From the AGA Journals

Large language models (LLMs) may help streamline clinical guideline development by dramatically reducing the time and cost required for systematic reviews, according to a pilot study from the American Gastroenterological Association (AGA).

Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.

“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”

To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines. 

The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission. 

Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.

After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented. 

The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.

Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.

Comparable accuracy and time savings were observed for the other topics. 

The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.

Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.

The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.

“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”

This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
 

Large language models (LLMs) may help streamline clinical guideline development by dramatically reducing the time and cost required for systematic reviews, according to a pilot study from the American Gastroenterological Association (AGA).

Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.

“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”

To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines. 

The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission. 

Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.

After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented. 

The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.

Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.

Comparable accuracy and time savings were observed for the other topics. 

The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.

Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.

The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.

“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”

This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
 

Large language models (LLMs) may help streamline clinical guideline development by dramatically reducing the time and cost required for systematic reviews, according to a pilot study from the American Gastroenterological Association (AGA).

Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.

“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”

To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines. 

The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission. 

Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.

After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented. 

The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.

Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.

Comparable accuracy and time savings were observed for the other topics. 

The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.

Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.

The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.

“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”

This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
 

The first-ever global guidelines for pregnancy and inflammatory bowel disease (IBD) recommend continuing biologics and low-risk medications through pregnancy and lactation in women with IBD, suggesting this approach will not harm the fetus.

The guidelines also recommend that all women with IBD receive preconception counseling and be followed as high-risk pregnancies.

“Management of chronic illness in pregnant women has always been defined by fear of harming the fetus,” said Uma Mahadevan, MD, AGAF, director of the Colitis and Crohn’s Disease Center at the University of California San Francisco and chair of the Global Consensus Consortium that developed the guidelines. 

As a result, pregnant women are excluded from clinical trials of experimental therapies for IBD. And when a new therapy achieves regulatory approval, there are no human pregnancy safety data, only animal data. To fill this gap, the PIANO study, of which Mahadevan is principal investigator, looked at the safety of IBD medications in pregnancy and short- and long-term outcomes of the children.

“With our ongoing work in pregnancy in the patient with IBD, we realized that inflammation in the mother is the leading cause of poor outcome for the infant,” she told GI & Hepatology News. 

“We also have a better understanding of placental transfer of biologic agents” and the lack of exposure to the fetus during the first trimester, “a key period of organogenesis,” she added. 

Final recommendations were published simultaneously in six international journals, namely, Clinical Gastroenterology and Hepatology, American Journal of Gastroenterology, GUT, Inflammatory Bowel Diseases, Journal of Crohn’s and Colitis, and Alimentary Pharmacology and Therapeutics.

 

Surprising, Novel Findings

Limited provider knowledge led to varied practices in caring for women with IBD who become pregnant, according to the consensus authors. Practices are affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus. 

“The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike,” the authors of the guidelines wrote. 

Therefore, the Global Consensus Consortium — a group of 39 IBD experts, including teratologists and maternal fetal medicine specialists and seven patient advocates from six continents — convened to review and assess current data and come to an agreement on best practices. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used when sufficient published data were available, and the Research and Development process when expert opinion was needed to guide consistent practice.

“Some of the findings were expected, but others were novel,” said Mahadevan. 

Recommendations that might surprise clinicians include GRADE statement 9, which suggests that pregnant women with IBD take low-dose aspirin by 12 to 16 weeks’ gestation to prevent preterm preeclampsia. “This is based on the ASPRE study, showing that women at risk of preeclampsia can lower their risk by taking low-dose aspirin,” with no risk for flare, Mahadevan said.

In addition, GRADE statements 17-20 recommend/suggest that women continue their biologic throughout pregnancy without stopping. “North America has always recommended continuing during the third trimester, while Europe only recently has come to this,” Mahadevan said. “However, there was always some looseness about stopping at week X, Y, or Z. Now, we do recommend continuing the dose on schedule with no holding.”

Continuing medications considered low risk for use during pregnancy, such as 5-amino salicylic acids, sulfasalazine, thiopurines, and all monoclonal antibodies during preconception, pregnancy, and lactation, was also recommended. 

However, small-molecule drugs such as S1P receptor molecules and JAK inhibitors should be avoided for at least 1 month, and in some cases for 3 months prior to attempting conception, unless there is no alternative for the health of the mother. They should also be avoided during lactation.

Grade statement 33, which suggests that live rotavirus vaccine may be provided in children with in utero exposure to biologics, is also new, Mahadevan noted. “All prior recommendations were that no live vaccine should be given in the first 6 months or longer if infants were exposed to biologics in utero, but based on a prospective Canadian study, there is no harm when given to these infants.”

Another novel recommendation is that women with IBD on any monoclonal antibodies, including newer interleukin-23s, may breastfeed even though there are not clinical trial data at this point. The recommendation to continue them through pregnancy and lactation is based on placental physiology, as well as on the physiology of monoclonal antibody transfer in breast milk, according to the consortium.

Furthermore, the authors noted, there was no increase in infant infections at 4 months or 12 months if they were exposed to a biologic or thiopurine (or both) during pregnancy.

Overall, the consortium recommended that all pregnancies for women with IBD be considered as “high risk” for complications. This is due to the fact that many parts of the world, including the US, are “resource-limited,” Mahadevan explained. Since maternal fetal medicine specialists are not widely available, the consortium suggested all these patients be followed with increased monitoring and surveillance based on available resources.

In addition to the guidelines, patient videos in seven languages, a professional slide deck in English and Spanish, and a video on the global consensus are all available at https://pianostudy.org/.

This study was funded by The Leona B. and Harry H. Helmsley Charitable Trust.

Mahadevan reported being a consultant for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Merck, Pfizer, Protagonist, Roivant, and Takeda.

A version of this article appeared on Medscape.com. 

The first-ever global guidelines for pregnancy and inflammatory bowel disease (IBD) recommend continuing biologics and low-risk medications through pregnancy and lactation in women with IBD, suggesting this approach will not harm the fetus.

The guidelines also recommend that all women with IBD receive preconception counseling and be followed as high-risk pregnancies.

“Management of chronic illness in pregnant women has always been defined by fear of harming the fetus,” said Uma Mahadevan, MD, AGAF, director of the Colitis and Crohn’s Disease Center at the University of California San Francisco and chair of the Global Consensus Consortium that developed the guidelines. 

As a result, pregnant women are excluded from clinical trials of experimental therapies for IBD. And when a new therapy achieves regulatory approval, there are no human pregnancy safety data, only animal data. To fill this gap, the PIANO study, of which Mahadevan is principal investigator, looked at the safety of IBD medications in pregnancy and short- and long-term outcomes of the children.

“With our ongoing work in pregnancy in the patient with IBD, we realized that inflammation in the mother is the leading cause of poor outcome for the infant,” she told GI & Hepatology News. 

“We also have a better understanding of placental transfer of biologic agents” and the lack of exposure to the fetus during the first trimester, “a key period of organogenesis,” she added. 

Final recommendations were published simultaneously in six international journals, namely, Clinical Gastroenterology and Hepatology, American Journal of Gastroenterology, GUT, Inflammatory Bowel Diseases, Journal of Crohn’s and Colitis, and Alimentary Pharmacology and Therapeutics.

 

Surprising, Novel Findings

Limited provider knowledge led to varied practices in caring for women with IBD who become pregnant, according to the consensus authors. Practices are affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus. 

“The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike,” the authors of the guidelines wrote. 

Therefore, the Global Consensus Consortium — a group of 39 IBD experts, including teratologists and maternal fetal medicine specialists and seven patient advocates from six continents — convened to review and assess current data and come to an agreement on best practices. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used when sufficient published data were available, and the Research and Development process when expert opinion was needed to guide consistent practice.

“Some of the findings were expected, but others were novel,” said Mahadevan. 

Recommendations that might surprise clinicians include GRADE statement 9, which suggests that pregnant women with IBD take low-dose aspirin by 12 to 16 weeks’ gestation to prevent preterm preeclampsia. “This is based on the ASPRE study, showing that women at risk of preeclampsia can lower their risk by taking low-dose aspirin,” with no risk for flare, Mahadevan said.

In addition, GRADE statements 17-20 recommend/suggest that women continue their biologic throughout pregnancy without stopping. “North America has always recommended continuing during the third trimester, while Europe only recently has come to this,” Mahadevan said. “However, there was always some looseness about stopping at week X, Y, or Z. Now, we do recommend continuing the dose on schedule with no holding.”

Continuing medications considered low risk for use during pregnancy, such as 5-amino salicylic acids, sulfasalazine, thiopurines, and all monoclonal antibodies during preconception, pregnancy, and lactation, was also recommended. 

However, small-molecule drugs such as S1P receptor molecules and JAK inhibitors should be avoided for at least 1 month, and in some cases for 3 months prior to attempting conception, unless there is no alternative for the health of the mother. They should also be avoided during lactation.

Grade statement 33, which suggests that live rotavirus vaccine may be provided in children with in utero exposure to biologics, is also new, Mahadevan noted. “All prior recommendations were that no live vaccine should be given in the first 6 months or longer if infants were exposed to biologics in utero, but based on a prospective Canadian study, there is no harm when given to these infants.”

Another novel recommendation is that women with IBD on any monoclonal antibodies, including newer interleukin-23s, may breastfeed even though there are not clinical trial data at this point. The recommendation to continue them through pregnancy and lactation is based on placental physiology, as well as on the physiology of monoclonal antibody transfer in breast milk, according to the consortium.

Furthermore, the authors noted, there was no increase in infant infections at 4 months or 12 months if they were exposed to a biologic or thiopurine (or both) during pregnancy.

Overall, the consortium recommended that all pregnancies for women with IBD be considered as “high risk” for complications. This is due to the fact that many parts of the world, including the US, are “resource-limited,” Mahadevan explained. Since maternal fetal medicine specialists are not widely available, the consortium suggested all these patients be followed with increased monitoring and surveillance based on available resources.

In addition to the guidelines, patient videos in seven languages, a professional slide deck in English and Spanish, and a video on the global consensus are all available at https://pianostudy.org/.

This study was funded by The Leona B. and Harry H. Helmsley Charitable Trust.

Mahadevan reported being a consultant for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Merck, Pfizer, Protagonist, Roivant, and Takeda.

A version of this article appeared on Medscape.com. 

The first-ever global guidelines for pregnancy and inflammatory bowel disease (IBD) recommend continuing biologics and low-risk medications through pregnancy and lactation in women with IBD, suggesting this approach will not harm the fetus.

The guidelines also recommend that all women with IBD receive preconception counseling and be followed as high-risk pregnancies.

“Management of chronic illness in pregnant women has always been defined by fear of harming the fetus,” said Uma Mahadevan, MD, AGAF, director of the Colitis and Crohn’s Disease Center at the University of California San Francisco and chair of the Global Consensus Consortium that developed the guidelines. 

As a result, pregnant women are excluded from clinical trials of experimental therapies for IBD. And when a new therapy achieves regulatory approval, there are no human pregnancy safety data, only animal data. To fill this gap, the PIANO study, of which Mahadevan is principal investigator, looked at the safety of IBD medications in pregnancy and short- and long-term outcomes of the children.

