting, the absence of validated reference standards constrains its utility as a reliable screening tool.
To address this gap, Fass and colleagues conducted a prospective analysis of 290 patients who underwent TBE at Northwestern Memorial Hospital, Chicago, with HRM and FLIP panometry, interpreted according to the Chicago Classification version 4.0 (CCv4.0), serving as the diagnostic reference standards.
Patients were included if they had both TBE and manometry performed within a short interval, ensuring that the two tests could be meaningfully compared. The study population represented a broad spectrum of esophageal motility presentations, allowing the model to be trained on clinically relevant variation.
Beyond column height, the investigators measured barium height at multiple timepoints, maximal esophageal body width, maximum EGJ diameter, and tablet passage. These variables were incorporated into a recursive partitioning algorithm to build a multimetric classification tree aimed at distinguishing EGJ outflow obstruction from other motility disorders.
The optimal tree incorporated three sequential decision levels. At the top was maximum esophageal body width, followed by EGJ diameter and barium height at the second level, and tablet passage at the third. This stepwise structure allowed the model to refine diagnoses by combining simple, reproducible TBE metrics that are already collected in routine practice.
Among the 290 patients, 121 (42%) had EGJ outflow disorders, 151 (52%) had no outflow disorder, and 18 (6%) had inconclusive manometry findings. Using conventional interpretation with column height and tablet passage, TBE demonstrated a sensitivity of 77.8%, a specificity of 86.0%, and an accuracy of 82.2%. The multimetric classification tree improved diagnostic performance across all parameters, with a sensitivity of 84.2%, a specificity of 92.1%, and an accuracy of 88.3%.
The advantages of multimetric interpretation were most notable in patients with borderline column heights, which single-metric approaches often misclassify, underscoring the value of integrating multiple measurements into a unified model.
“[T]his study demonstrated that TBE can accurately identify achalasia when analyzed using multiple metrics in a classification tree model,” Fass and colleagues wrote. “Future studies should explore the use of TBE metrics and models to identify more specific esophageal motor disorders (such as esophageal spasm and absent contractility), as well as validation in a larger, multicenter cohort.”
Clinical Takeaways
Rishi Naik, MD, of the Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, Nashville, Tennessee, said the study represents a step forward in how clinicians can use a widely accessible esophageal imaging test.
“This study is important in that it has updated the way we use a very common, readily available imaging test and compared it to the current gold standard of HRM and FLIP,” he told GI & Hepatology News. “This provides a practical, standardized framework for clinicians evaluating patients with suspected esophageal motility disorders.”
Naik noted that while HRM and FLIP provide highly detailed information, both carry drawbacks that limit their universal adoption.
“Practically, HRM is a transnasal test that can be cumbersome, and FLIP is performed during a sedated procedure,” he said. “From a comfort and cost perspective, the esophagram outcompetes. What the TBE lacked was adequate sensitivity and specificity when just looking at column height, which is how the authors overcame this by leveraging the comparisons using CCv4.0.”
Implementation, however, requires discipline.
“A timed barium esophagram is a protocol, not a single esophagram,” Naik said. “Without proper measurements, you can’t follow the decision tree.”
Still, he pointed to radiology’s increasing adoption of artificial intelligence (AI) as a promising way forward.
“AI has already transformed radiological reads, and I’m optimistic it will eventually allow us to incorporate not only width, height, and tablet clearance but also 3D [three-dimensional] reconstructions of bolus retention and pressure to enhance predictive modeling,” Naik said.
This study was supported by the Public Health Service.
The investigators disclosed having relationships with Takeda, Phathom Pharmaceuticals, Medtronic, and others. Naik is a consultant for Sanofi/Regeneron, Eli Lilly and Company, and Renexxion.
A version of this article appeared on Medscape.com.
, according to investigators.
The classification tree offers a practical alternative for evaluating esophagogastric junction (EGJ) outflow disorders when more advanced methods like high-resolution manometry (HRM) or functional lumen imaging probe (FLIP) panometry are unavailable, lead author Ofer Z. Fass, MD, of Northwestern University, Chicago, and colleagues reported.
“[T]here are limited data on normative TBE values,” the investigators wrote in Gastroenterology. “Furthermore, data supporting the accuracy of TBE as a screening test for esophageal motility disorders, as well as clinically relevant test thresholds, remains limited.”
TBE is conventionally interpreted using a handful of single measurements, most often the barium column height at 1, 2, or 5 minutes. Although these metrics are simple to obtain, variability in technique, cutoff values, and interpretation across centers limits reproducibility and weakens diagnostic accuracy, according to the investigators. The role of TBE has therefore been largely confined to adjudicating inconclusive manometry findings, but even in that setting, the absence of validated reference standards constrains its utility as a reliable screening tool.
To address this gap, Fass and colleagues conducted a prospective analysis of 290 patients who underwent TBE at Northwestern Memorial Hospital, Chicago, with HRM and FLIP panometry, interpreted according to the Chicago Classification version 4.0 (CCv4.0), serving as the diagnostic reference standards.
Patients were included if they had both TBE and manometry performed within a short interval, ensuring that the two tests could be meaningfully compared. The study population represented a broad spectrum of esophageal motility presentations, allowing the model to be trained on clinically relevant variation.
Beyond column height, the investigators measured barium height at multiple timepoints, maximal esophageal body width, maximum EGJ diameter, and tablet passage. These variables were incorporated into a recursive partitioning algorithm to build a multimetric classification tree aimed at distinguishing EGJ outflow obstruction from other motility disorders.
The optimal tree incorporated three sequential decision levels. At the top was maximum esophageal body width, followed by EGJ diameter and barium height at the second level, and tablet passage at the third. This stepwise structure allowed the model to refine diagnoses by combining simple, reproducible TBE metrics that are already collected in routine practice.
Among the 290 patients, 121 (42%) had EGJ outflow disorders, 151 (52%) had no outflow disorder, and 18 (6%) had inconclusive manometry findings. Using conventional interpretation with column height and tablet passage, TBE demonstrated a sensitivity of 77.8%, a specificity of 86.0%, and an accuracy of 82.2%. The multimetric classification tree improved diagnostic performance across all parameters, with a sensitivity of 84.2%, a specificity of 92.1%, and an accuracy of 88.3%.
The advantages of multimetric interpretation were most notable in patients with borderline column heights, which single-metric approaches often misclassify, underscoring the value of integrating multiple measurements into a unified model.
“[T]his study demonstrated that TBE can accurately identify achalasia when analyzed using multiple metrics in a classification tree model,” Fass and colleagues wrote. “Future studies should explore the use of TBE metrics and models to identify more specific esophageal motor disorders (such as esophageal spasm and absent contractility), as well as validation in a larger, multicenter cohort.”
Clinical Takeaways
Rishi Naik, MD, of the Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, Nashville, Tennessee, said the study represents a step forward in how clinicians can use a widely accessible esophageal imaging test.
“This study is important in that it has updated the way we use a very common, readily available imaging test and compared it to the current gold standard of HRM and FLIP,” he told GI & Hepatology News. “This provides a practical, standardized framework for clinicians evaluating patients with suspected esophageal motility disorders.”
Naik noted that while HRM and FLIP provide highly detailed information, both carry drawbacks that limit their universal adoption.
“Practically, HRM is a transnasal test that can be cumbersome, and FLIP is performed during a sedated procedure,” he said. “From a comfort and cost perspective, the esophagram outcompetes. What the TBE lacked was adequate sensitivity and specificity when just looking at column height, which is how the authors overcame this by leveraging the comparisons using CCv4.0.”
Implementation, however, requires discipline.
“A timed barium esophagram is a protocol, not a single esophagram,” Naik said. “Without proper measurements, you can’t follow the decision tree.”
Still, he pointed to radiology’s increasing adoption of artificial intelligence (AI) as a promising way forward.
“AI has already transformed radiological reads, and I’m optimistic it will eventually allow us to incorporate not only width, height, and tablet clearance but also 3D [three-dimensional] reconstructions of bolus retention and pressure to enhance predictive modeling,” Naik said.
This study was supported by the Public Health Service.
The investigators disclosed having relationships with Takeda, Phathom Pharmaceuticals, Medtronic, and others. Naik is a consultant for Sanofi/Regeneron, Eli Lilly and Company, and Renexxion.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY
GLP-1s Increase GERD Risk Over SGLT2 Inhibitors in T2D
in a cohort study of new users.
Risks for GERD were higher overall for each GLP-1 RA type except lixisenatide, and risks for GERD complications were higher in ever-smokers, patients with obesity, and patients with gastric comorbidities.
“The findings were not entirely surprising,” principal author Laurent Azoulay, PhD, of McGill University and Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada, told GI & Hepatology News. “There is a plausible biological mechanism through which GLP-1 RAs could increase the risk of GERD — namely, by delaying gastric emptying, which can lead to symptoms of reflux. Still, it’s always valuable to see whether the clinical data support what we suspect from a physiological standpoint.”
“As with any medication, it’s about balancing benefits and risks — and being proactive when side effects emerge,” he added.
The study was published online in Annals of Internal Medicine.
Duration of Use, Drug Action
Researchers designed an active comparator new-user cohort study emulating a target trial to estimate the effects of GLP-1 RAs compared with SGLT2 inhibitors on the risk for GERD and its complications among patients with T2D.
The study included 24,708 new users of GLP-1 RAs and 89,096 new users of SGLT2 inhibitors. Participants had a mean age of 56 years, and 55% were men. They initiated treatment with the drugs from January 2013 through December 2021, with follow-up through March 2022.
Three-year risk differences (RDs) and risk ratios (RRs) were estimated and weighted using propensity score fine stratification.
Overall, during follow-up, the incidence rate of GERD was 7.9 per 1000 person-years; 138 complications of GERD were observed, with over 90% of them being Barrett’s esophagus.
Over a median follow-up of 3 years, among GLP-1 RA users compared with SGLT2 inhibitor users, the RRs were 1.27 for GERD, with an RD of 0.7 per 100 patients, and 1.55 for complications, with an RD of 0.8 per 1000 patients.
Further analyses found that risks for GERD were higher overall for each GLP-1 RA type except lixisenatide, and risks for GERD complications were higher in ever-smokers, patients with obesity, and those with gastric comorbidities associated with gastric motility. The findings remained robust across sensitivity analyses addressing various types of biases.
The widening incidence curves with duration of use may indicate that mucosal injury and symptom severity correlate with reflux frequency and duration of esophageal acid exposure, the authors suggested.
GERD risk also was higher with long-acting GLP-1 RA use, suggesting that long-acting GLP-1 RAs (liraglutide, exenatide once weekly, dulaglutide, and semaglutide) may have more sustained delaying effects, they noted.
“These potential risks should be weighed against the established clinical benefits of this drug class, particularly in patients at high risk for gastroparesis and GERD,” the authors concluded.
“Given the mechanism through which these drugs may cause GERD, we can reasonably speculate that a similar effect might be observed in individuals without diabetes,” Azoulay added. “That said, a dedicated study would be needed to confirm that.”
Close Monitoring Advised
Caroline Collins, MD, assistant professor at Emory University School of Medicine in Atlanta, agreed with the findings and said the association between GLP-1s and GERD is consistent with what she has observed in her practice.
“I routinely counsel patients about the potential for GERD symptoms as well as other side effects before initiating GLP-1 therapy,” she told GI & Hepatology News. “Several patients on GLP-1s have reported new or worsening reflux symptoms after initiating therapy. Sometimes, we can lower the dose, and the GERD resolves. Other times initiating GERD treatment or discontinuing the medication is appropriate.”
“Patients with T2D are already at increased risk for delayed gastric emptying, which in itself is a contributor to GERD,” said Collins, who was not involved in the study. “Therefore, adding a GLP-1 RA, which further slows gastric motility, may compound this risk. I consider this when assessing which patients are the best candidates for these medications and often monitor more closely in patients with long-standing diabetes and other predisposing factors to GERD.”