“With our ongoing work in pregnancy in the patient with IBD, we realized that inflammation in the mother is the leading cause of poor outcome for the infant,” she told GI & Hepatology News. 

“We also have a better understanding of placental transfer of biologic agents” and the lack of exposure to the fetus during the first trimester, “a key period of organogenesis,” she added. 

Final recommendations were published simultaneously in six international journals, namely, Clinical Gastroenterology and Hepatology, American Journal of Gastroenterology, GUT, Inflammatory Bowel Diseases, Journal of Crohn’s and Colitis, and Alimentary Pharmacology and Therapeutics.

 

Surprising, Novel Findings

Limited provider knowledge led to varied practices in caring for women with IBD who become pregnant, according to the consensus authors. Practices are affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus. 

“The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike,” the authors of the guidelines wrote. 

Therefore, the Global Consensus Consortium — a group of 39 IBD experts, including teratologists and maternal fetal medicine specialists and seven patient advocates from six continents — convened to review and assess current data and come to an agreement on best practices. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used when sufficient published data were available, and the Research and Development process when expert opinion was needed to guide consistent practice.

“Some of the findings were expected, but others were novel,” said Mahadevan. 

Recommendations that might surprise clinicians include GRADE statement 9, which suggests that pregnant women with IBD take low-dose aspirin by 12 to 16 weeks’ gestation to prevent preterm preeclampsia. “This is based on the ASPRE study, showing that women at risk of preeclampsia can lower their risk by taking low-dose aspirin,” with no risk for flare, Mahadevan said.

In addition, GRADE statements 17-20 recommend/suggest that women continue their biologic throughout pregnancy without stopping. “North America has always recommended continuing during the third trimester, while Europe only recently has come to this,” Mahadevan said. “However, there was always some looseness about stopping at week X, Y, or Z. Now, we do recommend continuing the dose on schedule with no holding.”

Continuing medications considered low risk for use during pregnancy, such as 5-amino salicylic acids, sulfasalazine, thiopurines, and all monoclonal antibodies during preconception, pregnancy, and lactation, was also recommended. 

However, small-molecule drugs such as S1P receptor molecules and JAK inhibitors should be avoided for at least 1 month, and in some cases for 3 months prior to attempting conception, unless there is no alternative for the health of the mother. They should also be avoided during lactation.

Grade statement 33, which suggests that live rotavirus vaccine may be provided in children with in utero exposure to biologics, is also new, Mahadevan noted. “All prior recommendations were that no live vaccine should be given in the first 6 months or longer if infants were exposed to biologics in utero, but based on a prospective Canadian study, there is no harm when given to these infants.”

Another novel recommendation is that women with IBD on any monoclonal antibodies, including newer interleukin-23s, may breastfeed even though there are not clinical trial data at this point. The recommendation to continue them through pregnancy and lactation is based on placental physiology, as well as on the physiology of monoclonal antibody transfer in breast milk, according to the consortium.

Furthermore, the authors noted, there was no increase in infant infections at 4 months or 12 months if they were exposed to a biologic or thiopurine (or both) during pregnancy.

Overall, the consortium recommended that all pregnancies for women with IBD be considered as “high risk” for complications. This is due to the fact that many parts of the world, including the US, are “resource-limited,” Mahadevan explained. Since maternal fetal medicine specialists are not widely available, the consortium suggested all these patients be followed with increased monitoring and surveillance based on available resources.

In addition to the guidelines, patient videos in seven languages, a professional slide deck in English and Spanish, and a video on the global consensus are all available at https://pianostudy.org/.

This study was funded by The Leona B. and Harry H. Helmsley Charitable Trust.

Mahadevan reported being a consultant for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Merck, Pfizer, Protagonist, Roivant, and Takeda.

A version of this article appeared on Medscape.com. 

Patients with intestinal methanogen overgrowth (IMO) have a higher rate and severity of constipation but a lower rate and severity of diarrhea, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.

“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care. 

Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation. 

 

The Study

To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.

Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6. 

Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).

In other findings:

• Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
• They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
• Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
• Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.

Mechanism of Action

The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.

Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.

“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.

This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.

Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.

Patients with intestinal methanogen overgrowth (IMO) have a higher rate and severity of constipation but a lower rate and severity of diarrhea, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.

“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care. 

Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation. 

 

The Study

To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.

Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6. 

Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).

In other findings:

• Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
• They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
• Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
• Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.

Mechanism of Action

The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.

Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.

“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.

This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.

Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.

Patients with intestinal methanogen overgrowth (IMO) have a higher rate and severity of constipation but a lower rate and severity of diarrhea, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.

“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care. 

Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation. 

 

The Study

To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.

Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6. 

Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).

In other findings:

• Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
• They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
• Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
• Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.

Mechanism of Action

The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.

Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.

“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.

This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.

Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.

An increase of patients presenting with the complex combination of hypermobile Ehlers-Danlos syndrome (hEDS) with co-existing gastrointestinal (GI) symptoms, postural orthostatic tachycardia syndrome (POTS), and/or mast cell activation syndrome (MCAS), has prompted the issuance of clinical practice guidance from AGA to help clinicians comprehend such cases.

“Recognizing and treating GI symptoms in patients with hEDS or hypermobility spectrum disorders and comorbid POTS or MCAS present major challenges for clinicians, who often feel under equipped to address their needs,” AGA reported in the update, published in Clinical Gastroenterology and Hepatology.

Importantly, “the poor understanding of these overlapping syndromes can lead to nonstandardized approaches to diagnostic evaluation and management,” the authors noted.

“Gastroenterology providers should be aware of the features of [these syndromes] to recognize the full complexity of patients presenting with multisystemic symptoms.”

Hypermobility spectrum disorders, which include hEDS, are typically genetic, and patients experience pain along with joint hypermobility, or extreme flexibility of joints beyond the normal range of motion.

With research showing that most of those patients — up to 98% — also experience GI symptoms, gastroenterologists may be encountering them more commonly than realized, Lucinda A. Harris, MD, AGAF, of the Mayo Clinic School of Medicine, in Scottsdale, Arizona, explained to GI & Hepatology News.

“As our knowledge in gastroenterology has progressed, we realize that hypermobility itself predisposes individuals to disorders of brain-gut interaction,” she said. “We may only be seeing the tip of the iceberg when it comes to diagnosing patients with hypermobility.”

Additionally, “many of these patients have POTS, which has also been increasingly diagnosed,” Harris added. “The strong overlap of these conditions prompted us to present this data.”

With a lack of evidence-based understanding of the overlapping syndromes, AGA’s guidance does not carry formal ratings but is drawn from a review of the published literature and expert opinion.

In addition to the key recommendation of being aware of the observed combination of syndromes, their recommendations include:

• Regarding testing: Testing for POTS/MCAS should be targeted to patients presenting with clinical manifestations of the disorders, but universal testing for POTS/MCAS in all patients with hEDS or hypermobility spectrum disorders is not currently supported by the evidence, the guidance advises.
• Gastroenterologists seeing patients with disorders of gut-brain interaction should inquire about joint hypermobility and strongly consider incorporating the Beighton score for assessing joint hypermobility into their practice as a screening tool; if the screen is positive, gastroenterologists may consider applying 2017 diagnostic criteria to diagnose hEDS or offer appropriate referral to a specialist where resources are available, the AGA recommends.
• Medical management: Management of GI symptoms in hEDS or hypermobility spectrum disorders and POTS/MCAS should focus on treating the most prominent GI symptoms and abnormal GI function test results.
• In addition to general disorders of gut-brain interactions and GI motility disorder treatment, management should also include treating any symptoms attributable to POTS and/or MCAS.

Treatment of POTS may include increasing fluid and salt intake, exercise training, and use of compression garments. Special pharmacological treatments for volume expansion, heart rate control, and vasoconstriction with integrated care from multiple specialties (eg, cardiology, neurology) should be considered in patients who do not respond to conservative lifestyle measures.

In patients presenting to gastroenterology providers, testing for mast cell disorders including MCAS should be considered in patients with hEDS or hypermobility spectrum disorders and disorders of gut-brain interaction with episodic symptoms that suggest a more generalized mast cell disorder involving two or more physiological systems. However, current data does not support the use of these tests for routine evaluation of GI symptoms in all patients with hEDS or hypermobility spectrum disorders without clinical or laboratory evidence of a primary or secondary mast cell disorder, the authors noted.

Harris explained that patients presenting with gut-brain disorders are often mistakenly classified as having irritable bowel syndrome or dyspepsia, whereas these conditions may be affecting the GI disorders they have.

“For example, a patient with Ehlers-Danlos syndrome might have problems with constipation, which is impacted by pelvic floor dysfunction,” she said. “Due to their hypermobility, they may experience more pelvic floor descent than usual.”

“If we do not recognize this, the patient risks developing rectal prolapse or not effectively addressing their constipation.”

Regarding patient characteristics, Harris said that those with hEDS and POTS appear to more likely be women and tend to present in younger patients, aged 18-50 years. Of note, there is no genetic test for hEDS.

“The take-home point for clinicians should be to consider POTS and Ehlers-Danlos syndrome when encountering young female patients with symptoms of palpitations, hypermobility, and orthostatic intolerance,” she said.

“Recognizing hypermobility is crucial, not only for GI symptoms but also to prevent joint dislocations, tendon ruptures, and other connective tissue issues.”

Clinicians are further urged to “offer informed counseling, and guide patients away from unreliable sources or fragmented care to foster therapeutic relationships and evidence-based care,” the authors added.

 

Deciphering Gut-Brain Disorder Challenges

Commenting to GI & Hepatology News, Clair Francomano, MD, a professor of medical and molecular genetics at the Indiana University School of Medicine, in Indianapolis, said the new guidance sheds important light on the syndromes.

“I’m delighted to see this guidance offered through the AGA as it will encourage gastroenterologists to think of EDS, POTS and MCAS when they are evaluating patients with disorders of gut-brain interaction,” Francomano said.

“This should allow patients to receive more accurate and timely diagnoses and appropriate management.”

Francomano noted that the Ehlers-Danlos Society, which provides information for clinicians and patients alike on the syndromes, and where she serves on the medical scientific board, has also been active in raising awareness.

“While co-occurrence of POTS and MCAS with EDS has in fact been recognized for many years, I do think awareness is increasing, in large part due to the advocacy and educational efforts of the Ehlers-Danlos Society,” she said.

The take-home message? “When clinicians see disorders of the gut-brain axis, POTS or MCAS, they should be thinking, ‘Could this be related to joint hypermobility or Ehlers-Danlos syndrome?’” Francomano said.

Harris reported serving as a consultant for AbbVie, Ardelyx, Salix, and Gemelli Biotech and reported receiving research support from Takeda and Anyx. Francomano did not report any relevant disclosures.

A version of this article appeared on Medscape.com.

An increase of patients presenting with the complex combination of hypermobile Ehlers-Danlos syndrome (hEDS) with co-existing gastrointestinal (GI) symptoms, postural orthostatic tachycardia syndrome (POTS), and/or mast cell activation syndrome (MCAS), has prompted the issuance of clinical practice guidance from AGA to help clinicians comprehend such cases.