Barrett’s esophagus and esophageal cancer generally occur over many years, she noted. “A median follow-up of 3 years may be insufficient to fully assess the long-term risks of serious complications.”
“Chronic cough, a common but often overlooked manifestation of GERD, was not included in the outcome definitions,” she added. Including chronic cough “may have captured a broader picture of reflux-related symptoms.”
The study was funded by a Foundation Scheme grant from the Canadian Institutes of Health Research. Azoulay holds a Distinguished Research Scholar award from the Fonds de recherche du Quebec – Sante and is the recipient of a William Dawson Scholar award from McGill University.
A version of this article appeared on Medscape.com.
in a cohort study of new users.
Risks for GERD were higher overall for each GLP-1 RA type except lixisenatide, and risks for GERD complications were higher in ever-smokers, patients with obesity, and patients with gastric comorbidities.
“The findings were not entirely surprising,” principal author Laurent Azoulay, PhD, of McGill University and Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada, told GI & Hepatology News. “There is a plausible biological mechanism through which GLP-1 RAs could increase the risk of GERD — namely, by delaying gastric emptying, which can lead to symptoms of reflux. Still, it’s always valuable to see whether the clinical data support what we suspect from a physiological standpoint.”
“As with any medication, it’s about balancing benefits and risks — and being proactive when side effects emerge,” he added.
The study was published online in Annals of Internal Medicine.
Duration of Use, Drug Action
Researchers designed an active comparator new-user cohort study emulating a target trial to estimate the effects of GLP-1 RAs compared with SGLT2 inhibitors on the risk for GERD and its complications among patients with T2D.
The study included 24,708 new users of GLP-1 RAs and 89,096 new users of SGLT2 inhibitors. Participants had a mean age of 56 years, and 55% were men. They initiated treatment with the drugs from January 2013 through December 2021, with follow-up through March 2022.
Three-year risk differences (RDs) and risk ratios (RRs) were estimated and weighted using propensity score fine stratification.
Overall, during follow-up, the incidence rate of GERD was 7.9 per 1000 person-years; 138 complications of GERD were observed, with over 90% of them being Barrett’s esophagus.
Over a median follow-up of 3 years, among GLP-1 RA users compared with SGLT2 inhibitor users, the RRs were 1.27 for GERD, with an RD of 0.7 per 100 patients, and 1.55 for complications, with an RD of 0.8 per 1000 patients.
Further analyses found that risks for GERD were higher overall for each GLP-1 RA type except lixisenatide, and risks for GERD complications were higher in ever-smokers, patients with obesity, and those with gastric comorbidities associated with gastric motility. The findings remained robust across sensitivity analyses addressing various types of biases.
The widening incidence curves with duration of use may indicate that mucosal injury and symptom severity correlate with reflux frequency and duration of esophageal acid exposure, the authors suggested.
GERD risk also was higher with long-acting GLP-1 RA use, suggesting that long-acting GLP-1 RAs (liraglutide, exenatide once weekly, dulaglutide, and semaglutide) may have more sustained delaying effects, they noted.
“These potential risks should be weighed against the established clinical benefits of this drug class, particularly in patients at high risk for gastroparesis and GERD,” the authors concluded.
“Given the mechanism through which these drugs may cause GERD, we can reasonably speculate that a similar effect might be observed in individuals without diabetes,” Azoulay added. “That said, a dedicated study would be needed to confirm that.”
Close Monitoring Advised
Caroline Collins, MD, assistant professor at Emory University School of Medicine in Atlanta, agreed with the findings and said the association between GLP-1s and GERD is consistent with what she has observed in her practice.
“I routinely counsel patients about the potential for GERD symptoms as well as other side effects before initiating GLP-1 therapy,” she told GI & Hepatology News. “Several patients on GLP-1s have reported new or worsening reflux symptoms after initiating therapy. Sometimes, we can lower the dose, and the GERD resolves. Other times initiating GERD treatment or discontinuing the medication is appropriate.”
“Patients with T2D are already at increased risk for delayed gastric emptying, which in itself is a contributor to GERD,” said Collins, who was not involved in the study. “Therefore, adding a GLP-1 RA, which further slows gastric motility, may compound this risk. I consider this when assessing which patients are the best candidates for these medications and often monitor more closely in patients with long-standing diabetes and other predisposing factors to GERD.”
Barrett’s esophagus and esophageal cancer generally occur over many years, she noted. “A median follow-up of 3 years may be insufficient to fully assess the long-term risks of serious complications.”
“Chronic cough, a common but often overlooked manifestation of GERD, was not included in the outcome definitions,” she added. Including chronic cough “may have captured a broader picture of reflux-related symptoms.”
The study was funded by a Foundation Scheme grant from the Canadian Institutes of Health Research. Azoulay holds a Distinguished Research Scholar award from the Fonds de recherche du Quebec – Sante and is the recipient of a William Dawson Scholar award from McGill University.
A version of this article appeared on Medscape.com.
in a cohort study of new users.
Risks for GERD were higher overall for each GLP-1 RA type except lixisenatide, and risks for GERD complications were higher in ever-smokers, patients with obesity, and patients with gastric comorbidities.
“The findings were not entirely surprising,” principal author Laurent Azoulay, PhD, of McGill University and Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada, told GI & Hepatology News. “There is a plausible biological mechanism through which GLP-1 RAs could increase the risk of GERD — namely, by delaying gastric emptying, which can lead to symptoms of reflux. Still, it’s always valuable to see whether the clinical data support what we suspect from a physiological standpoint.”
“As with any medication, it’s about balancing benefits and risks — and being proactive when side effects emerge,” he added.
The study was published online in Annals of Internal Medicine.
Duration of Use, Drug Action
Researchers designed an active comparator new-user cohort study emulating a target trial to estimate the effects of GLP-1 RAs compared with SGLT2 inhibitors on the risk for GERD and its complications among patients with T2D.
The study included 24,708 new users of GLP-1 RAs and 89,096 new users of SGLT2 inhibitors. Participants had a mean age of 56 years, and 55% were men. They initiated treatment with the drugs from January 2013 through December 2021, with follow-up through March 2022.
Three-year risk differences (RDs) and risk ratios (RRs) were estimated and weighted using propensity score fine stratification.
Overall, during follow-up, the incidence rate of GERD was 7.9 per 1000 person-years; 138 complications of GERD were observed, with over 90% of them being Barrett’s esophagus.
Over a median follow-up of 3 years, among GLP-1 RA users compared with SGLT2 inhibitor users, the RRs were 1.27 for GERD, with an RD of 0.7 per 100 patients, and 1.55 for complications, with an RD of 0.8 per 1000 patients.
Further analyses found that risks for GERD were higher overall for each GLP-1 RA type except lixisenatide, and risks for GERD complications were higher in ever-smokers, patients with obesity, and those with gastric comorbidities associated with gastric motility. The findings remained robust across sensitivity analyses addressing various types of biases.
The widening incidence curves with duration of use may indicate that mucosal injury and symptom severity correlate with reflux frequency and duration of esophageal acid exposure, the authors suggested.
GERD risk also was higher with long-acting GLP-1 RA use, suggesting that long-acting GLP-1 RAs (liraglutide, exenatide once weekly, dulaglutide, and semaglutide) may have more sustained delaying effects, they noted.
“These potential risks should be weighed against the established clinical benefits of this drug class, particularly in patients at high risk for gastroparesis and GERD,” the authors concluded.
“Given the mechanism through which these drugs may cause GERD, we can reasonably speculate that a similar effect might be observed in individuals without diabetes,” Azoulay added. “That said, a dedicated study would be needed to confirm that.”
Close Monitoring Advised
Caroline Collins, MD, assistant professor at Emory University School of Medicine in Atlanta, agreed with the findings and said the association between GLP-1s and GERD is consistent with what she has observed in her practice.
“I routinely counsel patients about the potential for GERD symptoms as well as other side effects before initiating GLP-1 therapy,” she told GI & Hepatology News. “Several patients on GLP-1s have reported new or worsening reflux symptoms after initiating therapy. Sometimes, we can lower the dose, and the GERD resolves. Other times initiating GERD treatment or discontinuing the medication is appropriate.”
“Patients with T2D are already at increased risk for delayed gastric emptying, which in itself is a contributor to GERD,” said Collins, who was not involved in the study. “Therefore, adding a GLP-1 RA, which further slows gastric motility, may compound this risk. I consider this when assessing which patients are the best candidates for these medications and often monitor more closely in patients with long-standing diabetes and other predisposing factors to GERD.”
Barrett’s esophagus and esophageal cancer generally occur over many years, she noted. “A median follow-up of 3 years may be insufficient to fully assess the long-term risks of serious complications.”
“Chronic cough, a common but often overlooked manifestation of GERD, was not included in the outcome definitions,” she added. Including chronic cough “may have captured a broader picture of reflux-related symptoms.”
The study was funded by a Foundation Scheme grant from the Canadian Institutes of Health Research. Azoulay holds a Distinguished Research Scholar award from the Fonds de recherche du Quebec – Sante and is the recipient of a William Dawson Scholar award from McGill University.
A version of this article appeared on Medscape.com.
Medicolegal Concerns in Contemporary Private GI Practice
The need for gastroenterology (GI) services is on the rise in the US, with growing rates of colonoscopy, earlier-onset colon cancer, and inflammatory bowel disease. This increase is taking place in the context of a changing regulatory landscape.
, and to that end, a recent educational practice management update was published in Clinical Gastroenterology and Hepatology by Erin Smith Aebel, JD, a health law specialist with Trenam Law in Tampa, Florida. Aebel has been a speaker at several national GI conferences and has addressed GI trainees on these issues in medical schools.
“Healthcare regulation continues to evolve and it’s a complicated area,” Aebel told GI & Hepatology News. “Some physician investors in healthcare ventures see the potential profits but are not fully aware of how a physician’s license and livelihood could be affected by noncompliance.”
Aebel has seen some medical business owners and institutions pushing physicians to their limits in order to maximize profits. “They’re failing to allow them the meaningful things that allow for a long-term productive and successful practice that provides great patient care,” she said. “A current issue I’m dealing with is employers’ taking away physicians’ administrative time and not respecting the work that is necessary for the physician to be efficient and provide great care,” she said. “If too many physicians get squeezed in this manner, they will eventually walk away from big employers to something they can better control.”
Aebel noted that private-equity acquisitions of medical practices — a fast-growing US trend — are often targeted at quick profits and quick exits, which can be inconsistent with quality long-term patient care. “A question to be asked by physicians and patients is who is benefiting from this transaction?” she said. “Sometimes retired physicians can see a great benefit in private equity, but newer physicians can get tied up with a strong noncompete agreement. The best deals are ones that try to find wins for all involved, including patients.”
Many independent gastroenterologists focusing on the demands of daily practice are less aware than they should be of the legal and business administration sides. “I often get clients who come to me complaining about their contracts after they’ve signed them. I don’t have leverage to do as much for them,” she admitted.
From a business standpoint, gastroenterologists need to understand where they can negotiate for financial gain and control. These could relate to compensation and bonuses, as well as opportunities to invest in the practice, the practice management company, and possibly real estate or ambulatory surgery centers (ASCs).
Aebel’s overarching messages to gastroenterologists are as follows: “Be aware. Learn basic health law. Read your contracts before you sign them. And invest in good counsel before you sign agreements,” she said. “In addition, GI practitioners need to have a working knowledge of the federal Anti-Kickback Statute and the federal Stark Law and how they could be commonly applied in their practices.”
These are designed to protect government-funded patient care from monetary influence. The False Claims Act is another federal buttress against fraud and abuse, she said.
Update Details
Though not intended to be legal advice, Aebel’s update touches on several important medicolegal areas.
Stark Law on Self-Referrals
Gastroenterologists should be familiar with this federal law, a self-referral civil penalty statute regulating how physicians can pay themselves in practices that provide designated health services covered by federal healthcare programs such as Medicare or Medicaid.