“Recognizing and treating GI symptoms in patients with hEDS or hypermobility spectrum disorders and comorbid POTS or MCAS present major challenges for clinicians, who often feel under equipped to address their needs,” AGA reported in the update, published in Clinical Gastroenterology and Hepatology.

Importantly, “the poor understanding of these overlapping syndromes can lead to nonstandardized approaches to diagnostic evaluation and management,” the authors noted.

“Gastroenterology providers should be aware of the features of [these syndromes] to recognize the full complexity of patients presenting with multisystemic symptoms.”

Hypermobility spectrum disorders, which include hEDS, are typically genetic, and patients experience pain along with joint hypermobility, or extreme flexibility of joints beyond the normal range of motion.

With research showing that most of those patients — up to 98% — also experience GI symptoms, gastroenterologists may be encountering them more commonly than realized, Lucinda A. Harris, MD, AGAF, of the Mayo Clinic School of Medicine, in Scottsdale, Arizona, explained to GI & Hepatology News.

“As our knowledge in gastroenterology has progressed, we realize that hypermobility itself predisposes individuals to disorders of brain-gut interaction,” she said. “We may only be seeing the tip of the iceberg when it comes to diagnosing patients with hypermobility.”

Additionally, “many of these patients have POTS, which has also been increasingly diagnosed,” Harris added. “The strong overlap of these conditions prompted us to present this data.”

With a lack of evidence-based understanding of the overlapping syndromes, AGA’s guidance does not carry formal ratings but is drawn from a review of the published literature and expert opinion.

In addition to the key recommendation of being aware of the observed combination of syndromes, their recommendations include:

• Regarding testing: Testing for POTS/MCAS should be targeted to patients presenting with clinical manifestations of the disorders, but universal testing for POTS/MCAS in all patients with hEDS or hypermobility spectrum disorders is not currently supported by the evidence, the guidance advises.
• Gastroenterologists seeing patients with disorders of gut-brain interaction should inquire about joint hypermobility and strongly consider incorporating the Beighton score for assessing joint hypermobility into their practice as a screening tool; if the screen is positive, gastroenterologists may consider applying 2017 diagnostic criteria to diagnose hEDS or offer appropriate referral to a specialist where resources are available, the AGA recommends.
• Medical management: Management of GI symptoms in hEDS or hypermobility spectrum disorders and POTS/MCAS should focus on treating the most prominent GI symptoms and abnormal GI function test results.
• In addition to general disorders of gut-brain interactions and GI motility disorder treatment, management should also include treating any symptoms attributable to POTS and/or MCAS.

Treatment of POTS may include increasing fluid and salt intake, exercise training, and use of compression garments. Special pharmacological treatments for volume expansion, heart rate control, and vasoconstriction with integrated care from multiple specialties (eg, cardiology, neurology) should be considered in patients who do not respond to conservative lifestyle measures.

In patients presenting to gastroenterology providers, testing for mast cell disorders including MCAS should be considered in patients with hEDS or hypermobility spectrum disorders and disorders of gut-brain interaction with episodic symptoms that suggest a more generalized mast cell disorder involving two or more physiological systems. However, current data does not support the use of these tests for routine evaluation of GI symptoms in all patients with hEDS or hypermobility spectrum disorders without clinical or laboratory evidence of a primary or secondary mast cell disorder, the authors noted.

Harris explained that patients presenting with gut-brain disorders are often mistakenly classified as having irritable bowel syndrome or dyspepsia, whereas these conditions may be affecting the GI disorders they have.

“For example, a patient with Ehlers-Danlos syndrome might have problems with constipation, which is impacted by pelvic floor dysfunction,” she said. “Due to their hypermobility, they may experience more pelvic floor descent than usual.”

“If we do not recognize this, the patient risks developing rectal prolapse or not effectively addressing their constipation.”

Regarding patient characteristics, Harris said that those with hEDS and POTS appear to more likely be women and tend to present in younger patients, aged 18-50 years. Of note, there is no genetic test for hEDS.

“The take-home point for clinicians should be to consider POTS and Ehlers-Danlos syndrome when encountering young female patients with symptoms of palpitations, hypermobility, and orthostatic intolerance,” she said.

“Recognizing hypermobility is crucial, not only for GI symptoms but also to prevent joint dislocations, tendon ruptures, and other connective tissue issues.”

Clinicians are further urged to “offer informed counseling, and guide patients away from unreliable sources or fragmented care to foster therapeutic relationships and evidence-based care,” the authors added.

 

Deciphering Gut-Brain Disorder Challenges

Commenting to GI & Hepatology News, Clair Francomano, MD, a professor of medical and molecular genetics at the Indiana University School of Medicine, in Indianapolis, said the new guidance sheds important light on the syndromes.

“I’m delighted to see this guidance offered through the AGA as it will encourage gastroenterologists to think of EDS, POTS and MCAS when they are evaluating patients with disorders of gut-brain interaction,” Francomano said.

“This should allow patients to receive more accurate and timely diagnoses and appropriate management.”

Francomano noted that the Ehlers-Danlos Society, which provides information for clinicians and patients alike on the syndromes, and where she serves on the medical scientific board, has also been active in raising awareness.

“While co-occurrence of POTS and MCAS with EDS has in fact been recognized for many years, I do think awareness is increasing, in large part due to the advocacy and educational efforts of the Ehlers-Danlos Society,” she said.

The take-home message? “When clinicians see disorders of the gut-brain axis, POTS or MCAS, they should be thinking, ‘Could this be related to joint hypermobility or Ehlers-Danlos syndrome?’” Francomano said.

Harris reported serving as a consultant for AbbVie, Ardelyx, Salix, and Gemelli Biotech and reported receiving research support from Takeda and Anyx. Francomano did not report any relevant disclosures.

A version of this article appeared on Medscape.com.

An increase of patients presenting with the complex combination of hypermobile Ehlers-Danlos syndrome (hEDS) with co-existing gastrointestinal (GI) symptoms, postural orthostatic tachycardia syndrome (POTS), and/or mast cell activation syndrome (MCAS), has prompted the issuance of clinical practice guidance from AGA to help clinicians comprehend such cases.

“Recognizing and treating GI symptoms in patients with hEDS or hypermobility spectrum disorders and comorbid POTS or MCAS present major challenges for clinicians, who often feel under equipped to address their needs,” AGA reported in the update, published in Clinical Gastroenterology and Hepatology.

Importantly, “the poor understanding of these overlapping syndromes can lead to nonstandardized approaches to diagnostic evaluation and management,” the authors noted.

“Gastroenterology providers should be aware of the features of [these syndromes] to recognize the full complexity of patients presenting with multisystemic symptoms.”

Hypermobility spectrum disorders, which include hEDS, are typically genetic, and patients experience pain along with joint hypermobility, or extreme flexibility of joints beyond the normal range of motion.

With research showing that most of those patients — up to 98% — also experience GI symptoms, gastroenterologists may be encountering them more commonly than realized, Lucinda A. Harris, MD, AGAF, of the Mayo Clinic School of Medicine, in Scottsdale, Arizona, explained to GI & Hepatology News.

“As our knowledge in gastroenterology has progressed, we realize that hypermobility itself predisposes individuals to disorders of brain-gut interaction,” she said. “We may only be seeing the tip of the iceberg when it comes to diagnosing patients with hypermobility.”

Additionally, “many of these patients have POTS, which has also been increasingly diagnosed,” Harris added. “The strong overlap of these conditions prompted us to present this data.”

With a lack of evidence-based understanding of the overlapping syndromes, AGA’s guidance does not carry formal ratings but is drawn from a review of the published literature and expert opinion.

In addition to the key recommendation of being aware of the observed combination of syndromes, their recommendations include:

• Regarding testing: Testing for POTS/MCAS should be targeted to patients presenting with clinical manifestations of the disorders, but universal testing for POTS/MCAS in all patients with hEDS or hypermobility spectrum disorders is not currently supported by the evidence, the guidance advises.
• Gastroenterologists seeing patients with disorders of gut-brain interaction should inquire about joint hypermobility and strongly consider incorporating the Beighton score for assessing joint hypermobility into their practice as a screening tool; if the screen is positive, gastroenterologists may consider applying 2017 diagnostic criteria to diagnose hEDS or offer appropriate referral to a specialist where resources are available, the AGA recommends.
• Medical management: Management of GI symptoms in hEDS or hypermobility spectrum disorders and POTS/MCAS should focus on treating the most prominent GI symptoms and abnormal GI function test results.
• In addition to general disorders of gut-brain interactions and GI motility disorder treatment, management should also include treating any symptoms attributable to POTS and/or MCAS.

Treatment of POTS may include increasing fluid and salt intake, exercise training, and use of compression garments. Special pharmacological treatments for volume expansion, heart rate control, and vasoconstriction with integrated care from multiple specialties (eg, cardiology, neurology) should be considered in patients who do not respond to conservative lifestyle measures.

In patients presenting to gastroenterology providers, testing for mast cell disorders including MCAS should be considered in patients with hEDS or hypermobility spectrum disorders and disorders of gut-brain interaction with episodic symptoms that suggest a more generalized mast cell disorder involving two or more physiological systems. However, current data does not support the use of these tests for routine evaluation of GI symptoms in all patients with hEDS or hypermobility spectrum disorders without clinical or laboratory evidence of a primary or secondary mast cell disorder, the authors noted.

Harris explained that patients presenting with gut-brain disorders are often mistakenly classified as having irritable bowel syndrome or dyspepsia, whereas these conditions may be affecting the GI disorders they have.

“For example, a patient with Ehlers-Danlos syndrome might have problems with constipation, which is impacted by pelvic floor dysfunction,” she said. “Due to their hypermobility, they may experience more pelvic floor descent than usual.”

“If we do not recognize this, the patient risks developing rectal prolapse or not effectively addressing their constipation.”

Regarding patient characteristics, Harris said that those with hEDS and POTS appear to more likely be women and tend to present in younger patients, aged 18-50 years. Of note, there is no genetic test for hEDS.

“The take-home point for clinicians should be to consider POTS and Ehlers-Danlos syndrome when encountering young female patients with symptoms of palpitations, hypermobility, and orthostatic intolerance,” she said.

“Recognizing hypermobility is crucial, not only for GI symptoms but also to prevent joint dislocations, tendon ruptures, and other connective tissue issues.”

Clinicians are further urged to “offer informed counseling, and guide patients away from unreliable sources or fragmented care to foster therapeutic relationships and evidence-based care,” the authors added.

 

Deciphering Gut-Brain Disorder Challenges

Commenting to GI & Hepatology News, Clair Francomano, MD, a professor of medical and molecular genetics at the Indiana University School of Medicine, in Indianapolis, said the new guidance sheds important light on the syndromes.

“I’m delighted to see this guidance offered through the AGA as it will encourage gastroenterologists to think of EDS, POTS and MCAS when they are evaluating patients with disorders of gut-brain interaction,” Francomano said.

“This should allow patients to receive more accurate and timely diagnoses and appropriate management.”

Francomano noted that the Ehlers-Danlos Society, which provides information for clinicians and patients alike on the syndromes, and where she serves on the medical scientific board, has also been active in raising awareness.

“While co-occurrence of POTS and MCAS with EDS has in fact been recognized for many years, I do think awareness is increasing, in large part due to the advocacy and educational efforts of the Ehlers-Danlos Society,” she said.

The take-home message? “When clinicians see disorders of the gut-brain axis, POTS or MCAS, they should be thinking, ‘Could this be related to joint hypermobility or Ehlers-Danlos syndrome?’” Francomano said.

Harris reported serving as a consultant for AbbVie, Ardelyx, Salix, and Gemelli Biotech and reported receiving research support from Takeda and Anyx. Francomano did not report any relevant disclosures.

A version of this article appeared on Medscape.com.

Out-of-pocket costs for bowel preparation are deterring people, especially vulnerable and underserved groups, from colonoscopy for colorectal cancer (CRC) screening, a large insurance-claims analysis in Gastroenterology reported.

Moreover, this cost-sharing contravenes the preventive-care provisions for bowel preparation mandated by the Affordable Care Act (ACA).

Led by Gastroenterologist Eric D. Shah, MD, MBA, a clinical associate professor at the University of Michigan in Ann Arbor, Michigan, the study found a significant proportion of prescribed bowel preparation claims — 53% for commercial plans and 83% for Medicare — still involve patient cost-sharing, indicating noncompliance with ACA guidelines. Although expense-sharing was less prevalent among Medicaid claims (just 27%), it was not eliminated, suggesting room for improvement in coverage enforcement across the board.

“Colon cancer is unique in that it can be prevented with colonoscopy, but where are the patients? Bowel prep is a major reason that patients defer screening,” Shah told GI & Hepatology News. He said his group was quite surprised that the majority in the study cohort were paying something out of pocket when these costs should have been covered. “Primary care doctors may not think to ask about bowel prep costs when they order screening colonoscopies.”

The findings emerged from an analysis of 2,593,079 prescription drug claims: 52.9% from commercial plans, 35% from Medicare Part D plans, and 8.3% from Medicaid plans.

“These patient costs of $30 or $50 are a real not a theoretical deterrent,” said Whitney Jones, MD, a gastroenterologist, adjunct clinical professor at the University of Louisville in Louisville, Kentucky, and founder of the nonprofit Colon Cancer Prevention Project. Jones was not involved in the analysis. “Some insurers require prior patient authorization for the low-dose preps, but gastroenterologists are doing so many colonoscopies they don’t always have time to get a PA [prior authorization] on everyone.” 

With the increasing use of blood and stool-based CRC testing, he added, “when you get a positive result, it’s really important to have the procedure quickly.” And appropriate bowel preparation is a small, cost-effective portion of the total costs of colonoscopy, a procedure that ultimately saves insurers significant money in treatment costs.

The authors noted that while CRC is the second-leading cause of cancer-related deaths in the US, screening rates remain low, with only 59% of adults aged 45 years or older up to date with screening. Screening rates are particularly low among racial and ethnic minority groups as compared with White individuals, a disparity that highlights the need to address existing barriers and enhance screening efforts.

In the current study, shared costs by bowel preparation volume also varied. Low-volume formulations had consistently higher out-of-pocket costs: a median of $60 for low-volume vs $10 for high-volume in commercial plans. In Medicare, 75% of high-volume claims had shared costs compared with 90% for their low-volume counterparts. The cost-sharing difference was slightly narrower with Medicaid: 27% of high-volume claims vs 30% of low-volume claims.

This is concerning, as low-volume options, which are preferred by patients for their better tolerability, can enhance uptake and adherence and improve colonoscopy outcomes. Shah advises physicians to consider prescribing low-volume preparations. “Let patients know about the potential out-of-pocket cost and about copay cards and assistance programs and use high-volume preps as an alternative rather than a go-to,” he said.

As to costs across insurance types, among commercial plans, the median nonzero out-of-pocket cost was $10 for high-volume and $60 for low-volume product claims. For Medicare, the median nonzero out-of-pocket cost was $8 for high-volume and $55.99 for low-volume products.

Under the ACA, CRC screening is classified as a recommended preventive service, requiring health plans to cover it without cost-sharing. Although the Centers for Medicare & Medicaid Services previously tried to enforce this mandate in 2015 and 2016, stating that colonoscopy preparation medications should be covered at no cost, many health plans are still not compliant.

At the nonfederal level, Jones noted, Kentucky, which has a significant high-risk population, recently became the first state to pass legislation requiring health benefit plans to cover all guideline-recommended CRC exams and lab tests.

For its part, AGA has also called on payers to eliminate all cost-sharing barriers across the CRC screening continuum.

Of note, the study authors said, the higher compliance with the ACA mandate in commercial and Medicaid plans than in Medicare highlights disparities that may disproportionately affect vulnerable older adults. While nearly half of commercial patients and nearly three quarters of Medicaid patients incurred zero out-of-pocket costs, fewer than 17% of Medicare beneficiaries, or 1 in 6, did so.

Although these costs may be low relative to the colonoscopy, they nevertheless can deter uptake of preventive screenings, potentially leading to higher CRC incidence and mortality. “While some patients may be willing to pay modest out-of-pocket costs, any required payment, however small, can serve as a barrier to preventative care, particularly in underserved populations,” they wrote. “These financial barriers will continue to contribute to widening disparities and hinder progress toward equitable screening outcomes.”

In the meantime, said Shah, “Physicians should advocate now to their representatives in Congress that bowel prep costs should already be covered as part of the ACA.”

This study was funded by Sebela Pharmaceuticals, maker of SUFLAVE preparation. The authors had no conflicts of interest to declare. Jones is a speaker and consultant for Grail LLC.

A version of this article appeared on Medscape.com.

Out-of-pocket costs for bowel preparation are deterring people, especially vulnerable and underserved groups, from colonoscopy for colorectal cancer (CRC) screening, a large insurance-claims analysis in Gastroenterology reported.

Moreover, this cost-sharing contravenes the preventive-care provisions for bowel preparation mandated by the Affordable Care Act (ACA).

Led by Gastroenterologist Eric D. Shah, MD, MBA, a clinical associate professor at the University of Michigan in Ann Arbor, Michigan, the study found a significant proportion of prescribed bowel preparation claims — 53% for commercial plans and 83% for Medicare — still involve patient cost-sharing, indicating noncompliance with ACA guidelines. Although expense-sharing was less prevalent among Medicaid claims (just 27%), it was not eliminated, suggesting room for improvement in coverage enforcement across the board.

“Colon cancer is unique in that it can be prevented with colonoscopy, but where are the patients? Bowel prep is a major reason that patients defer screening,” Shah told GI & Hepatology News. He said his group was quite surprised that the majority in the study cohort were paying something out of pocket when these costs should have been covered. “Primary care doctors may not think to ask about bowel prep costs when they order screening colonoscopies.”

The findings emerged from an analysis of 2,593,079 prescription drug claims: 52.9% from commercial plans, 35% from Medicare Part D plans, and 8.3% from Medicaid plans.

“These patient costs of $30 or $50 are a real not a theoretical deterrent,” said Whitney Jones, MD, a gastroenterologist, adjunct clinical professor at the University of Louisville in Louisville, Kentucky, and founder of the nonprofit Colon Cancer Prevention Project. Jones was not involved in the analysis. “Some insurers require prior patient authorization for the low-dose preps, but gastroenterologists are doing so many colonoscopies they don’t always have time to get a PA [prior authorization] on everyone.” 

With the increasing use of blood and stool-based CRC testing, he added, “when you get a positive result, it’s really important to have the procedure quickly.” And appropriate bowel preparation is a small, cost-effective portion of the total costs of colonoscopy, a procedure that ultimately saves insurers significant money in treatment costs.

The authors noted that while CRC is the second-leading cause of cancer-related deaths in the US, screening rates remain low, with only 59% of adults aged 45 years or older up to date with screening. Screening rates are particularly low among racial and ethnic minority groups as compared with White individuals, a disparity that highlights the need to address existing barriers and enhance screening efforts.

In the current study, shared costs by bowel preparation volume also varied. Low-volume formulations had consistently higher out-of-pocket costs: a median of $60 for low-volume vs $10 for high-volume in commercial plans. In Medicare, 75% of high-volume claims had shared costs compared with 90% for their low-volume counterparts. The cost-sharing difference was slightly narrower with Medicaid: 27% of high-volume claims vs 30% of low-volume claims.

This is concerning, as low-volume options, which are preferred by patients for their better tolerability, can enhance uptake and adherence and improve colonoscopy outcomes. Shah advises physicians to consider prescribing low-volume preparations. “Let patients know about the potential out-of-pocket cost and about copay cards and assistance programs and use high-volume preps as an alternative rather than a go-to,” he said.

As to costs across insurance types, among commercial plans, the median nonzero out-of-pocket cost was $10 for high-volume and $60 for low-volume product claims. For Medicare, the median nonzero out-of-pocket cost was $8 for high-volume and $55.99 for low-volume products.

Under the ACA, CRC screening is classified as a recommended preventive service, requiring health plans to cover it without cost-sharing. Although the Centers for Medicare & Medicaid Services previously tried to enforce this mandate in 2015 and 2016, stating that colonoscopy preparation medications should be covered at no cost, many health plans are still not compliant.

At the nonfederal level, Jones noted, Kentucky, which has a significant high-risk population, recently became the first state to pass legislation requiring health benefit plans to cover all guideline-recommended CRC exams and lab tests.

For its part, AGA has also called on payers to eliminate all cost-sharing barriers across the CRC screening continuum.

Of note, the study authors said, the higher compliance with the ACA mandate in commercial and Medicaid plans than in Medicare highlights disparities that may disproportionately affect vulnerable older adults. While nearly half of commercial patients and nearly three quarters of Medicaid patients incurred zero out-of-pocket costs, fewer than 17% of Medicare beneficiaries, or 1 in 6, did so.

Although these costs may be low relative to the colonoscopy, they nevertheless can deter uptake of preventive screenings, potentially leading to higher CRC incidence and mortality. “While some patients may be willing to pay modest out-of-pocket costs, any required payment, however small, can serve as a barrier to preventative care, particularly in underserved populations,” they wrote. “These financial barriers will continue to contribute to widening disparities and hinder progress toward equitable screening outcomes.”

In the meantime, said Shah, “Physicians should advocate now to their representatives in Congress that bowel prep costs should already be covered as part of the ACA.”

This study was funded by Sebela Pharmaceuticals, maker of SUFLAVE preparation. The authors had no conflicts of interest to declare. Jones is a speaker and consultant for Grail LLC.

A version of this article appeared on Medscape.com.

Out-of-pocket costs for bowel preparation are deterring people, especially vulnerable and underserved groups, from colonoscopy for colorectal cancer (CRC) screening, a large insurance-claims analysis in Gastroenterology reported.

Moreover, this cost-sharing contravenes the preventive-care provisions for bowel preparation mandated by the Affordable Care Act (ACA).

Led by Gastroenterologist Eric D. Shah, MD, MBA, a clinical associate professor at the University of Michigan in Ann Arbor, Michigan, the study found a significant proportion of prescribed bowel preparation claims — 53% for commercial plans and 83% for Medicare — still involve patient cost-sharing, indicating noncompliance with ACA guidelines. Although expense-sharing was less prevalent among Medicaid claims (just 27%), it was not eliminated, suggesting room for improvement in coverage enforcement across the board.