For a Stark penalty to apply, there must be a physician referral to an entity (eg, lab, hospital, nutrition service, physiotherapy or radiotherapy center) in which the physician or a close family member has a financial interest.
Ambulatory Surgery Centers
Another common area vulnerable to federal fraud and abuse regulation is investment in ASCs. “Generally speaking, it is a felony to pay or be paid anything of value for Medicare or Medicaid business referrals,” Aebel wrote. This provision relates to the general restriction of the federal AKB statute.
A gastroenterologist referring Medicare patients to a center where that physician has an investment could technically violate this law because the physician will receive profit distributions from the referral. In addition to constituting a felony with potential jail time, violation of this statute is grounds for substantial civil monetary penalties and/or exclusion from the government coverage program.
Fortunately, Aebel noted, legal safe harbors cover many financial relationships, including investment in an ASC. The financial arrangement is protected from prosecution if it meets five safe harbor requirements, including nondiscriminatory treatment of government-insured patients and physician investment unrelated to a center’s volume or the value of referrals. If even one aspect is not met, that will automatically constitute a crime.
“However, the government will look at facts and circumstances to determine whether there was an intent to pay for a referral,” Aebel wrote.
The safe harbor designates requirements for four types of ASCs: surgeon-owned, single-specialty, multispecialty, and hospital/physician ASCs.
Private-Equity Investment
With mergers and acquisitions of US medical practices and networks by private-equity firms becoming more common, gastroenterologists need to be aware of the legal issues involved in such investment.
Most states abide by corporate practice of medicine doctrines, which prohibit unlicensed people from direct ownership in a medical practice. These doctrines vary by state, but their primary goal is to ensure that medical decisions are made solely based on patient care and not influenced by corporate interests. The aim is to shield the physician-patient relationship from commercial influence.
“Accordingly, this creates additional complicated structures necessary for private-equity investment in gastroenterology practices,” Aebel wrote. Usually, such investors will invest in a management services organization (MSO), which takes much of the practice’s value via management fees. Gastroenterologists may or may not have an opportunity to invest in the practice and the MSO in this scenario.
Under corporate practice of medicine doctrine, physicians must control the clinical aspects of patient care. Therefore, some states may have restrictions on private-equity companies’ control of the use of medical devices, pricing, medical protocols, or other issues of patient care.
“This needs to be considered when reviewing the investment documents and structural documents proposed by private equity companies,” the advisory stated. From a business standpoint, gastroenterologists need to understand where they can negotiate for financial gain and control over their clinical practice. “This could relate to their compensation, bonuses, and investment opportunities in the practice, the practice management company, and possibly real estate or ASCs.”
Offering a gastroenterologist’s perspective on the paper, Camille Thélin, MD, MSc, an associate professor in the Division of Digestive Diseases and Health at the University of South Florida, Tampa, Florida, who also practices privately, said, that “what Erin Aebel reminds us is that the business side of GI can be just as tricky as the clinical side. Ancillary services like capsule studies or office labs fall under strict Stark rules, ASC ownership has Anti-Kickback Law restrictions, and private-equity deals may affect both your paycheck and your autonomy.”
Thélin’s main takeaway advice is that business opportunities can be valuable but carry real legal risks if not structured correctly. “This isn’t just abstract compliance law — it’s about protecting one’s ability to practice medicine, earn fairly, and avoid devastating penalties,” she told GI & Hepatology News. “This article reinforces the need for proactive legal review and careful structuring of business arrangements so physicians can focus on patient care without stumbling into avoidable legal pitfalls. With the right legal structure, ancillaries, ASCs, and private equity can strengthen your GI practice without risking compliance.”
The bottom line, said Aebel, is that gastroenterologists already in private practice or considering entering one must navigate a complex landscape of compliance and regulatory requirements — particularly when providing ancillary services, investing in ASCs, or engaging with private equity.
Understanding the Stark law, the AKB statute, and the intricacies of private-equity investment is essential to mitigate risks and avoid severe penalties, the advisory stressed. By proactively seeking expert legal and business guidance, gastroenterologists can structure their financial and ownership arrangements in a compliant manner, safeguarding their practices while capitalizing on growth opportunities.
This paper listed no external funding. Neither Aebel nor Thélin had any relevant conflicts of interest.
A version of this article appeared on Medscape.com.
The need for gastroenterology (GI) services is on the rise in the US, with growing rates of colonoscopy, earlier-onset colon cancer, and inflammatory bowel disease. This increase is taking place in the context of a changing regulatory landscape.
, and to that end, a recent educational practice management update was published in Clinical Gastroenterology and Hepatology by Erin Smith Aebel, JD, a health law specialist with Trenam Law in Tampa, Florida. Aebel has been a speaker at several national GI conferences and has addressed GI trainees on these issues in medical schools.
“Healthcare regulation continues to evolve and it’s a complicated area,” Aebel told GI & Hepatology News. “Some physician investors in healthcare ventures see the potential profits but are not fully aware of how a physician’s license and livelihood could be affected by noncompliance.”
Aebel has seen some medical business owners and institutions pushing physicians to their limits in order to maximize profits. “They’re failing to allow them the meaningful things that allow for a long-term productive and successful practice that provides great patient care,” she said. “A current issue I’m dealing with is employers’ taking away physicians’ administrative time and not respecting the work that is necessary for the physician to be efficient and provide great care,” she said. “If too many physicians get squeezed in this manner, they will eventually walk away from big employers to something they can better control.”
Aebel noted that private-equity acquisitions of medical practices — a fast-growing US trend — are often targeted at quick profits and quick exits, which can be inconsistent with quality long-term patient care. “A question to be asked by physicians and patients is who is benefiting from this transaction?” she said. “Sometimes retired physicians can see a great benefit in private equity, but newer physicians can get tied up with a strong noncompete agreement. The best deals are ones that try to find wins for all involved, including patients.”
Many independent gastroenterologists focusing on the demands of daily practice are less aware than they should be of the legal and business administration sides. “I often get clients who come to me complaining about their contracts after they’ve signed them. I don’t have leverage to do as much for them,” she admitted.
From a business standpoint, gastroenterologists need to understand where they can negotiate for financial gain and control. These could relate to compensation and bonuses, as well as opportunities to invest in the practice, the practice management company, and possibly real estate or ambulatory surgery centers (ASCs).
Aebel’s overarching messages to gastroenterologists are as follows: “Be aware. Learn basic health law. Read your contracts before you sign them. And invest in good counsel before you sign agreements,” she said. “In addition, GI practitioners need to have a working knowledge of the federal Anti-Kickback Statute and the federal Stark Law and how they could be commonly applied in their practices.”
These are designed to protect government-funded patient care from monetary influence. The False Claims Act is another federal buttress against fraud and abuse, she said.
Update Details
Though not intended to be legal advice, Aebel’s update touches on several important medicolegal areas.
Stark Law on Self-Referrals
Gastroenterologists should be familiar with this federal law, a self-referral civil penalty statute regulating how physicians can pay themselves in practices that provide designated health services covered by federal healthcare programs such as Medicare or Medicaid.
For a Stark penalty to apply, there must be a physician referral to an entity (eg, lab, hospital, nutrition service, physiotherapy or radiotherapy center) in which the physician or a close family member has a financial interest.
Ambulatory Surgery Centers
Another common area vulnerable to federal fraud and abuse regulation is investment in ASCs. “Generally speaking, it is a felony to pay or be paid anything of value for Medicare or Medicaid business referrals,” Aebel wrote. This provision relates to the general restriction of the federal AKB statute.
A gastroenterologist referring Medicare patients to a center where that physician has an investment could technically violate this law because the physician will receive profit distributions from the referral. In addition to constituting a felony with potential jail time, violation of this statute is grounds for substantial civil monetary penalties and/or exclusion from the government coverage program.
Fortunately, Aebel noted, legal safe harbors cover many financial relationships, including investment in an ASC. The financial arrangement is protected from prosecution if it meets five safe harbor requirements, including nondiscriminatory treatment of government-insured patients and physician investment unrelated to a center’s volume or the value of referrals. If even one aspect is not met, that will automatically constitute a crime.
“However, the government will look at facts and circumstances to determine whether there was an intent to pay for a referral,” Aebel wrote.
The safe harbor designates requirements for four types of ASCs: surgeon-owned, single-specialty, multispecialty, and hospital/physician ASCs.
Private-Equity Investment
With mergers and acquisitions of US medical practices and networks by private-equity firms becoming more common, gastroenterologists need to be aware of the legal issues involved in such investment.
Most states abide by corporate practice of medicine doctrines, which prohibit unlicensed people from direct ownership in a medical practice. These doctrines vary by state, but their primary goal is to ensure that medical decisions are made solely based on patient care and not influenced by corporate interests. The aim is to shield the physician-patient relationship from commercial influence.
“Accordingly, this creates additional complicated structures necessary for private-equity investment in gastroenterology practices,” Aebel wrote. Usually, such investors will invest in a management services organization (MSO), which takes much of the practice’s value via management fees. Gastroenterologists may or may not have an opportunity to invest in the practice and the MSO in this scenario.
Under corporate practice of medicine doctrine, physicians must control the clinical aspects of patient care. Therefore, some states may have restrictions on private-equity companies’ control of the use of medical devices, pricing, medical protocols, or other issues of patient care.
“This needs to be considered when reviewing the investment documents and structural documents proposed by private equity companies,” the advisory stated. From a business standpoint, gastroenterologists need to understand where they can negotiate for financial gain and control over their clinical practice. “This could relate to their compensation, bonuses, and investment opportunities in the practice, the practice management company, and possibly real estate or ASCs.”
Offering a gastroenterologist’s perspective on the paper, Camille Thélin, MD, MSc, an associate professor in the Division of Digestive Diseases and Health at the University of South Florida, Tampa, Florida, who also practices privately, said, that “what Erin Aebel reminds us is that the business side of GI can be just as tricky as the clinical side. Ancillary services like capsule studies or office labs fall under strict Stark rules, ASC ownership has Anti-Kickback Law restrictions, and private-equity deals may affect both your paycheck and your autonomy.”
Thélin’s main takeaway advice is that business opportunities can be valuable but carry real legal risks if not structured correctly. “This isn’t just abstract compliance law — it’s about protecting one’s ability to practice medicine, earn fairly, and avoid devastating penalties,” she told GI & Hepatology News. “This article reinforces the need for proactive legal review and careful structuring of business arrangements so physicians can focus on patient care without stumbling into avoidable legal pitfalls. With the right legal structure, ancillaries, ASCs, and private equity can strengthen your GI practice without risking compliance.”
The bottom line, said Aebel, is that gastroenterologists already in private practice or considering entering one must navigate a complex landscape of compliance and regulatory requirements — particularly when providing ancillary services, investing in ASCs, or engaging with private equity.
Understanding the Stark law, the AKB statute, and the intricacies of private-equity investment is essential to mitigate risks and avoid severe penalties, the advisory stressed. By proactively seeking expert legal and business guidance, gastroenterologists can structure their financial and ownership arrangements in a compliant manner, safeguarding their practices while capitalizing on growth opportunities.
This paper listed no external funding. Neither Aebel nor Thélin had any relevant conflicts of interest.
A version of this article appeared on Medscape.com.
The need for gastroenterology (GI) services is on the rise in the US, with growing rates of colonoscopy, earlier-onset colon cancer, and inflammatory bowel disease. This increase is taking place in the context of a changing regulatory landscape.
, and to that end, a recent educational practice management update was published in Clinical Gastroenterology and Hepatology by Erin Smith Aebel, JD, a health law specialist with Trenam Law in Tampa, Florida. Aebel has been a speaker at several national GI conferences and has addressed GI trainees on these issues in medical schools.
“Healthcare regulation continues to evolve and it’s a complicated area,” Aebel told GI & Hepatology News. “Some physician investors in healthcare ventures see the potential profits but are not fully aware of how a physician’s license and livelihood could be affected by noncompliance.”