“Colon cancer is unique in that it can be prevented with colonoscopy, but where are the patients? Bowel prep is a major reason that patients defer screening,” Shah told GI & Hepatology News. He said his group was quite surprised that the majority in the study cohort were paying something out of pocket when these costs should have been covered. “Primary care doctors may not think to ask about bowel prep costs when they order screening colonoscopies.”

The findings emerged from an analysis of 2,593,079 prescription drug claims: 52.9% from commercial plans, 35% from Medicare Part D plans, and 8.3% from Medicaid plans.

“These patient costs of $30 or $50 are a real not a theoretical deterrent,” said Whitney Jones, MD, a gastroenterologist, adjunct clinical professor at the University of Louisville in Louisville, Kentucky, and founder of the nonprofit Colon Cancer Prevention Project. Jones was not involved in the analysis. “Some insurers require prior patient authorization for the low-dose preps, but gastroenterologists are doing so many colonoscopies they don’t always have time to get a PA [prior authorization] on everyone.” 

With the increasing use of blood and stool-based CRC testing, he added, “when you get a positive result, it’s really important to have the procedure quickly.” And appropriate bowel preparation is a small, cost-effective portion of the total costs of colonoscopy, a procedure that ultimately saves insurers significant money in treatment costs.

The authors noted that while CRC is the second-leading cause of cancer-related deaths in the US, screening rates remain low, with only 59% of adults aged 45 years or older up to date with screening. Screening rates are particularly low among racial and ethnic minority groups as compared with White individuals, a disparity that highlights the need to address existing barriers and enhance screening efforts.

In the current study, shared costs by bowel preparation volume also varied. Low-volume formulations had consistently higher out-of-pocket costs: a median of $60 for low-volume vs $10 for high-volume in commercial plans. In Medicare, 75% of high-volume claims had shared costs compared with 90% for their low-volume counterparts. The cost-sharing difference was slightly narrower with Medicaid: 27% of high-volume claims vs 30% of low-volume claims.

This is concerning, as low-volume options, which are preferred by patients for their better tolerability, can enhance uptake and adherence and improve colonoscopy outcomes. Shah advises physicians to consider prescribing low-volume preparations. “Let patients know about the potential out-of-pocket cost and about copay cards and assistance programs and use high-volume preps as an alternative rather than a go-to,” he said.

As to costs across insurance types, among commercial plans, the median nonzero out-of-pocket cost was $10 for high-volume and $60 for low-volume product claims. For Medicare, the median nonzero out-of-pocket cost was $8 for high-volume and $55.99 for low-volume products.

Under the ACA, CRC screening is classified as a recommended preventive service, requiring health plans to cover it without cost-sharing. Although the Centers for Medicare & Medicaid Services previously tried to enforce this mandate in 2015 and 2016, stating that colonoscopy preparation medications should be covered at no cost, many health plans are still not compliant.

At the nonfederal level, Jones noted, Kentucky, which has a significant high-risk population, recently became the first state to pass legislation requiring health benefit plans to cover all guideline-recommended CRC exams and lab tests.

For its part, AGA has also called on payers to eliminate all cost-sharing barriers across the CRC screening continuum.

Of note, the study authors said, the higher compliance with the ACA mandate in commercial and Medicaid plans than in Medicare highlights disparities that may disproportionately affect vulnerable older adults. While nearly half of commercial patients and nearly three quarters of Medicaid patients incurred zero out-of-pocket costs, fewer than 17% of Medicare beneficiaries, or 1 in 6, did so.

Although these costs may be low relative to the colonoscopy, they nevertheless can deter uptake of preventive screenings, potentially leading to higher CRC incidence and mortality. “While some patients may be willing to pay modest out-of-pocket costs, any required payment, however small, can serve as a barrier to preventative care, particularly in underserved populations,” they wrote. “These financial barriers will continue to contribute to widening disparities and hinder progress toward equitable screening outcomes.”

In the meantime, said Shah, “Physicians should advocate now to their representatives in Congress that bowel prep costs should already be covered as part of the ACA.”

This study was funded by Sebela Pharmaceuticals, maker of SUFLAVE preparation. The authors had no conflicts of interest to declare. Jones is a speaker and consultant for Grail LLC.

A version of this article appeared on Medscape.com.

Most GI service chiefs in the U.S. Veterans Affairs (VA) healthcare system support point-of-care ultrasound (POCUS) training, but fewer than half have the technology in their facility, according to a national survey.

Low POCUS uptake may be explained by substantial barriers to implementation, including lack of trained instructors, necessary equipment, and support staff, lead author Keerthi Thallapureddy, MD, of the University of Texas Health San Antonio, and colleagues, reported.

“POCUS is being increasingly used by gastroenterologists due to its portability and real-time diagnostic ability,” the investigators wrote in Gastro Hep Advances, but “there is limited understanding of how gastroenterologists use POCUS.”

To learn more, the investigators conducted a nationwide survey of the VA healthcare system. Separate questionnaires were sent to chiefs of staff (n = 130) and GI service chiefs (n = 117), yielding response rates of 100% and 79%, respectively.

Respondents represented a wide distribution of geographic regions and institutional complexity levels, with 80% of GI groups based at high-complexity centers and 92% in urban locations. A minority (8%) reported the presence of a liver transplant program.

Data collection focused on the prevalence of POCUS use, types of clinical applications, institutional policies and training processes, and perceived or actual barriers to wider adoption. Barriers were sorted into three categories: training, equipment, and infrastructure.

Of the 93 GI service chiefs who participated in the survey, 44% reported that at least 1 gastroenterologist at their facility currently uses POCUS. Most common procedural uses were paracentesis (23%) and liver biopsy (13%), while ascites assessment (19%) and biliary visualization (7%) were the most common diagnostic uses.

Among the same respondents, 69% said they would support sending clinicians to a POCUS training course, and 37% said their teams had expressed an active interest in pursuing such training. Only 17% of facilities had a formal process in place to obtain POCUS training, and an equal proportion had implemented a facility-wide policy to guide its use.

Barriers to implementation were widespread and often multifactorial. 

Most challenges related to training: 48% of sites reported a lack of trained providers, 28% cited insufficient funding for training, 24% noted a lack of training opportunities, and 14% reported difficulty securing travel funds. 

Equipment limitations were also common, with 41% of sites lacking ultrasound machines and 27% lacking funding to purchase them. 

Institutional infrastructure posed further hurdles. Nearly a quarter of GI chiefs (23%) reported lacking a clinician champion to lead implementation, while others cited a lack of support staff, simulation space, privileging criteria, image archiving capabilities, or standardized reporting forms.

“Our findings on current POCUS use, training, barriers, and infrastructure can guide expansion of POCUS use and training among GI groups,” Dr. Thallapureddy and colleagues wrote, noting that early efforts to expand access to GI-specific POCUS training are already underway. 

They cited growing interest from national organizations such as the American Gastroenterological Association and the American Association for the Study of Liver Diseases, the latter of which piloted training workshops at the 2024 Liver Meeting. Similarly, the International Bowel Ultrasound Group now offers a 3-part certification program in intestinal ultrasound and is developing additional online and interactive modules to improve training accessibility.

The study was supported by the US Department of Veterans Affairs, Quality Enhancement Research Initiative Partnered Evaluation Initiative Grant, and the VA National Center for Patient Safety. The investigators reported no conflicts of interest.
 

Most GI service chiefs in the U.S. Veterans Affairs (VA) healthcare system support point-of-care ultrasound (POCUS) training, but fewer than half have the technology in their facility, according to a national survey.

Low POCUS uptake may be explained by substantial barriers to implementation, including lack of trained instructors, necessary equipment, and support staff, lead author Keerthi Thallapureddy, MD, of the University of Texas Health San Antonio, and colleagues, reported.

“POCUS is being increasingly used by gastroenterologists due to its portability and real-time diagnostic ability,” the investigators wrote in Gastro Hep Advances, but “there is limited understanding of how gastroenterologists use POCUS.”

To learn more, the investigators conducted a nationwide survey of the VA healthcare system. Separate questionnaires were sent to chiefs of staff (n = 130) and GI service chiefs (n = 117), yielding response rates of 100% and 79%, respectively.

Respondents represented a wide distribution of geographic regions and institutional complexity levels, with 80% of GI groups based at high-complexity centers and 92% in urban locations. A minority (8%) reported the presence of a liver transplant program.

Data collection focused on the prevalence of POCUS use, types of clinical applications, institutional policies and training processes, and perceived or actual barriers to wider adoption. Barriers were sorted into three categories: training, equipment, and infrastructure.

Of the 93 GI service chiefs who participated in the survey, 44% reported that at least 1 gastroenterologist at their facility currently uses POCUS. Most common procedural uses were paracentesis (23%) and liver biopsy (13%), while ascites assessment (19%) and biliary visualization (7%) were the most common diagnostic uses.

Among the same respondents, 69% said they would support sending clinicians to a POCUS training course, and 37% said their teams had expressed an active interest in pursuing such training. Only 17% of facilities had a formal process in place to obtain POCUS training, and an equal proportion had implemented a facility-wide policy to guide its use.

Barriers to implementation were widespread and often multifactorial. 

Most challenges related to training: 48% of sites reported a lack of trained providers, 28% cited insufficient funding for training, 24% noted a lack of training opportunities, and 14% reported difficulty securing travel funds. 

Equipment limitations were also common, with 41% of sites lacking ultrasound machines and 27% lacking funding to purchase them. 

Institutional infrastructure posed further hurdles. Nearly a quarter of GI chiefs (23%) reported lacking a clinician champion to lead implementation, while others cited a lack of support staff, simulation space, privileging criteria, image archiving capabilities, or standardized reporting forms.

“Our findings on current POCUS use, training, barriers, and infrastructure can guide expansion of POCUS use and training among GI groups,” Dr. Thallapureddy and colleagues wrote, noting that early efforts to expand access to GI-specific POCUS training are already underway. 

They cited growing interest from national organizations such as the American Gastroenterological Association and the American Association for the Study of Liver Diseases, the latter of which piloted training workshops at the 2024 Liver Meeting. Similarly, the International Bowel Ultrasound Group now offers a 3-part certification program in intestinal ultrasound and is developing additional online and interactive modules to improve training accessibility.

The study was supported by the US Department of Veterans Affairs, Quality Enhancement Research Initiative Partnered Evaluation Initiative Grant, and the VA National Center for Patient Safety. The investigators reported no conflicts of interest.
 

Most GI service chiefs in the U.S. Veterans Affairs (VA) healthcare system support point-of-care ultrasound (POCUS) training, but fewer than half have the technology in their facility, according to a national survey.

Low POCUS uptake may be explained by substantial barriers to implementation, including lack of trained instructors, necessary equipment, and support staff, lead author Keerthi Thallapureddy, MD, of the University of Texas Health San Antonio, and colleagues, reported.

“POCUS is being increasingly used by gastroenterologists due to its portability and real-time diagnostic ability,” the investigators wrote in Gastro Hep Advances, but “there is limited understanding of how gastroenterologists use POCUS.”

To learn more, the investigators conducted a nationwide survey of the VA healthcare system. Separate questionnaires were sent to chiefs of staff (n = 130) and GI service chiefs (n = 117), yielding response rates of 100% and 79%, respectively.

Respondents represented a wide distribution of geographic regions and institutional complexity levels, with 80% of GI groups based at high-complexity centers and 92% in urban locations. A minority (8%) reported the presence of a liver transplant program.

Data collection focused on the prevalence of POCUS use, types of clinical applications, institutional policies and training processes, and perceived or actual barriers to wider adoption. Barriers were sorted into three categories: training, equipment, and infrastructure.

Of the 93 GI service chiefs who participated in the survey, 44% reported that at least 1 gastroenterologist at their facility currently uses POCUS. Most common procedural uses were paracentesis (23%) and liver biopsy (13%), while ascites assessment (19%) and biliary visualization (7%) were the most common diagnostic uses.

Among the same respondents, 69% said they would support sending clinicians to a POCUS training course, and 37% said their teams had expressed an active interest in pursuing such training. Only 17% of facilities had a formal process in place to obtain POCUS training, and an equal proportion had implemented a facility-wide policy to guide its use.

Barriers to implementation were widespread and often multifactorial. 

Most challenges related to training: 48% of sites reported a lack of trained providers, 28% cited insufficient funding for training, 24% noted a lack of training opportunities, and 14% reported difficulty securing travel funds. 

Equipment limitations were also common, with 41% of sites lacking ultrasound machines and 27% lacking funding to purchase them. 

Institutional infrastructure posed further hurdles. Nearly a quarter of GI chiefs (23%) reported lacking a clinician champion to lead implementation, while others cited a lack of support staff, simulation space, privileging criteria, image archiving capabilities, or standardized reporting forms.

“Our findings on current POCUS use, training, barriers, and infrastructure can guide expansion of POCUS use and training among GI groups,” Dr. Thallapureddy and colleagues wrote, noting that early efforts to expand access to GI-specific POCUS training are already underway. 

They cited growing interest from national organizations such as the American Gastroenterological Association and the American Association for the Study of Liver Diseases, the latter of which piloted training workshops at the 2024 Liver Meeting. Similarly, the International Bowel Ultrasound Group now offers a 3-part certification program in intestinal ultrasound and is developing additional online and interactive modules to improve training accessibility.

The study was supported by the US Department of Veterans Affairs, Quality Enhancement Research Initiative Partnered Evaluation Initiative Grant, and the VA National Center for Patient Safety. The investigators reported no conflicts of interest.
 

Medications for inflammatory bowel disease (IBD) appear to have no impact on risk of incident malignancies among patients with a history of breast cancer, according to investigators.

These findings diminish concerns that IBD therapy could theoretically reactivate dormant micrometastases, lead author Guillaume Le Cosquer, MD, of Toulouse University Hospital, Toulouse, France, and colleagues, reported.

“In patients with IBD, medical management of subjects with a history of breast cancer is a frequent and unresolved problem for clinicians,” the investigators wrote in Clinical Gastroenterology and Hepatology (2024 Nov. doi: 10.1016/j.cgh.2024.09.034).

Previous studies have reported that conventional immunosuppressants and biologics do not increase risk of incident cancer among IBD patients with a prior nondigestive malignancy; however, recent guidelines from the European Crohn’s and Colitis Organisation (ECCO) suggest that data are insufficient to make associated recommendations, prompting the present study.

“[T]he major strength of our work is that it is the first to focus on the most frequent cancer (breast cancer) in patients with IBD only, with the longest follow-up after breast cancer in patients with IBD ever published,” Dr. Le Cosquer and colleagues noted.

The dataset included 207 patients with IBD and a history of breast cancer, drawn from 7 tertiary centers across France. 

The index date was the time of breast cancer diagnosis, and patients were followed for a median of 71 months. The median time from cancer diagnosis to initiation of IBD treatment was 28 months. 

First-line post-cancer treatments included conventional immunosuppressants (19.3%), anti–tumor necrosis factor (anti-TNF) agents (19.8%), vedolizumab (7.2%), and ustekinumab (1.9%). Approximately half (51.6%) received no immunosuppressive therapy during follow-up.

Over the study period, 42 incident cancers were recorded (20.3%), among which 34 were breast cancer recurrences. Adjusted incidence rates per 1000 person-years were 10.2 (95% CI, 6.0–16.4) in the untreated group and 28.9 (95% CI, 11.6–59.6) in patients exposed to immunosuppressive or biologic therapies (P = .0519). Incident cancer–free survival did not differ significantly between treated and untreated groups (P = .4796).

On multivariable analysis, independent predictors of incident cancer included T4d stage (P = .036), triple-negative status (P = .016), and follow-up duration shorter than 71 months (P = .005).

“[I]mmunosuppressant and biologic use in selected patients with IBD with prior breast cancer does not seem to increase the risk of incident cancer,” the investigators wrote, noting that the main predictors of cancer recurrence were known poor prognostic features of breast cancer.

Dr. Le Cosquer and colleagues acknowledged a lack of prospective safety data for biologic therapies among patients with prior malignancy, as these individuals are often excluded from clinical trials. Still, they underscored alignment between their findings and earlier retrospective studies, including analyses from the SAPPHIRE registry and Medicare data, which also found no significant increase in breast cancer recurrence with anti-TNF agents or newer biologics such as vedolizumab and ustekinumab. 

“Our findings will help clinicians to make decisions in multidisciplinary meetings to start immunosuppressants or biologics in case of IBD flare-up in these patients,” they concluded.

The investigators disclosed relationships with AbbVie, Janssen, Takeda, and others.

Medications for inflammatory bowel disease (IBD) appear to have no impact on risk of incident malignancies among patients with a history of breast cancer, according to investigators.

These findings diminish concerns that IBD therapy could theoretically reactivate dormant micrometastases, lead author Guillaume Le Cosquer, MD, of Toulouse University Hospital, Toulouse, France, and colleagues, reported.

“In patients with IBD, medical management of subjects with a history of breast cancer is a frequent and unresolved problem for clinicians,” the investigators wrote in Clinical Gastroenterology and Hepatology (2024 Nov. doi: 10.1016/j.cgh.2024.09.034).

Previous studies have reported that conventional immunosuppressants and biologics do not increase risk of incident cancer among IBD patients with a prior nondigestive malignancy; however, recent guidelines from the European Crohn’s and Colitis Organisation (ECCO) suggest that data are insufficient to make associated recommendations, prompting the present study.

“[T]he major strength of our work is that it is the first to focus on the most frequent cancer (breast cancer) in patients with IBD only, with the longest follow-up after breast cancer in patients with IBD ever published,” Dr. Le Cosquer and colleagues noted.

The dataset included 207 patients with IBD and a history of breast cancer, drawn from 7 tertiary centers across France. 

The index date was the time of breast cancer diagnosis, and patients were followed for a median of 71 months. The median time from cancer diagnosis to initiation of IBD treatment was 28 months. 

First-line post-cancer treatments included conventional immunosuppressants (19.3%), anti–tumor necrosis factor (anti-TNF) agents (19.8%), vedolizumab (7.2%), and ustekinumab (1.9%). Approximately half (51.6%) received no immunosuppressive therapy during follow-up.

Over the study period, 42 incident cancers were recorded (20.3%), among which 34 were breast cancer recurrences. Adjusted incidence rates per 1000 person-years were 10.2 (95% CI, 6.0–16.4) in the untreated group and 28.9 (95% CI, 11.6–59.6) in patients exposed to immunosuppressive or biologic therapies (P = .0519). Incident cancer–free survival did not differ significantly between treated and untreated groups (P = .4796).

On multivariable analysis, independent predictors of incident cancer included T4d stage (P = .036), triple-negative status (P = .016), and follow-up duration shorter than 71 months (P = .005).

“[I]mmunosuppressant and biologic use in selected patients with IBD with prior breast cancer does not seem to increase the risk of incident cancer,” the investigators wrote, noting that the main predictors of cancer recurrence were known poor prognostic features of breast cancer.

Dr. Le Cosquer and colleagues acknowledged a lack of prospective safety data for biologic therapies among patients with prior malignancy, as these individuals are often excluded from clinical trials. Still, they underscored alignment between their findings and earlier retrospective studies, including analyses from the SAPPHIRE registry and Medicare data, which also found no significant increase in breast cancer recurrence with anti-TNF agents or newer biologics such as vedolizumab and ustekinumab. 

“Our findings will help clinicians to make decisions in multidisciplinary meetings to start immunosuppressants or biologics in case of IBD flare-up in these patients,” they concluded.

The investigators disclosed relationships with AbbVie, Janssen, Takeda, and others.

Medications for inflammatory bowel disease (IBD) appear to have no impact on risk of incident malignancies among patients with a history of breast cancer, according to investigators.

These findings diminish concerns that IBD therapy could theoretically reactivate dormant micrometastases, lead author Guillaume Le Cosquer, MD, of Toulouse University Hospital, Toulouse, France, and colleagues, reported.

“In patients with IBD, medical management of subjects with a history of breast cancer is a frequent and unresolved problem for clinicians,” the investigators wrote in Clinical Gastroenterology and Hepatology (2024 Nov. doi: 10.1016/j.cgh.2024.09.034).

Previous studies have reported that conventional immunosuppressants and biologics do not increase risk of incident cancer among IBD patients with a prior nondigestive malignancy; however, recent guidelines from the European Crohn’s and Colitis Organisation (ECCO) suggest that data are insufficient to make associated recommendations, prompting the present study.

“[T]he major strength of our work is that it is the first to focus on the most frequent cancer (breast cancer) in patients with IBD only, with the longest follow-up after breast cancer in patients with IBD ever published,” Dr. Le Cosquer and colleagues noted.

The dataset included 207 patients with IBD and a history of breast cancer, drawn from 7 tertiary centers across France. 

The index date was the time of breast cancer diagnosis, and patients were followed for a median of 71 months. The median time from cancer diagnosis to initiation of IBD treatment was 28 months. 

First-line post-cancer treatments included conventional immunosuppressants (19.3%), anti–tumor necrosis factor (anti-TNF) agents (19.8%), vedolizumab (7.2%), and ustekinumab (1.9%). Approximately half (51.6%) received no immunosuppressive therapy during follow-up.

Over the study period, 42 incident cancers were recorded (20.3%), among which 34 were breast cancer recurrences. Adjusted incidence rates per 1000 person-years were 10.2 (95% CI, 6.0–16.4) in the untreated group and 28.9 (95% CI, 11.6–59.6) in patients exposed to immunosuppressive or biologic therapies (P = .0519). Incident cancer–free survival did not differ significantly between treated and untreated groups (P = .4796).

On multivariable analysis, independent predictors of incident cancer included T4d stage (P = .036), triple-negative status (P = .016), and follow-up duration shorter than 71 months (P = .005).

“[I]mmunosuppressant and biologic use in selected patients with IBD with prior breast cancer does not seem to increase the risk of incident cancer,” the investigators wrote, noting that the main predictors of cancer recurrence were known poor prognostic features of breast cancer.