Aebel has seen some medical business owners and institutions pushing physicians to their limits in order to maximize profits. “They’re failing to allow them the meaningful things that allow for a long-term productive and successful practice that provides great patient care,” she said. “A current issue I’m dealing with is employers’ taking away physicians’ administrative time and not respecting the work that is necessary for the physician to be efficient and provide great care,” she said. “If too many physicians get squeezed in this manner, they will eventually walk away from big employers to something they can better control.”
Aebel noted that private-equity acquisitions of medical practices — a fast-growing US trend — are often targeted at quick profits and quick exits, which can be inconsistent with quality long-term patient care. “A question to be asked by physicians and patients is who is benefiting from this transaction?” she said. “Sometimes retired physicians can see a great benefit in private equity, but newer physicians can get tied up with a strong noncompete agreement. The best deals are ones that try to find wins for all involved, including patients.”
Many independent gastroenterologists focusing on the demands of daily practice are less aware than they should be of the legal and business administration sides. “I often get clients who come to me complaining about their contracts after they’ve signed them. I don’t have leverage to do as much for them,” she admitted.
From a business standpoint, gastroenterologists need to understand where they can negotiate for financial gain and control. These could relate to compensation and bonuses, as well as opportunities to invest in the practice, the practice management company, and possibly real estate or ambulatory surgery centers (ASCs).
Aebel’s overarching messages to gastroenterologists are as follows: “Be aware. Learn basic health law. Read your contracts before you sign them. And invest in good counsel before you sign agreements,” she said. “In addition, GI practitioners need to have a working knowledge of the federal Anti-Kickback Statute and the federal Stark Law and how they could be commonly applied in their practices.”
These are designed to protect government-funded patient care from monetary influence. The False Claims Act is another federal buttress against fraud and abuse, she said.
Update Details
Though not intended to be legal advice, Aebel’s update touches on several important medicolegal areas.
Stark Law on Self-Referrals
Gastroenterologists should be familiar with this federal law, a self-referral civil penalty statute regulating how physicians can pay themselves in practices that provide designated health services covered by federal healthcare programs such as Medicare or Medicaid.
For a Stark penalty to apply, there must be a physician referral to an entity (eg, lab, hospital, nutrition service, physiotherapy or radiotherapy center) in which the physician or a close family member has a financial interest.
Ambulatory Surgery Centers
Another common area vulnerable to federal fraud and abuse regulation is investment in ASCs. “Generally speaking, it is a felony to pay or be paid anything of value for Medicare or Medicaid business referrals,” Aebel wrote. This provision relates to the general restriction of the federal AKB statute.
A gastroenterologist referring Medicare patients to a center where that physician has an investment could technically violate this law because the physician will receive profit distributions from the referral. In addition to constituting a felony with potential jail time, violation of this statute is grounds for substantial civil monetary penalties and/or exclusion from the government coverage program.
Fortunately, Aebel noted, legal safe harbors cover many financial relationships, including investment in an ASC. The financial arrangement is protected from prosecution if it meets five safe harbor requirements, including nondiscriminatory treatment of government-insured patients and physician investment unrelated to a center’s volume or the value of referrals. If even one aspect is not met, that will automatically constitute a crime.
“However, the government will look at facts and circumstances to determine whether there was an intent to pay for a referral,” Aebel wrote.
The safe harbor designates requirements for four types of ASCs: surgeon-owned, single-specialty, multispecialty, and hospital/physician ASCs.
Private-Equity Investment
With mergers and acquisitions of US medical practices and networks by private-equity firms becoming more common, gastroenterologists need to be aware of the legal issues involved in such investment.
Most states abide by corporate practice of medicine doctrines, which prohibit unlicensed people from direct ownership in a medical practice. These doctrines vary by state, but their primary goal is to ensure that medical decisions are made solely based on patient care and not influenced by corporate interests. The aim is to shield the physician-patient relationship from commercial influence.
“Accordingly, this creates additional complicated structures necessary for private-equity investment in gastroenterology practices,” Aebel wrote. Usually, such investors will invest in a management services organization (MSO), which takes much of the practice’s value via management fees. Gastroenterologists may or may not have an opportunity to invest in the practice and the MSO in this scenario.
Under corporate practice of medicine doctrine, physicians must control the clinical aspects of patient care. Therefore, some states may have restrictions on private-equity companies’ control of the use of medical devices, pricing, medical protocols, or other issues of patient care.
“This needs to be considered when reviewing the investment documents and structural documents proposed by private equity companies,” the advisory stated. From a business standpoint, gastroenterologists need to understand where they can negotiate for financial gain and control over their clinical practice. “This could relate to their compensation, bonuses, and investment opportunities in the practice, the practice management company, and possibly real estate or ASCs.”
Offering a gastroenterologist’s perspective on the paper, Camille Thélin, MD, MSc, an associate professor in the Division of Digestive Diseases and Health at the University of South Florida, Tampa, Florida, who also practices privately, said, that “what Erin Aebel reminds us is that the business side of GI can be just as tricky as the clinical side. Ancillary services like capsule studies or office labs fall under strict Stark rules, ASC ownership has Anti-Kickback Law restrictions, and private-equity deals may affect both your paycheck and your autonomy.”
Thélin’s main takeaway advice is that business opportunities can be valuable but carry real legal risks if not structured correctly. “This isn’t just abstract compliance law — it’s about protecting one’s ability to practice medicine, earn fairly, and avoid devastating penalties,” she told GI & Hepatology News. “This article reinforces the need for proactive legal review and careful structuring of business arrangements so physicians can focus on patient care without stumbling into avoidable legal pitfalls. With the right legal structure, ancillaries, ASCs, and private equity can strengthen your GI practice without risking compliance.”
The bottom line, said Aebel, is that gastroenterologists already in private practice or considering entering one must navigate a complex landscape of compliance and regulatory requirements — particularly when providing ancillary services, investing in ASCs, or engaging with private equity.
Understanding the Stark law, the AKB statute, and the intricacies of private-equity investment is essential to mitigate risks and avoid severe penalties, the advisory stressed. By proactively seeking expert legal and business guidance, gastroenterologists can structure their financial and ownership arrangements in a compliant manner, safeguarding their practices while capitalizing on growth opportunities.
This paper listed no external funding. Neither Aebel nor Thélin had any relevant conflicts of interest.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Fecal Transplant Benefits in Primary C Difficile Infection Similar to Vancomycin
, with efficacy that is comparable to the standard treatment of vancomycin, and in some measures, showing even stronger efficacy, new research showed.
“FMT, prepared and administered according to international guidelines, is an effective and safe treatment option for C difficile infections, which should be considered for all patients with the infection,” first author Frederik Emil Juul, MD, PhD, of the Clinical Effectiveness Research Group, University of Oslo, in Oslo, Norway, told GI & Hepatology News.
FMT even showed a numerical superiority to vancomycin, which, though not statistically significant, “indicates that FMT has the potential to change the current practice of antibiotic therapy and may establish FMT as a first-line treatment for primary CDI,” the authors further asserted in the study, published recently in the Annals of Internal Medicine.
In the treatment of antibiotic-associated colitis due to CDI, vancomycin or fidaxomicin are the standard therapies, yet up to 20% of patients experience one or more symptom recurrences following successful initial antibiotic treatment, prompting the need for continued antibiotic regimens, resulting in increased costs and potential adverse events, while contributing to antibiotic resistance.
FMT, designed to restore a normal functional colonic microenvironment with the transfer of a healthy person’s stool, though still somewhat controversial, has gained acceptance and favor in recent years in the treatment of recurrent CDI, however, research has been lacking on its efficacy in the treatment of primary CDI.
With a previous proof-of-concept trial and observational study showing promising results in primary CDI, Juul and colleagues conducted the current randomized, open-label noninferiority trial.
For the multi-center study, 100 adult patients with CDI, defined as C diff toxin in stool and at least three loose stools daily, and no previous CDI within 1 year prior to enrollment, were randomized at 20 hospitals in Norway to receive either FMT, administered as an enema, without antibiotic pretreatment, or oral vancomycin at a dose of 125 mg, four times daily for 10 days.
The patients had a median age of about 70 years; more than 40% of patients had a Charlson Comorbidity Index score of ≥ 4, indicating severe comorbidity, and a third had severe CDI.
With the trial showing favorable results, a data and safety monitoring board recommended stopping the trial for efficacy and noninferiority after about half of the planned enrollment was reached.
The primary endpoint of a clinical cure, defined as firm stools or less than three bowel movements daily and no disease recurrence within 60 days without additional treatment, was observed in 34 of 51 patients who received FMT (66.7%) compared with 30 of 49 of those receiving vancomycin (61.2%; difference, 5.4 percentage points; P for noninferiority < .001).
The results contradict the theory that response to FMT is 25 percentage points lower than response to vancomycin, the authors noted.
The proportion of patients with clinical cure at day 14 was 70.6% in the FMT group and 77.6% in the vancomycin group, and among those patients, two (5.6%) in the FMT group had disease recurrence compared with eight (21.1%) in the vancomycin group between days 15 and 60.
In the FMT group, 11 patients received additional treatment compared with four in the vancomycin group, predominantly oral vancomycin in both groups.
Despite the high rates of severe comorbidity among the patients at baseline, a subgroup analyses showed no significant differences in treatment effects based on factors including sex, age group, Charlson Comorbidity Index score, or CDI severity.
Importantly, there were also no significant differences in adverse events between the groups.
“Our results indicate that it is reasonable to treat patients with primary CDI with FMT and provide antibiotics only to patients with ongoing symptoms or recurrence after FMT,” the authors concluded.
FMT Faces Challenges in the US
FMT specifically consists of direct instillation of fecal matter to the upper gastrointestinal tract, via capsules or duodenal infusion, or the lower gastrointestinal tract via colonoscopy or enema.
While an AGA guideline issued in 2024 endorsed FMT for the prevention of recurrent, refractory, or fulminant CDI in select adults not responding to standard antibiotics, the association underscored important caveats, including a low quality of evidence, and concluded that FMT could not yet be recommended for other gastrointestinal conditions.
The treatment meanwhile has faced an uphill battle in the US. The provision of screened FMT inocula through the nonprofit OpenBiome, previously the country’s largest stool bank, was recently suspended amid FDA policy changes.
And while other commercial-grade biotherapeutic products Rebyota and Vowst, have received FDA approval, cost and insurance coverage can be significant barriers, said Elizabeth Hohmann, MD, of the Infectious Disease Division at Massachusetts General Hospital, Boston, in an editorial published with the study.
“Currently approved options are expensive and are not available to many who might benefit for various reasons, primarily cost,” she said.
Acceptance Higher in Europe
In Europe, and particularly Norway, acceptance of FMT for CDI and other indications has been more favorable, and while regulation of the treatment has varied among European countries, a new regulation to be implemented by the European Union in 2027 will improve standardization of the production, handling, storage, and other factors of FMT, Juul told GI & Hepatology News.
“I believe the new regulations will make the treatment more available to patients, and a standardization of the FMT production will make future trials more comparable and useful across countries,” he said.
Juul said he further expects that “our results will lower the threshold for choosing FMT as treatment in primary infections. I know that Denmark also gives FMT to patients with primary CDI.”
Quality of Life
Hohmann, who has treated many patients with recurrent CDI with FMT, noted that a key factor that should be underscored is how much better patients can feel after the treatment.
“Although there are no quality of life surveys in [the current study], had they been done, I suspect quality of life might have been higher in the FMT group; in my experience, people feel better after microbiome restoration.”
She added that her patients “report feeling much better, and that’s why I keep doing it,” she said. “I’ve had an 80-year-old patient tell me he’s going back to snow shoveling; another saying she can return to yoga classes.”
“When you have had bad gut microbiome dysbiosis that becomes normal, you feel a lot better,” Hohmann said.
In the treatment of primary CDI, however, Hohmann said the prospects, at least in the US, are likely slim.
“I do not believe that we in the United States will see FMT as a primary treatment of C difficile infection anytime soon,” she wrote in the editorial.
Nevertheless, Hohmann asserted that “FMT should remain available, with appropriate sources of carefully screened inocula for care and for further research into the many illnesses and therapies that are influenced by the health of the gut microbiome.”
This study received funding from the South-East Norway Health Trust. Hohmann had no disclosures to report.
A version of this article appeared on Medscape.com.
, with efficacy that is comparable to the standard treatment of vancomycin, and in some measures, showing even stronger efficacy, new research showed.
“FMT, prepared and administered according to international guidelines, is an effective and safe treatment option for C difficile infections, which should be considered for all patients with the infection,” first author Frederik Emil Juul, MD, PhD, of the Clinical Effectiveness Research Group, University of Oslo, in Oslo, Norway, told GI & Hepatology News.
FMT even showed a numerical superiority to vancomycin, which, though not statistically significant, “indicates that FMT has the potential to change the current practice of antibiotic therapy and may establish FMT as a first-line treatment for primary CDI,” the authors further asserted in the study, published recently in the Annals of Internal Medicine.
In the treatment of antibiotic-associated colitis due to CDI, vancomycin or fidaxomicin are the standard therapies, yet up to 20% of patients experience one or more symptom recurrences following successful initial antibiotic treatment, prompting the need for continued antibiotic regimens, resulting in increased costs and potential adverse events, while contributing to antibiotic resistance.
FMT, designed to restore a normal functional colonic microenvironment with the transfer of a healthy person’s stool, though still somewhat controversial, has gained acceptance and favor in recent years in the treatment of recurrent CDI, however, research has been lacking on its efficacy in the treatment of primary CDI.
With a previous proof-of-concept trial and observational study showing promising results in primary CDI, Juul and colleagues conducted the current randomized, open-label noninferiority trial.
For the multi-center study, 100 adult patients with CDI, defined as C diff toxin in stool and at least three loose stools daily, and no previous CDI within 1 year prior to enrollment, were randomized at 20 hospitals in Norway to receive either FMT, administered as an enema, without antibiotic pretreatment, or oral vancomycin at a dose of 125 mg, four times daily for 10 days.
The patients had a median age of about 70 years; more than 40% of patients had a Charlson Comorbidity Index score of ≥ 4, indicating severe comorbidity, and a third had severe CDI.
With the trial showing favorable results, a data and safety monitoring board recommended stopping the trial for efficacy and noninferiority after about half of the planned enrollment was reached.
The primary endpoint of a clinical cure, defined as firm stools or less than three bowel movements daily and no disease recurrence within 60 days without additional treatment, was observed in 34 of 51 patients who received FMT (66.7%) compared with 30 of 49 of those receiving vancomycin (61.2%; difference, 5.4 percentage points; P for noninferiority < .001).
The results contradict the theory that response to FMT is 25 percentage points lower than response to vancomycin, the authors noted.
The proportion of patients with clinical cure at day 14 was 70.6% in the FMT group and 77.6% in the vancomycin group, and among those patients, two (5.6%) in the FMT group had disease recurrence compared with eight (21.1%) in the vancomycin group between days 15 and 60.
In the FMT group, 11 patients received additional treatment compared with four in the vancomycin group, predominantly oral vancomycin in both groups.
Despite the high rates of severe comorbidity among the patients at baseline, a subgroup analyses showed no significant differences in treatment effects based on factors including sex, age group, Charlson Comorbidity Index score, or CDI severity.
Importantly, there were also no significant differences in adverse events between the groups.
“Our results indicate that it is reasonable to treat patients with primary CDI with FMT and provide antibiotics only to patients with ongoing symptoms or recurrence after FMT,” the authors concluded.
FMT Faces Challenges in the US
FMT specifically consists of direct instillation of fecal matter to the upper gastrointestinal tract, via capsules or duodenal infusion, or the lower gastrointestinal tract via colonoscopy or enema.
While an AGA guideline issued in 2024 endorsed FMT for the prevention of recurrent, refractory, or fulminant CDI in select adults not responding to standard antibiotics, the association underscored important caveats, including a low quality of evidence, and concluded that FMT could not yet be recommended for other gastrointestinal conditions.
The treatment meanwhile has faced an uphill battle in the US. The provision of screened FMT inocula through the nonprofit OpenBiome, previously the country’s largest stool bank, was recently suspended amid FDA policy changes.
And while other commercial-grade biotherapeutic products Rebyota and Vowst, have received FDA approval, cost and insurance coverage can be significant barriers, said Elizabeth Hohmann, MD, of the Infectious Disease Division at Massachusetts General Hospital, Boston, in an editorial published with the study.
“Currently approved options are expensive and are not available to many who might benefit for various reasons, primarily cost,” she said.
Acceptance Higher in Europe
In Europe, and particularly Norway, acceptance of FMT for CDI and other indications has been more favorable, and while regulation of the treatment has varied among European countries, a new regulation to be implemented by the European Union in 2027 will improve standardization of the production, handling, storage, and other factors of FMT, Juul told GI & Hepatology News.
“I believe the new regulations will make the treatment more available to patients, and a standardization of the FMT production will make future trials more comparable and useful across countries,” he said.
Juul said he further expects that “our results will lower the threshold for choosing FMT as treatment in primary infections. I know that Denmark also gives FMT to patients with primary CDI.”
Quality of Life
Hohmann, who has treated many patients with recurrent CDI with FMT, noted that a key factor that should be underscored is how much better patients can feel after the treatment.
“Although there are no quality of life surveys in [the current study], had they been done, I suspect quality of life might have been higher in the FMT group; in my experience, people feel better after microbiome restoration.”
She added that her patients “report feeling much better, and that’s why I keep doing it,” she said. “I’ve had an 80-year-old patient tell me he’s going back to snow shoveling; another saying she can return to yoga classes.”
“When you have had bad gut microbiome dysbiosis that becomes normal, you feel a lot better,” Hohmann said.
In the treatment of primary CDI, however, Hohmann said the prospects, at least in the US, are likely slim.
“I do not believe that we in the United States will see FMT as a primary treatment of C difficile infection anytime soon,” she wrote in the editorial.
Nevertheless, Hohmann asserted that “FMT should remain available, with appropriate sources of carefully screened inocula for care and for further research into the many illnesses and therapies that are influenced by the health of the gut microbiome.”
This study received funding from the South-East Norway Health Trust. Hohmann had no disclosures to report.
A version of this article appeared on Medscape.com.
, with efficacy that is comparable to the standard treatment of vancomycin, and in some measures, showing even stronger efficacy, new research showed.
“FMT, prepared and administered according to international guidelines, is an effective and safe treatment option for C difficile infections, which should be considered for all patients with the infection,” first author Frederik Emil Juul, MD, PhD, of the Clinical Effectiveness Research Group, University of Oslo, in Oslo, Norway, told GI & Hepatology News.
FMT even showed a numerical superiority to vancomycin, which, though not statistically significant, “indicates that FMT has the potential to change the current practice of antibiotic therapy and may establish FMT as a first-line treatment for primary CDI,” the authors further asserted in the study, published recently in the Annals of Internal Medicine.
In the treatment of antibiotic-associated colitis due to CDI, vancomycin or fidaxomicin are the standard therapies, yet up to 20% of patients experience one or more symptom recurrences following successful initial antibiotic treatment, prompting the need for continued antibiotic regimens, resulting in increased costs and potential adverse events, while contributing to antibiotic resistance.
FMT, designed to restore a normal functional colonic microenvironment with the transfer of a healthy person’s stool, though still somewhat controversial, has gained acceptance and favor in recent years in the treatment of recurrent CDI, however, research has been lacking on its efficacy in the treatment of primary CDI.
With a previous proof-of-concept trial and observational study showing promising results in primary CDI, Juul and colleagues conducted the current randomized, open-label noninferiority trial.
For the multi-center study, 100 adult patients with CDI, defined as C diff toxin in stool and at least three loose stools daily, and no previous CDI within 1 year prior to enrollment, were randomized at 20 hospitals in Norway to receive either FMT, administered as an enema, without antibiotic pretreatment, or oral vancomycin at a dose of 125 mg, four times daily for 10 days.
The patients had a median age of about 70 years; more than 40% of patients had a Charlson Comorbidity Index score of ≥ 4, indicating severe comorbidity, and a third had severe CDI.
With the trial showing favorable results, a data and safety monitoring board recommended stopping the trial for efficacy and noninferiority after about half of the planned enrollment was reached.
The primary endpoint of a clinical cure, defined as firm stools or less than three bowel movements daily and no disease recurrence within 60 days without additional treatment, was observed in 34 of 51 patients who received FMT (66.7%) compared with 30 of 49 of those receiving vancomycin (61.2%; difference, 5.4 percentage points; P for noninferiority < .001).
The results contradict the theory that response to FMT is 25 percentage points lower than response to vancomycin, the authors noted.
The proportion of patients with clinical cure at day 14 was 70.6% in the FMT group and 77.6% in the vancomycin group, and among those patients, two (5.6%) in the FMT group had disease recurrence compared with eight (21.1%) in the vancomycin group between days 15 and 60.
In the FMT group, 11 patients received additional treatment compared with four in the vancomycin group, predominantly oral vancomycin in both groups.
Despite the high rates of severe comorbidity among the patients at baseline, a subgroup analyses showed no significant differences in treatment effects based on factors including sex, age group, Charlson Comorbidity Index score, or CDI severity.
Importantly, there were also no significant differences in adverse events between the groups.
“Our results indicate that it is reasonable to treat patients with primary CDI with FMT and provide antibiotics only to patients with ongoing symptoms or recurrence after FMT,” the authors concluded.
FMT Faces Challenges in the US
FMT specifically consists of direct instillation of fecal matter to the upper gastrointestinal tract, via capsules or duodenal infusion, or the lower gastrointestinal tract via colonoscopy or enema.
While an AGA guideline issued in 2024 endorsed FMT for the prevention of recurrent, refractory, or fulminant CDI in select adults not responding to standard antibiotics, the association underscored important caveats, including a low quality of evidence, and concluded that FMT could not yet be recommended for other gastrointestinal conditions.
The treatment meanwhile has faced an uphill battle in the US. The provision of screened FMT inocula through the nonprofit OpenBiome, previously the country’s largest stool bank, was recently suspended amid FDA policy changes.
And while other commercial-grade biotherapeutic products Rebyota and Vowst, have received FDA approval, cost and insurance coverage can be significant barriers, said Elizabeth Hohmann, MD, of the Infectious Disease Division at Massachusetts General Hospital, Boston, in an editorial published with the study.
“Currently approved options are expensive and are not available to many who might benefit for various reasons, primarily cost,” she said.
Acceptance Higher in Europe
In Europe, and particularly Norway, acceptance of FMT for CDI and other indications has been more favorable, and while regulation of the treatment has varied among European countries, a new regulation to be implemented by the European Union in 2027 will improve standardization of the production, handling, storage, and other factors of FMT, Juul told GI & Hepatology News.
“I believe the new regulations will make the treatment more available to patients, and a standardization of the FMT production will make future trials more comparable and useful across countries,” he said.
Juul said he further expects that “our results will lower the threshold for choosing FMT as treatment in primary infections. I know that Denmark also gives FMT to patients with primary CDI.”
Quality of Life
Hohmann, who has treated many patients with recurrent CDI with FMT, noted that a key factor that should be underscored is how much better patients can feel after the treatment.
“Although there are no quality of life surveys in [the current study], had they been done, I suspect quality of life might have been higher in the FMT group; in my experience, people feel better after microbiome restoration.”
She added that her patients “report feeling much better, and that’s why I keep doing it,” she said. “I’ve had an 80-year-old patient tell me he’s going back to snow shoveling; another saying she can return to yoga classes.”