Dr. Le Cosquer and colleagues acknowledged a lack of prospective safety data for biologic therapies among patients with prior malignancy, as these individuals are often excluded from clinical trials. Still, they underscored alignment between their findings and earlier retrospective studies, including analyses from the SAPPHIRE registry and Medicare data, which also found no significant increase in breast cancer recurrence with anti-TNF agents or newer biologics such as vedolizumab and ustekinumab. 

“Our findings will help clinicians to make decisions in multidisciplinary meetings to start immunosuppressants or biologics in case of IBD flare-up in these patients,” they concluded.

The investigators disclosed relationships with AbbVie, Janssen, Takeda, and others.

Like diners saving on drinks, endoscopists can safely forgo sterile water in favor of tap, reducing both environmental and financial costs, according to a recent narrative review.

“No direct evidence supports the recommendation and widespread use of sterile water during gastrointestinal endosco-py procedures,” lead author Deepak Agrawal, MD, chief of gastroenterology & hepatology at the Dell Medical School, University Texas at Austin, and colleagues, wrote in Gastro Hep Advances. “Guidelines recommending sterile water during endoscopy are based on limited evidence and mostly expert opinions.”

After reviewing the literature back to 1975, Dr. Agrawal and colleagues considered the use of sterile water in endoscopy via three frameworks: medical evidence and guidelines, environmental and broader health effects, and financial costs.

Only 2 studies – both from the 1990s – directly compared sterile and tap water use in endoscopy. Neither showed an increased risk of infection from tap water. In fact, some cultures from allegedly sterile water bottles grew pathogenic bacteria, while no patient complications were reported in either study.

“The recommendations for sterile water contradict observations in other medical care scenarios, for example, for the irrigation of open wounds,” Dr. Agrawal and colleagues noted. “Similarly, there is no benefit in using sterile water for enteral feeds in immunosuppressed patients, and tap water enemas are routinely acceptable for colon cleansing before sigmoidoscopies in all patients, irrespective of immune status.”

Current guidelines, including the 2021 US multisociety guideline on reprocessing flexible GI endoscopes and accessories, recommend sterile water for procedures involving mucosal penetration but acknowledge low-quality supporting evidence. These recommendations are based on outdated studies, some unrelated to GI endoscopy, Dr. Agrawal and colleagues pointed out, and rely heavily on cross-referenced opinion statements rather than clinical data.

They went on to suggest a concerning possibility: all those plastic bottles may actually cause more health problems than prevent them. The review estimates that the production and transportation of sterile water bottles contributes over 6,000 metric tons of emissions per year from US endoscopy units alone. What’s more, as discarded bottles break down, they release greenhouse gases and microplastics, the latter of which have been linked to cardiovascular disease, inflammatory bowel disease, and endocrine disruption.

Dr. Agrawal and colleagues also underscored the financial toxicity of sterile water bottles. Considering a 1-liter bottle of sterile water costs $3-10, an endoscopy unit performing 30 procedures per day spends approximately $1,000-3,000 per month on bottled water alone. Scaled nationally, the routine use of sterile water costs tens of millions of dollars each year, not counting indirect expenses associated with stocking and waste disposal.

Considering the dubious clinical upside against the apparent environmental and financial downsides, Dr. Agrawal and colleagues urged endoscopy units to rethink routine sterile water use. 

They proposed a pragmatic model: start the day with a new sterile or reusable bottle, refill with tap water for subsequent cases, and recycle the bottle at day’s end. Institutions should ensure their tap water meets safety standards, they added, such as those outlined in the Joint Commission’s 2022 R3 Report on standards for water management.

Dr. Agrawal and colleagues also called on GI societies to revise existing guidance to reflect today’s clinical and environmental realities. Until strong evidence supports the need for sterile water, they wrote, the smarter, safer, and more sustainable option may be simply turning on the tap.

The investigators disclosed relationships with Guardant, Exact Sciences, Freenome, and others.
 

Like diners saving on drinks, endoscopists can safely forgo sterile water in favor of tap, reducing both environmental and financial costs, according to a recent narrative review.

“No direct evidence supports the recommendation and widespread use of sterile water during gastrointestinal endosco-py procedures,” lead author Deepak Agrawal, MD, chief of gastroenterology & hepatology at the Dell Medical School, University Texas at Austin, and colleagues, wrote in Gastro Hep Advances. “Guidelines recommending sterile water during endoscopy are based on limited evidence and mostly expert opinions.”

After reviewing the literature back to 1975, Dr. Agrawal and colleagues considered the use of sterile water in endoscopy via three frameworks: medical evidence and guidelines, environmental and broader health effects, and financial costs.

Only 2 studies – both from the 1990s – directly compared sterile and tap water use in endoscopy. Neither showed an increased risk of infection from tap water. In fact, some cultures from allegedly sterile water bottles grew pathogenic bacteria, while no patient complications were reported in either study.

“The recommendations for sterile water contradict observations in other medical care scenarios, for example, for the irrigation of open wounds,” Dr. Agrawal and colleagues noted. “Similarly, there is no benefit in using sterile water for enteral feeds in immunosuppressed patients, and tap water enemas are routinely acceptable for colon cleansing before sigmoidoscopies in all patients, irrespective of immune status.”

Current guidelines, including the 2021 US multisociety guideline on reprocessing flexible GI endoscopes and accessories, recommend sterile water for procedures involving mucosal penetration but acknowledge low-quality supporting evidence. These recommendations are based on outdated studies, some unrelated to GI endoscopy, Dr. Agrawal and colleagues pointed out, and rely heavily on cross-referenced opinion statements rather than clinical data.

They went on to suggest a concerning possibility: all those plastic bottles may actually cause more health problems than prevent them. The review estimates that the production and transportation of sterile water bottles contributes over 6,000 metric tons of emissions per year from US endoscopy units alone. What’s more, as discarded bottles break down, they release greenhouse gases and microplastics, the latter of which have been linked to cardiovascular disease, inflammatory bowel disease, and endocrine disruption.

Dr. Agrawal and colleagues also underscored the financial toxicity of sterile water bottles. Considering a 1-liter bottle of sterile water costs $3-10, an endoscopy unit performing 30 procedures per day spends approximately $1,000-3,000 per month on bottled water alone. Scaled nationally, the routine use of sterile water costs tens of millions of dollars each year, not counting indirect expenses associated with stocking and waste disposal.

Considering the dubious clinical upside against the apparent environmental and financial downsides, Dr. Agrawal and colleagues urged endoscopy units to rethink routine sterile water use. 

They proposed a pragmatic model: start the day with a new sterile or reusable bottle, refill with tap water for subsequent cases, and recycle the bottle at day’s end. Institutions should ensure their tap water meets safety standards, they added, such as those outlined in the Joint Commission’s 2022 R3 Report on standards for water management.

Dr. Agrawal and colleagues also called on GI societies to revise existing guidance to reflect today’s clinical and environmental realities. Until strong evidence supports the need for sterile water, they wrote, the smarter, safer, and more sustainable option may be simply turning on the tap.

The investigators disclosed relationships with Guardant, Exact Sciences, Freenome, and others.
 

Like diners saving on drinks, endoscopists can safely forgo sterile water in favor of tap, reducing both environmental and financial costs, according to a recent narrative review.

“No direct evidence supports the recommendation and widespread use of sterile water during gastrointestinal endosco-py procedures,” lead author Deepak Agrawal, MD, chief of gastroenterology & hepatology at the Dell Medical School, University Texas at Austin, and colleagues, wrote in Gastro Hep Advances. “Guidelines recommending sterile water during endoscopy are based on limited evidence and mostly expert opinions.”

After reviewing the literature back to 1975, Dr. Agrawal and colleagues considered the use of sterile water in endoscopy via three frameworks: medical evidence and guidelines, environmental and broader health effects, and financial costs.

Only 2 studies – both from the 1990s – directly compared sterile and tap water use in endoscopy. Neither showed an increased risk of infection from tap water. In fact, some cultures from allegedly sterile water bottles grew pathogenic bacteria, while no patient complications were reported in either study.

“The recommendations for sterile water contradict observations in other medical care scenarios, for example, for the irrigation of open wounds,” Dr. Agrawal and colleagues noted. “Similarly, there is no benefit in using sterile water for enteral feeds in immunosuppressed patients, and tap water enemas are routinely acceptable for colon cleansing before sigmoidoscopies in all patients, irrespective of immune status.”

Current guidelines, including the 2021 US multisociety guideline on reprocessing flexible GI endoscopes and accessories, recommend sterile water for procedures involving mucosal penetration but acknowledge low-quality supporting evidence. These recommendations are based on outdated studies, some unrelated to GI endoscopy, Dr. Agrawal and colleagues pointed out, and rely heavily on cross-referenced opinion statements rather than clinical data.

They went on to suggest a concerning possibility: all those plastic bottles may actually cause more health problems than prevent them. The review estimates that the production and transportation of sterile water bottles contributes over 6,000 metric tons of emissions per year from US endoscopy units alone. What’s more, as discarded bottles break down, they release greenhouse gases and microplastics, the latter of which have been linked to cardiovascular disease, inflammatory bowel disease, and endocrine disruption.

Dr. Agrawal and colleagues also underscored the financial toxicity of sterile water bottles. Considering a 1-liter bottle of sterile water costs $3-10, an endoscopy unit performing 30 procedures per day spends approximately $1,000-3,000 per month on bottled water alone. Scaled nationally, the routine use of sterile water costs tens of millions of dollars each year, not counting indirect expenses associated with stocking and waste disposal.

Considering the dubious clinical upside against the apparent environmental and financial downsides, Dr. Agrawal and colleagues urged endoscopy units to rethink routine sterile water use. 

They proposed a pragmatic model: start the day with a new sterile or reusable bottle, refill with tap water for subsequent cases, and recycle the bottle at day’s end. Institutions should ensure their tap water meets safety standards, they added, such as those outlined in the Joint Commission’s 2022 R3 Report on standards for water management.

Dr. Agrawal and colleagues also called on GI societies to revise existing guidance to reflect today’s clinical and environmental realities. Until strong evidence supports the need for sterile water, they wrote, the smarter, safer, and more sustainable option may be simply turning on the tap.

The investigators disclosed relationships with Guardant, Exact Sciences, Freenome, and others.
 

Among hospitalized patients with cirrhosis, a machine learning (ML) model enhanced mortality prediction compared with traditional methods and was consistent across country income levels in a large global study.

“This highly inclusive, representative, and globally derived model has been externally validated,” Jasmohan Bajaj, MD, AGAF, professor of medicine at Virginia Commonwealth University in Richmond, Virginia, told GI & Hepatology News. “This gives us a crystal ball. It helps hospital teams, transplant centers, gastroenterology and intensive care unit services triage and prioritize patients more effectively.”

The study supporting the model, which Bajaj said “could be used at this stage,” was published online in Gastroenterology. The model is available for downloading at https://silveys.shinyapps.io/app_cleared/.

 

CLEARED Cohort Analyzed

Wide variations across the world regarding available resources, outpatient services, reasons for admission, and etiologies of cirrhosis can influence patient outcomes, according to Bajaj and colleagues. Therefore, they sought to use ML approaches to improve prognostication for all countries.

They analyzed admission-day data from the prospective Chronic Liver Disease Evolution And Registry for Events and Decompensation (CLEARED) consortium, which includes inpatients with cirrhosis enrolled from six continents. The analysis compared ML approaches with logistical regression to predict inpatient mortality.