“When you have had bad gut microbiome dysbiosis that becomes normal, you feel a lot better,” Hohmann said.
In the treatment of primary CDI, however, Hohmann said the prospects, at least in the US, are likely slim.
“I do not believe that we in the United States will see FMT as a primary treatment of C difficile infection anytime soon,” she wrote in the editorial.
Nevertheless, Hohmann asserted that “FMT should remain available, with appropriate sources of carefully screened inocula for care and for further research into the many illnesses and therapies that are influenced by the health of the gut microbiome.”
This study received funding from the South-East Norway Health Trust. Hohmann had no disclosures to report.
A version of this article appeared on Medscape.com.
Withdrawing Anti-TNF in IBD Remission: New Data
In the Spanish EXIT study, anti-TNF withdrawal in selected patients with IBD in clinical, endoscopic, and radiological remission had no impact on sustained clinical remission at 1 year, although objective markers of activity were higher in patients who stopped treatment.
The discontinuation of anti-TNF treatment “could be considered as an option” for a selected group of patients, said the authors led by Javier Gisbert, MD, PhD, with Autonomous University of Madrid.
However, the higher proportion of patients with elevated fecal calprotectin and significant endoscopic lesions at the end of follow-up “calls for caution and should be considered when discontinuing treatment in patients,” Gisbert and colleagues concluded.
The EXIT study results were published in the journal Gut (2025 Feb. doi: 10.1136/gutjnl-2024-333385).
Risky Business?
Anti-TNF drugs have reshaped IBD treatment but bring infection risks and costs, prompting interest in planned withdrawal after stable remission.
Yet prior evidence has been mixed. A meta-analysis of 27 studies suggested higher relapse after stopping anti-TNF therapy. However, the results were heterogeneous and most of the studies were retrospective, with a low number of patients and without a control group to compare with.
Clinical trials that have assessed the risk for relapse after discontinuation of anti-TNF therapy generally favored maintenance but had notable limitations.
The EXIT trial was conducted at 33 IBD units across Spain. A total of 140 patients in steroid-free clinical remission for ≥ 6 months on standard-dose infliximab or adalimumab were randomized (1:1) to either continue anti-TNF or switch to placebo matched to the drug they had been taking. All patients continued on immunomodulator therapy.
At 1 year, the proportion of patients with sustained clinical remission (primary outcome) was similar between patients who continued anti-TNF therapy and peers who stopped the medication (76% and 84%, respectively).
However, the proportion of patients with significant endoscopic lesions at the end of follow-up was higher in those who withdrew anti-TNF therapy (19% vs 8.5%; P = .01). Elevated fecal calprotectin (> 250 µg/g) was more common after withdrawal (33% vs 13%; P = .01).
Fecal calprotectin > 250 µg/g at baseline predicted lower odds of sustained remission and higher risk for losing remission — and was the only factor associated with lower likelihood of sustained remission.
Common Clinical Question
“When a patient starts an advanced biologic therapy, they often ask — will I be able to stop it?” Jean-Frederic Colombel, MD, director of the Inflammatory Bowel Disease Clinical Center at the Icahn School of Medicine at Mount Sinai, New York City, who wasn’t involved in the study, told GI & Hepatology News.
Generally speaking, Colombel said he tells patients, “If the drug is working well and you are in deep remission, they should try to avoid stopping because there is a risk of relapse. And with relapse, we never know if the drug will work again and maybe we’ll have to switch to another medication.”
“It’s an individualized discussion and decision and patients who do opt to stop [anti-TNF therapy] need to be monitored closely,” Colombel said.
Colombel cautioned that the study had a relatively short 1-year follow-up and those that stopped anti-TNF therapy had evidence of recurrent inflammation.
“Even though it didn’t translate yet to clinical relapse, there were more patients with subclinical active disease in the group that stopped as compared to the group that continued,” Colombel said.
He also noted that in the SPARE trial of patients with Crohn’s disease in clinical remission, patients who stopped infliximab had a higher risk for relapse compared with patients who stopped azathioprine and those who continued the combination therapy.
The EXIT study was supported by grants from Instituto de Salud Carlos III, Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa and AbbVie. Gisbert reported serving as speaker, consultant, and advisory member for or receiving research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma. Colombel had no relevant disclosures.
A version of this article appeared on Medscape.com.
In the Spanish EXIT study, anti-TNF withdrawal in selected patients with IBD in clinical, endoscopic, and radiological remission had no impact on sustained clinical remission at 1 year, although objective markers of activity were higher in patients who stopped treatment.
The discontinuation of anti-TNF treatment “could be considered as an option” for a selected group of patients, said the authors led by Javier Gisbert, MD, PhD, with Autonomous University of Madrid.
However, the higher proportion of patients with elevated fecal calprotectin and significant endoscopic lesions at the end of follow-up “calls for caution and should be considered when discontinuing treatment in patients,” Gisbert and colleagues concluded.
The EXIT study results were published in the journal Gut (2025 Feb. doi: 10.1136/gutjnl-2024-333385).
Risky Business?
Anti-TNF drugs have reshaped IBD treatment but bring infection risks and costs, prompting interest in planned withdrawal after stable remission.
Yet prior evidence has been mixed. A meta-analysis of 27 studies suggested higher relapse after stopping anti-TNF therapy. However, the results were heterogeneous and most of the studies were retrospective, with a low number of patients and without a control group to compare with.
Clinical trials that have assessed the risk for relapse after discontinuation of anti-TNF therapy generally favored maintenance but had notable limitations.
The EXIT trial was conducted at 33 IBD units across Spain. A total of 140 patients in steroid-free clinical remission for ≥ 6 months on standard-dose infliximab or adalimumab were randomized (1:1) to either continue anti-TNF or switch to placebo matched to the drug they had been taking. All patients continued on immunomodulator therapy.
At 1 year, the proportion of patients with sustained clinical remission (primary outcome) was similar between patients who continued anti-TNF therapy and peers who stopped the medication (76% and 84%, respectively).
However, the proportion of patients with significant endoscopic lesions at the end of follow-up was higher in those who withdrew anti-TNF therapy (19% vs 8.5%; P = .01). Elevated fecal calprotectin (> 250 µg/g) was more common after withdrawal (33% vs 13%; P = .01).
Fecal calprotectin > 250 µg/g at baseline predicted lower odds of sustained remission and higher risk for losing remission — and was the only factor associated with lower likelihood of sustained remission.
Common Clinical Question
“When a patient starts an advanced biologic therapy, they often ask — will I be able to stop it?” Jean-Frederic Colombel, MD, director of the Inflammatory Bowel Disease Clinical Center at the Icahn School of Medicine at Mount Sinai, New York City, who wasn’t involved in the study, told GI & Hepatology News.
Generally speaking, Colombel said he tells patients, “If the drug is working well and you are in deep remission, they should try to avoid stopping because there is a risk of relapse. And with relapse, we never know if the drug will work again and maybe we’ll have to switch to another medication.”
“It’s an individualized discussion and decision and patients who do opt to stop [anti-TNF therapy] need to be monitored closely,” Colombel said.
Colombel cautioned that the study had a relatively short 1-year follow-up and those that stopped anti-TNF therapy had evidence of recurrent inflammation.
“Even though it didn’t translate yet to clinical relapse, there were more patients with subclinical active disease in the group that stopped as compared to the group that continued,” Colombel said.
He also noted that in the SPARE trial of patients with Crohn’s disease in clinical remission, patients who stopped infliximab had a higher risk for relapse compared with patients who stopped azathioprine and those who continued the combination therapy.
The EXIT study was supported by grants from Instituto de Salud Carlos III, Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa and AbbVie. Gisbert reported serving as speaker, consultant, and advisory member for or receiving research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma. Colombel had no relevant disclosures.
A version of this article appeared on Medscape.com.
In the Spanish EXIT study, anti-TNF withdrawal in selected patients with IBD in clinical, endoscopic, and radiological remission had no impact on sustained clinical remission at 1 year, although objective markers of activity were higher in patients who stopped treatment.
The discontinuation of anti-TNF treatment “could be considered as an option” for a selected group of patients, said the authors led by Javier Gisbert, MD, PhD, with Autonomous University of Madrid.
However, the higher proportion of patients with elevated fecal calprotectin and significant endoscopic lesions at the end of follow-up “calls for caution and should be considered when discontinuing treatment in patients,” Gisbert and colleagues concluded.
The EXIT study results were published in the journal Gut (2025 Feb. doi: 10.1136/gutjnl-2024-333385).
Risky Business?
Anti-TNF drugs have reshaped IBD treatment but bring infection risks and costs, prompting interest in planned withdrawal after stable remission.
Yet prior evidence has been mixed. A meta-analysis of 27 studies suggested higher relapse after stopping anti-TNF therapy. However, the results were heterogeneous and most of the studies were retrospective, with a low number of patients and without a control group to compare with.
Clinical trials that have assessed the risk for relapse after discontinuation of anti-TNF therapy generally favored maintenance but had notable limitations.
The EXIT trial was conducted at 33 IBD units across Spain. A total of 140 patients in steroid-free clinical remission for ≥ 6 months on standard-dose infliximab or adalimumab were randomized (1:1) to either continue anti-TNF or switch to placebo matched to the drug they had been taking. All patients continued on immunomodulator therapy.
At 1 year, the proportion of patients with sustained clinical remission (primary outcome) was similar between patients who continued anti-TNF therapy and peers who stopped the medication (76% and 84%, respectively).
However, the proportion of patients with significant endoscopic lesions at the end of follow-up was higher in those who withdrew anti-TNF therapy (19% vs 8.5%; P = .01). Elevated fecal calprotectin (> 250 µg/g) was more common after withdrawal (33% vs 13%; P = .01).
Fecal calprotectin > 250 µg/g at baseline predicted lower odds of sustained remission and higher risk for losing remission — and was the only factor associated with lower likelihood of sustained remission.
Common Clinical Question
“When a patient starts an advanced biologic therapy, they often ask — will I be able to stop it?” Jean-Frederic Colombel, MD, director of the Inflammatory Bowel Disease Clinical Center at the Icahn School of Medicine at Mount Sinai, New York City, who wasn’t involved in the study, told GI & Hepatology News.
Generally speaking, Colombel said he tells patients, “If the drug is working well and you are in deep remission, they should try to avoid stopping because there is a risk of relapse. And with relapse, we never know if the drug will work again and maybe we’ll have to switch to another medication.”
“It’s an individualized discussion and decision and patients who do opt to stop [anti-TNF therapy] need to be monitored closely,” Colombel said.
Colombel cautioned that the study had a relatively short 1-year follow-up and those that stopped anti-TNF therapy had evidence of recurrent inflammation.
“Even though it didn’t translate yet to clinical relapse, there were more patients with subclinical active disease in the group that stopped as compared to the group that continued,” Colombel said.
He also noted that in the SPARE trial of patients with Crohn’s disease in clinical remission, patients who stopped infliximab had a higher risk for relapse compared with patients who stopped azathioprine and those who continued the combination therapy.
The EXIT study was supported by grants from Instituto de Salud Carlos III, Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa and AbbVie. Gisbert reported serving as speaker, consultant, and advisory member for or receiving research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma. Colombel had no relevant disclosures.
A version of this article appeared on Medscape.com.
Oral Microbes Tied to Pancreatic Cancer Risk
Could oral microbiome profiling help spot people at risk for pancreatic cancer?
It may be possible, according to a recent analysis published in JAMA Oncology.
Researchers found that , which could be a step toward earlier detection of the deadly malignancy.
“We identified 27 individual bacterial and fungal species significantly associated with pancreatic cancer development,” said Jiyoung Ahn, PhD, of NYU Grossman School of Medicine in New York City.
“If validated, oral microbiome profiling could serve as a noninvasive biomarker to identify individuals at elevated risk who might benefit from enhanced surveillance,” Ahn told GI & Hepatology News by email.
Rates of pancreatic cancer are on the rise. But detecting the disease before it becomes unresectable has remained an elusive goal, and the US Preventive Services Task Force discourages screening of asymptomatic adults.
For their study, Ahn and her colleagues analyzed data from 122,000 participants who provided oral wash samples as part of two cohort studies conducted in the US. The researchers used whole-genome shotgun sequencing and internal transcribed spacer sequencing to identity the bacterial and fungal species in the samples, respectively.
Over a median follow-up of nearly 9 years, 445 people developed pancreatic cancer and were matched with 445 who did not. Three oral bacterial periodontal pathogens — Porphyromonas gingivalis (odds ratio [OR], 1.27), Eubacterium nodatum (OR, 1.42), and Parvimonas micra (OR, 1.36) — as well as the fungal genus Candida were all linked to significantly increased odds of developing pancreatic cancer.
In a bacteriome-wide scan, the researchers pinpointed another 20 oral bacteria associated with pancreatic cancer — eight with a decreased risk and 13 with an increased risk for the disease.
The researchers also calculated a microbial risk score, which was the weighted sum of the relative abundance of bacterial and fungal species. In a meta-analysis of data from the two cohorts, the microbial risk score derived from 23 bacterial species and four fungal species, including various Candida species, was associated with pancreatic cancer (multivariate OR per 1-SD increase in the score, 3.44; 95% CI, 2.63-4.51).
“The oral microbiota holds promise as a biomarker to identify individuals at high risk of pancreatic cancer, potentially enabling personalized pancreatic cancer prevention,” Ahn and her colleagues concluded.
But Gil Welch, MD, of Brigham and Women’s Hospital in Boston, who has written about screening for decades, isn’t so sure.
Given the “impressive volume of information” included in the analysis, “it is not surprising that the investigators are able to create a microbial risk score (based on 27 species of bacteria and fungi) that is highly related to pancreatic cancer,” Welch said. “The authors are careful to emphasize these are associations, not causal relationships.”
But even if the relationship were causal, finding more people with the malignancy can also have downsides, said Welch.
In a study out last year, Welch and colleagues found that while the incidence of pancreatic cancer among young Americans has been rising, mortality rates in this demographic haven’t budged, suggesting a potential for overdiagnosis.
“Screening for pancreatic cancer has never been shown to reduce pancreatic cancer mortality,” Welch told GI & Hepatology News. “Why screen large swaths of the population simply to enumerate ‘risk factors’ for an unproven benefit that, at best, could help only a few? Meanwhile, the burdens for everyone else are real: the mental and financial strains of ‘high risk’ labels, false alarms, and endless follow-ups. It’s a recipe to make us all worried sick — and poorer.”
Ahn reported having no disclosures. Welch reported receiving royalties from three books including “Should I be tested for cancer?”
A version of this article appeared on Medscape.com.
Could oral microbiome profiling help spot people at risk for pancreatic cancer?
It may be possible, according to a recent analysis published in JAMA Oncology.
Researchers found that , which could be a step toward earlier detection of the deadly malignancy.
“We identified 27 individual bacterial and fungal species significantly associated with pancreatic cancer development,” said Jiyoung Ahn, PhD, of NYU Grossman School of Medicine in New York City.
“If validated, oral microbiome profiling could serve as a noninvasive biomarker to identify individuals at elevated risk who might benefit from enhanced surveillance,” Ahn told GI & Hepatology News by email.
Rates of pancreatic cancer are on the rise. But detecting the disease before it becomes unresectable has remained an elusive goal, and the US Preventive Services Task Force discourages screening of asymptomatic adults.
For their study, Ahn and her colleagues analyzed data from 122,000 participants who provided oral wash samples as part of two cohort studies conducted in the US. The researchers used whole-genome shotgun sequencing and internal transcribed spacer sequencing to identity the bacterial and fungal species in the samples, respectively.
Over a median follow-up of nearly 9 years, 445 people developed pancreatic cancer and were matched with 445 who did not. Three oral bacterial periodontal pathogens — Porphyromonas gingivalis (odds ratio [OR], 1.27), Eubacterium nodatum (OR, 1.42), and Parvimonas micra (OR, 1.36) — as well as the fungal genus Candida were all linked to significantly increased odds of developing pancreatic cancer.
In a bacteriome-wide scan, the researchers pinpointed another 20 oral bacteria associated with pancreatic cancer — eight with a decreased risk and 13 with an increased risk for the disease.
The researchers also calculated a microbial risk score, which was the weighted sum of the relative abundance of bacterial and fungal species. In a meta-analysis of data from the two cohorts, the microbial risk score derived from 23 bacterial species and four fungal species, including various Candida species, was associated with pancreatic cancer (multivariate OR per 1-SD increase in the score, 3.44; 95% CI, 2.63-4.51).
“The oral microbiota holds promise as a biomarker to identify individuals at high risk of pancreatic cancer, potentially enabling personalized pancreatic cancer prevention,” Ahn and her colleagues concluded.
But Gil Welch, MD, of Brigham and Women’s Hospital in Boston, who has written about screening for decades, isn’t so sure.
Given the “impressive volume of information” included in the analysis, “it is not surprising that the investigators are able to create a microbial risk score (based on 27 species of bacteria and fungi) that is highly related to pancreatic cancer,” Welch said. “The authors are careful to emphasize these are associations, not causal relationships.”
But even if the relationship were causal, finding more people with the malignancy can also have downsides, said Welch.
In a study out last year, Welch and colleagues found that while the incidence of pancreatic cancer among young Americans has been rising, mortality rates in this demographic haven’t budged, suggesting a potential for overdiagnosis.
“Screening for pancreatic cancer has never been shown to reduce pancreatic cancer mortality,” Welch told GI & Hepatology News. “Why screen large swaths of the population simply to enumerate ‘risk factors’ for an unproven benefit that, at best, could help only a few? Meanwhile, the burdens for everyone else are real: the mental and financial strains of ‘high risk’ labels, false alarms, and endless follow-ups. It’s a recipe to make us all worried sick — and poorer.”
Ahn reported having no disclosures. Welch reported receiving royalties from three books including “Should I be tested for cancer?”
A version of this article appeared on Medscape.com.
Could oral microbiome profiling help spot people at risk for pancreatic cancer?
It may be possible, according to a recent analysis published in JAMA Oncology.
Researchers found that , which could be a step toward earlier detection of the deadly malignancy.
“We identified 27 individual bacterial and fungal species significantly associated with pancreatic cancer development,” said Jiyoung Ahn, PhD, of NYU Grossman School of Medicine in New York City.
“If validated, oral microbiome profiling could serve as a noninvasive biomarker to identify individuals at elevated risk who might benefit from enhanced surveillance,” Ahn told GI & Hepatology News by email.
Rates of pancreatic cancer are on the rise. But detecting the disease before it becomes unresectable has remained an elusive goal, and the US Preventive Services Task Force discourages screening of asymptomatic adults.
For their study, Ahn and her colleagues analyzed data from 122,000 participants who provided oral wash samples as part of two cohort studies conducted in the US. The researchers used whole-genome shotgun sequencing and internal transcribed spacer sequencing to identity the bacterial and fungal species in the samples, respectively.
Over a median follow-up of nearly 9 years, 445 people developed pancreatic cancer and were matched with 445 who did not. Three oral bacterial periodontal pathogens — Porphyromonas gingivalis (odds ratio [OR], 1.27), Eubacterium nodatum (OR, 1.42), and Parvimonas micra (OR, 1.36) — as well as the fungal genus Candida were all linked to significantly increased odds of developing pancreatic cancer.
In a bacteriome-wide scan, the researchers pinpointed another 20 oral bacteria associated with pancreatic cancer — eight with a decreased risk and 13 with an increased risk for the disease.
The researchers also calculated a microbial risk score, which was the weighted sum of the relative abundance of bacterial and fungal species. In a meta-analysis of data from the two cohorts, the microbial risk score derived from 23 bacterial species and four fungal species, including various Candida species, was associated with pancreatic cancer (multivariate OR per 1-SD increase in the score, 3.44; 95% CI, 2.63-4.51).
“The oral microbiota holds promise as a biomarker to identify individuals at high risk of pancreatic cancer, potentially enabling personalized pancreatic cancer prevention,” Ahn and her colleagues concluded.
But Gil Welch, MD, of Brigham and Women’s Hospital in Boston, who has written about screening for decades, isn’t so sure.
Given the “impressive volume of information” included in the analysis, “it is not surprising that the investigators are able to create a microbial risk score (based on 27 species of bacteria and fungi) that is highly related to pancreatic cancer,” Welch said. “The authors are careful to emphasize these are associations, not causal relationships.”
But even if the relationship were causal, finding more people with the malignancy can also have downsides, said Welch.
In a study out last year, Welch and colleagues found that while the incidence of pancreatic cancer among young Americans has been rising, mortality rates in this demographic haven’t budged, suggesting a potential for overdiagnosis.
“Screening for pancreatic cancer has never been shown to reduce pancreatic cancer mortality,” Welch told GI & Hepatology News. “Why screen large swaths of the population simply to enumerate ‘risk factors’ for an unproven benefit that, at best, could help only a few? Meanwhile, the burdens for everyone else are real: the mental and financial strains of ‘high risk’ labels, false alarms, and endless follow-ups. It’s a recipe to make us all worried sick — and poorer.”
Ahn reported having no disclosures. Welch reported receiving royalties from three books including “Should I be tested for cancer?”
A version of this article appeared on Medscape.com.
How Chronic Stress Disrupts the Gut Microbiome
Chronic psychological stress is common. A 2023 survey revealed that about one quarter of US adults reported high stress levels, and three quarters reported that chronic stress affects their daily lives.
Emerging evidence suggests that chronic stress not only exacts a high toll on mental health but also can wreak havoc on all levels of gastrointestinal (GI) functioning, all the way down to the microbiome.
Aasma Shaukat, MD, MPH, AGAF, gastroenterologist with NYU Langone Health and director of GI Outcomes Research, Gastroenterology at NYU Grossman School of Medicine in New York City, said in an interview with GI & Hepatology News.
“This basically means that the normal balance of microorganisms that essentially we think are beneficial gets reduced, and the colonies considered to be more harmful proliferate,” she explained.
What Does the Science Tell Us?
Numerous studies published in the past 5 years have linked chronic stress to modest but reproducible shifts in the composition of the microbiome.
A study of frontline healthcare workers during COVID-19 revealed that the pandemic was associated with significant depression, anxiety, and stress, as well as gut dysbiosis that persisted for at least half a year.
Notably, healthcare workers had low gut alpha diversity, indicating a less resilient and diverse microbiome, a state often associated with dysbiosis and increased risk for various diseases and negative health outcomes.
A two-cohort study of healthy adults found higher alpha diversity in those reporting low stress levels. It also found a link between stress and enriched levels of Escherichia/Shigella, an overgrowth of which has been linked to various conditions, including inflammatory bowel disease.
In addition, a 2023 systematic review of human studies concluded that stress is associated with changes in specific genera — namely reductions in gut-healthy Lachnospira/Lachnospiraceae and Phascolarctobacterium, which produce beneficial short-chain fatty acids that support the health of the intestinal lining and modulate the immune system.
Stress during specific life stages also appears to alter the gut microbiome.
For example, in a study of postpartum women, those at an increased risk for parenting stress showed lower alpha diversity on the Shannon diversity index.
Research involving mother-child pairs tied adversity — such as maltreatment of the mother during her childhood, prenatal anxiety, and hardship in the child’s early life — to distinct microbiome profiles in 2-year-olds, supporting a stress-microbiome pathway relevant to socioemotional outcomes, the authors said.
Emerging evidence indicates a link between the gut microbiome and posttraumatic stress disorder (PTSD).
A recent systematic review found differences in gut microbial taxa between individuals with PTSD and trauma-exposed controls without PTSD. A separate analysis pointed to a potential causal impact of gut microbiomes on the development of PTSD.