The researchers performed internal validation (75/25 split) and subdivision using World-Bank income status: low/low-middle (L-LMIC), upper middle (UMIC), and high (HIC). They determined that the ML model with the best area-under-the-curve (AUC) would be externally validated in a US-Veteran cirrhosis inpatient population.

The CLEARED cohort included 7239 cirrhosis inpatients (mean age, 56 years; 64% men; median MELD-Na, 25) from 115 centers globally; 22.5% of centers belonged to LMICs, 41% to UMICs, and 34% to HICs.

A total of 808 patients (11.1%) died in the hospital.

Random-Forest analysis showed the best AUC (0.815) with high calibration. This was significantly better than parametric logistic regression (AUC, 0.774) and LASSO (AUC, 0.787) models.

Random-Forest also was better than logistic regression regardless of country income-level: HIC (AUC,0.806), UMIC (AUC, 0.867), and L-LMICs (AUC, 0.768).

Of the top 15 important variables selected from Random-Forest, admission for acute kidney injury, hepatic encephalopathy, high MELD-Na/white blood count, and not being in high income country were variables most predictive of mortality.

In contrast, higher albumin, hemoglobin, diuretic use on admission, viral etiology, and being in a high-income country were most protective.

The Random-Forest model was validated in 28,670 veterans (mean age, 67 years; 96% men; median MELD-Na,15), with an inpatient mortality of 4% (1158 patients).

The final Random-Forest model, using 48 of the 67 original covariates, attained a strong AUC of 0.859. A refit version using only the top 15 variables achieved a comparable AUC of 0.851.

 

Clinical Relevance

“Cirrhosis and resultant organ failures remain a dynamic and multidisciplinary problem,” Bajaj noted. “Machine learning techniques are one part of multi-faceted management strategy that is required in this population.”

If patients fall into the high-risk category, he said, “careful consultation with patients, families, and clinical teams is needed before providing information, including where this model was derived from. The results of these discussions could be instructive regarding decisions for transfer, more aggressive monitoring/ICU transfer, palliative care or transplant assessments.”

Meena B. Bansal, MD, system chief, Division of Liver Diseases, Mount Sinai Health System in New York City, called the tool “very promising.” However, she told GI & Hepatology News, “it was validated on a VA [Veterans Affairs] cohort, which is a bit different than the cohort of patients seen at Mount Sinai. Therefore, validation in more academic tertiary care medical centers with high volume liver transplant would be helpful.”

 

Furthermore, said Bansal, who was not involved in the study, “they excluded those that receiving a liver transplant, and while only a small number, this is an important limitation.”

Nevertheless, she added, “Artificial intelligence has great potential in predictive risk models and will likely be a tool that assists for risk stratification, clinical management, and hopefully improved clinical outcomes.”

This study was partly supported by a VA Merit review to Bajaj and the National Center for Advancing Translational Sciences, National Institutes of Health. No conflicts of interest were reported by any author.

A version of this article appeared on Medscape.com.

Among hospitalized patients with cirrhosis, a machine learning (ML) model enhanced mortality prediction compared with traditional methods and was consistent across country income levels in a large global study.

“This highly inclusive, representative, and globally derived model has been externally validated,” Jasmohan Bajaj, MD, AGAF, professor of medicine at Virginia Commonwealth University in Richmond, Virginia, told GI & Hepatology News. “This gives us a crystal ball. It helps hospital teams, transplant centers, gastroenterology and intensive care unit services triage and prioritize patients more effectively.”

The study supporting the model, which Bajaj said “could be used at this stage,” was published online in Gastroenterology. The model is available for downloading at https://silveys.shinyapps.io/app_cleared/.

 

CLEARED Cohort Analyzed

Wide variations across the world regarding available resources, outpatient services, reasons for admission, and etiologies of cirrhosis can influence patient outcomes, according to Bajaj and colleagues. Therefore, they sought to use ML approaches to improve prognostication for all countries.

They analyzed admission-day data from the prospective Chronic Liver Disease Evolution And Registry for Events and Decompensation (CLEARED) consortium, which includes inpatients with cirrhosis enrolled from six continents. The analysis compared ML approaches with logistical regression to predict inpatient mortality.

The researchers performed internal validation (75/25 split) and subdivision using World-Bank income status: low/low-middle (L-LMIC), upper middle (UMIC), and high (HIC). They determined that the ML model with the best area-under-the-curve (AUC) would be externally validated in a US-Veteran cirrhosis inpatient population.

The CLEARED cohort included 7239 cirrhosis inpatients (mean age, 56 years; 64% men; median MELD-Na, 25) from 115 centers globally; 22.5% of centers belonged to LMICs, 41% to UMICs, and 34% to HICs.

A total of 808 patients (11.1%) died in the hospital.

Random-Forest analysis showed the best AUC (0.815) with high calibration. This was significantly better than parametric logistic regression (AUC, 0.774) and LASSO (AUC, 0.787) models.

Random-Forest also was better than logistic regression regardless of country income-level: HIC (AUC,0.806), UMIC (AUC, 0.867), and L-LMICs (AUC, 0.768).

Of the top 15 important variables selected from Random-Forest, admission for acute kidney injury, hepatic encephalopathy, high MELD-Na/white blood count, and not being in high income country were variables most predictive of mortality.

In contrast, higher albumin, hemoglobin, diuretic use on admission, viral etiology, and being in a high-income country were most protective.

The Random-Forest model was validated in 28,670 veterans (mean age, 67 years; 96% men; median MELD-Na,15), with an inpatient mortality of 4% (1158 patients).

The final Random-Forest model, using 48 of the 67 original covariates, attained a strong AUC of 0.859. A refit version using only the top 15 variables achieved a comparable AUC of 0.851.

 

Clinical Relevance

“Cirrhosis and resultant organ failures remain a dynamic and multidisciplinary problem,” Bajaj noted. “Machine learning techniques are one part of multi-faceted management strategy that is required in this population.”

If patients fall into the high-risk category, he said, “careful consultation with patients, families, and clinical teams is needed before providing information, including where this model was derived from. The results of these discussions could be instructive regarding decisions for transfer, more aggressive monitoring/ICU transfer, palliative care or transplant assessments.”

Meena B. Bansal, MD, system chief, Division of Liver Diseases, Mount Sinai Health System in New York City, called the tool “very promising.” However, she told GI & Hepatology News, “it was validated on a VA [Veterans Affairs] cohort, which is a bit different than the cohort of patients seen at Mount Sinai. Therefore, validation in more academic tertiary care medical centers with high volume liver transplant would be helpful.”

 

Furthermore, said Bansal, who was not involved in the study, “they excluded those that receiving a liver transplant, and while only a small number, this is an important limitation.”

Nevertheless, she added, “Artificial intelligence has great potential in predictive risk models and will likely be a tool that assists for risk stratification, clinical management, and hopefully improved clinical outcomes.”

This study was partly supported by a VA Merit review to Bajaj and the National Center for Advancing Translational Sciences, National Institutes of Health. No conflicts of interest were reported by any author.

A version of this article appeared on Medscape.com.

Among hospitalized patients with cirrhosis, a machine learning (ML) model enhanced mortality prediction compared with traditional methods and was consistent across country income levels in a large global study.

“This highly inclusive, representative, and globally derived model has been externally validated,” Jasmohan Bajaj, MD, AGAF, professor of medicine at Virginia Commonwealth University in Richmond, Virginia, told GI & Hepatology News. “This gives us a crystal ball. It helps hospital teams, transplant centers, gastroenterology and intensive care unit services triage and prioritize patients more effectively.”

The study supporting the model, which Bajaj said “could be used at this stage,” was published online in Gastroenterology. The model is available for downloading at https://silveys.shinyapps.io/app_cleared/.

 

CLEARED Cohort Analyzed

Wide variations across the world regarding available resources, outpatient services, reasons for admission, and etiologies of cirrhosis can influence patient outcomes, according to Bajaj and colleagues. Therefore, they sought to use ML approaches to improve prognostication for all countries.

They analyzed admission-day data from the prospective Chronic Liver Disease Evolution And Registry for Events and Decompensation (CLEARED) consortium, which includes inpatients with cirrhosis enrolled from six continents. The analysis compared ML approaches with logistical regression to predict inpatient mortality.

The researchers performed internal validation (75/25 split) and subdivision using World-Bank income status: low/low-middle (L-LMIC), upper middle (UMIC), and high (HIC). They determined that the ML model with the best area-under-the-curve (AUC) would be externally validated in a US-Veteran cirrhosis inpatient population.

The CLEARED cohort included 7239 cirrhosis inpatients (mean age, 56 years; 64% men; median MELD-Na, 25) from 115 centers globally; 22.5% of centers belonged to LMICs, 41% to UMICs, and 34% to HICs.

A total of 808 patients (11.1%) died in the hospital.

Random-Forest analysis showed the best AUC (0.815) with high calibration. This was significantly better than parametric logistic regression (AUC, 0.774) and LASSO (AUC, 0.787) models.

Random-Forest also was better than logistic regression regardless of country income-level: HIC (AUC,0.806), UMIC (AUC, 0.867), and L-LMICs (AUC, 0.768).

Of the top 15 important variables selected from Random-Forest, admission for acute kidney injury, hepatic encephalopathy, high MELD-Na/white blood count, and not being in high income country were variables most predictive of mortality.

In contrast, higher albumin, hemoglobin, diuretic use on admission, viral etiology, and being in a high-income country were most protective.

The Random-Forest model was validated in 28,670 veterans (mean age, 67 years; 96% men; median MELD-Na,15), with an inpatient mortality of 4% (1158 patients).

The final Random-Forest model, using 48 of the 67 original covariates, attained a strong AUC of 0.859. A refit version using only the top 15 variables achieved a comparable AUC of 0.851.

 

Clinical Relevance

“Cirrhosis and resultant organ failures remain a dynamic and multidisciplinary problem,” Bajaj noted. “Machine learning techniques are one part of multi-faceted management strategy that is required in this population.”

If patients fall into the high-risk category, he said, “careful consultation with patients, families, and clinical teams is needed before providing information, including where this model was derived from. The results of these discussions could be instructive regarding decisions for transfer, more aggressive monitoring/ICU transfer, palliative care or transplant assessments.”

Meena B. Bansal, MD, system chief, Division of Liver Diseases, Mount Sinai Health System in New York City, called the tool “very promising.” However, she told GI & Hepatology News, “it was validated on a VA [Veterans Affairs] cohort, which is a bit different than the cohort of patients seen at Mount Sinai. Therefore, validation in more academic tertiary care medical centers with high volume liver transplant would be helpful.”

 

Furthermore, said Bansal, who was not involved in the study, “they excluded those that receiving a liver transplant, and while only a small number, this is an important limitation.”

Nevertheless, she added, “Artificial intelligence has great potential in predictive risk models and will likely be a tool that assists for risk stratification, clinical management, and hopefully improved clinical outcomes.”

This study was partly supported by a VA Merit review to Bajaj and the National Center for Advancing Translational Sciences, National Institutes of Health. No conflicts of interest were reported by any author.

A version of this article appeared on Medscape.com.