Mechanisms Behind the Link
Stress interferes with the brain’s production of neurotransmitters, such as serotonin, which controls anxiety, mood, sleep, and many other functions in the brain, Shaukat told GI & Hepatology News.
“But serotonin also crosses the blood-brain barrier, and actually, the gut has more serotonin receptors than the brain, so an imbalance of serotonin can actually affect the gut microbiome through signaling at the neurotransmitter level,” Shaukat explained.
Stress can also affect sleep, and sleep itself has regulatory properties for gut bacteria, Shaukat noted.
“Stress also lowers our immunity, and this can make the gut barrier susceptible or permeable to bacterial toxins that can pass through and breach the gut barrier and be released into the bloodstream, which can trigger inflammation,” Shaukat explained.
Implications for Patient Care
The gut-brain-microbiome axis remains an emerging field of study. “We’re learning more and more about this, and we need to because the microbial colonies are so diverse and we haven’t nailed it down yet,” Shaukat said.
In the meantime, what can clinicians tell patients?
Aside from managing stress, which “is easier said than done,” patients can improve their diet, Shaukat said.
“What we tell patients is to essentially increase their intake of gut-friendly foods that preferentially grow the bacterial colonies that are beneficial for us,” Shaukat said. This includes fermented foods, yogurt, kimchi, chia seeds, kombucha, pickled vegetables, and whole grains.
A recent randomized controlled trial of healthy adults found a “psychobiotic diet” — a diet high in prebiotic and fermented foods — was associated with less perceived stress and subtle beneficial shifts in microbial composition.
“These foods can help keep the gut in good health and may actually also reduce or mitigate some of the effects of stress,” Shaukat said.
“Eating well is something I think we should all think about and maybe prioritize when we’re going through a stressful situation or looking to kind of mitigate the effects of stress and the anxiety and depression it can cause,” she advised.
Shaukat said she also encourages patients to engage in regular physical activity, which benefits the gut microbiome by helping to regulate gut motility. Exercise can also boost mood and help relieve stress.
“A balanced Mediterranean diet and regular activity is truly the secret for gut health,” Shaukat said.
Patients may be tempted by the probiotic supplements lining drugstore shelves, but there “isn’t great evidence for probiotic supplements,” she said. “What we can get from dietary sources far outweighs what can be put in a pill.”
Shaukat disclosed having no relevant disclosures.
A version of this article appeared on Medscape.com.
Chronic psychological stress is common. A 2023 survey revealed that about one quarter of US adults reported high stress levels, and three quarters reported that chronic stress affects their daily lives.
Emerging evidence suggests that chronic stress not only exacts a high toll on mental health but also can wreak havoc on all levels of gastrointestinal (GI) functioning, all the way down to the microbiome.
Aasma Shaukat, MD, MPH, AGAF, gastroenterologist with NYU Langone Health and director of GI Outcomes Research, Gastroenterology at NYU Grossman School of Medicine in New York City, said in an interview with GI & Hepatology News.
“This basically means that the normal balance of microorganisms that essentially we think are beneficial gets reduced, and the colonies considered to be more harmful proliferate,” she explained.
What Does the Science Tell Us?
Numerous studies published in the past 5 years have linked chronic stress to modest but reproducible shifts in the composition of the microbiome.
A study of frontline healthcare workers during COVID-19 revealed that the pandemic was associated with significant depression, anxiety, and stress, as well as gut dysbiosis that persisted for at least half a year.
Notably, healthcare workers had low gut alpha diversity, indicating a less resilient and diverse microbiome, a state often associated with dysbiosis and increased risk for various diseases and negative health outcomes.
A two-cohort study of healthy adults found higher alpha diversity in those reporting low stress levels. It also found a link between stress and enriched levels of Escherichia/Shigella, an overgrowth of which has been linked to various conditions, including inflammatory bowel disease.
In addition, a 2023 systematic review of human studies concluded that stress is associated with changes in specific genera — namely reductions in gut-healthy Lachnospira/Lachnospiraceae and Phascolarctobacterium, which produce beneficial short-chain fatty acids that support the health of the intestinal lining and modulate the immune system.
Stress during specific life stages also appears to alter the gut microbiome.
For example, in a study of postpartum women, those at an increased risk for parenting stress showed lower alpha diversity on the Shannon diversity index.
Research involving mother-child pairs tied adversity — such as maltreatment of the mother during her childhood, prenatal anxiety, and hardship in the child’s early life — to distinct microbiome profiles in 2-year-olds, supporting a stress-microbiome pathway relevant to socioemotional outcomes, the authors said.
Emerging evidence indicates a link between the gut microbiome and posttraumatic stress disorder (PTSD).
A recent systematic review found differences in gut microbial taxa between individuals with PTSD and trauma-exposed controls without PTSD. A separate analysis pointed to a potential causal impact of gut microbiomes on the development of PTSD.
Mechanisms Behind the Link
Stress interferes with the brain’s production of neurotransmitters, such as serotonin, which controls anxiety, mood, sleep, and many other functions in the brain, Shaukat told GI & Hepatology News.
“But serotonin also crosses the blood-brain barrier, and actually, the gut has more serotonin receptors than the brain, so an imbalance of serotonin can actually affect the gut microbiome through signaling at the neurotransmitter level,” Shaukat explained.
Stress can also affect sleep, and sleep itself has regulatory properties for gut bacteria, Shaukat noted.
“Stress also lowers our immunity, and this can make the gut barrier susceptible or permeable to bacterial toxins that can pass through and breach the gut barrier and be released into the bloodstream, which can trigger inflammation,” Shaukat explained.
Implications for Patient Care
The gut-brain-microbiome axis remains an emerging field of study. “We’re learning more and more about this, and we need to because the microbial colonies are so diverse and we haven’t nailed it down yet,” Shaukat said.
In the meantime, what can clinicians tell patients?
Aside from managing stress, which “is easier said than done,” patients can improve their diet, Shaukat said.
“What we tell patients is to essentially increase their intake of gut-friendly foods that preferentially grow the bacterial colonies that are beneficial for us,” Shaukat said. This includes fermented foods, yogurt, kimchi, chia seeds, kombucha, pickled vegetables, and whole grains.
A recent randomized controlled trial of healthy adults found a “psychobiotic diet” — a diet high in prebiotic and fermented foods — was associated with less perceived stress and subtle beneficial shifts in microbial composition.
“These foods can help keep the gut in good health and may actually also reduce or mitigate some of the effects of stress,” Shaukat said.
“Eating well is something I think we should all think about and maybe prioritize when we’re going through a stressful situation or looking to kind of mitigate the effects of stress and the anxiety and depression it can cause,” she advised.
Shaukat said she also encourages patients to engage in regular physical activity, which benefits the gut microbiome by helping to regulate gut motility. Exercise can also boost mood and help relieve stress.
“A balanced Mediterranean diet and regular activity is truly the secret for gut health,” Shaukat said.
Patients may be tempted by the probiotic supplements lining drugstore shelves, but there “isn’t great evidence for probiotic supplements,” she said. “What we can get from dietary sources far outweighs what can be put in a pill.”
Shaukat disclosed having no relevant disclosures.
A version of this article appeared on Medscape.com.
Chronic psychological stress is common. A 2023 survey revealed that about one quarter of US adults reported high stress levels, and three quarters reported that chronic stress affects their daily lives.
Emerging evidence suggests that chronic stress not only exacts a high toll on mental health but also can wreak havoc on all levels of gastrointestinal (GI) functioning, all the way down to the microbiome.
Aasma Shaukat, MD, MPH, AGAF, gastroenterologist with NYU Langone Health and director of GI Outcomes Research, Gastroenterology at NYU Grossman School of Medicine in New York City, said in an interview with GI & Hepatology News.
“This basically means that the normal balance of microorganisms that essentially we think are beneficial gets reduced, and the colonies considered to be more harmful proliferate,” she explained.
What Does the Science Tell Us?
Numerous studies published in the past 5 years have linked chronic stress to modest but reproducible shifts in the composition of the microbiome.
A study of frontline healthcare workers during COVID-19 revealed that the pandemic was associated with significant depression, anxiety, and stress, as well as gut dysbiosis that persisted for at least half a year.
Notably, healthcare workers had low gut alpha diversity, indicating a less resilient and diverse microbiome, a state often associated with dysbiosis and increased risk for various diseases and negative health outcomes.
A two-cohort study of healthy adults found higher alpha diversity in those reporting low stress levels. It also found a link between stress and enriched levels of Escherichia/Shigella, an overgrowth of which has been linked to various conditions, including inflammatory bowel disease.
In addition, a 2023 systematic review of human studies concluded that stress is associated with changes in specific genera — namely reductions in gut-healthy Lachnospira/Lachnospiraceae and Phascolarctobacterium, which produce beneficial short-chain fatty acids that support the health of the intestinal lining and modulate the immune system.
Stress during specific life stages also appears to alter the gut microbiome.
For example, in a study of postpartum women, those at an increased risk for parenting stress showed lower alpha diversity on the Shannon diversity index.
Research involving mother-child pairs tied adversity — such as maltreatment of the mother during her childhood, prenatal anxiety, and hardship in the child’s early life — to distinct microbiome profiles in 2-year-olds, supporting a stress-microbiome pathway relevant to socioemotional outcomes, the authors said.
Emerging evidence indicates a link between the gut microbiome and posttraumatic stress disorder (PTSD).
A recent systematic review found differences in gut microbial taxa between individuals with PTSD and trauma-exposed controls without PTSD. A separate analysis pointed to a potential causal impact of gut microbiomes on the development of PTSD.
Mechanisms Behind the Link
Stress interferes with the brain’s production of neurotransmitters, such as serotonin, which controls anxiety, mood, sleep, and many other functions in the brain, Shaukat told GI & Hepatology News.
“But serotonin also crosses the blood-brain barrier, and actually, the gut has more serotonin receptors than the brain, so an imbalance of serotonin can actually affect the gut microbiome through signaling at the neurotransmitter level,” Shaukat explained.
Stress can also affect sleep, and sleep itself has regulatory properties for gut bacteria, Shaukat noted.
“Stress also lowers our immunity, and this can make the gut barrier susceptible or permeable to bacterial toxins that can pass through and breach the gut barrier and be released into the bloodstream, which can trigger inflammation,” Shaukat explained.
Implications for Patient Care
The gut-brain-microbiome axis remains an emerging field of study. “We’re learning more and more about this, and we need to because the microbial colonies are so diverse and we haven’t nailed it down yet,” Shaukat said.
In the meantime, what can clinicians tell patients?
Aside from managing stress, which “is easier said than done,” patients can improve their diet, Shaukat said.
“What we tell patients is to essentially increase their intake of gut-friendly foods that preferentially grow the bacterial colonies that are beneficial for us,” Shaukat said. This includes fermented foods, yogurt, kimchi, chia seeds, kombucha, pickled vegetables, and whole grains.
A recent randomized controlled trial of healthy adults found a “psychobiotic diet” — a diet high in prebiotic and fermented foods — was associated with less perceived stress and subtle beneficial shifts in microbial composition.
“These foods can help keep the gut in good health and may actually also reduce or mitigate some of the effects of stress,” Shaukat said.
“Eating well is something I think we should all think about and maybe prioritize when we’re going through a stressful situation or looking to kind of mitigate the effects of stress and the anxiety and depression it can cause,” she advised.
Shaukat said she also encourages patients to engage in regular physical activity, which benefits the gut microbiome by helping to regulate gut motility. Exercise can also boost mood and help relieve stress.
“A balanced Mediterranean diet and regular activity is truly the secret for gut health,” Shaukat said.
Patients may be tempted by the probiotic supplements lining drugstore shelves, but there “isn’t great evidence for probiotic supplements,” she said. “What we can get from dietary sources far outweighs what can be put in a pill.”
Shaukat disclosed having no relevant disclosures.
A version of this article appeared on Medscape.com.