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Lower Gastrointestinal Bleeding: Two Perspectives
Dear colleagues,
: What is the role and optimal timing of colonoscopy? How can we best utilize radiologic studies like CTA or tagged RBC scans? How should we manage patients with recurrent or intermittent bleeding that defies localization?
In this issue of Perspectives, Dr. David Wan, Dr. Fredella Lee, and Dr. Zeyad Metwalli offer their expert insights on these difficult questions. Dr. Wan, drawing on over 15 years of experience as a GI hospitalist, shares – along with his coauthor Dr. Lee – a pragmatic approach to LGIB based on clinical patterns, evolving data, and multidisciplinary collaboration. Dr. Metwalli provides the interventional radiologist’s perspective, highlighting how angiographic techniques can complement GI management and introducing novel IR strategies for patients with recurrent or elusive bleeding.
We hope their perspectives will offer valuable guidance for your practice. Join the conversation on X at @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.
Management of Lower Gastrointestinal Bleeds: GI Perspective
BY FREDELLA LEE, MD; DAVID WAN, MD
Acute lower gastrointestinal bleeding (LGIB) presents unique challenges. Much of this stems from the natural history of diverticular bleeding, the most common etiology of LGIB.
First, while bleeding can be severe, most will spontaneously stop. Second, despite our best efforts with imaging or colonoscopy, finding an intervenable lesion is rare. Third, LGIB has significant rates of rebleeding that are unpredictable.
While serving as a GI hospitalist for 15 years and after managing over 300 cases of LGIB, I often find myself frustrated and colonoscopy feels futile. So how can we rationally approach these patients? We will focus on three clinical questions to develop a framework for LGIB management.
- What is the role and timing for a colonoscopy?
- How do we best utilize radiologic tests?
- How can we prevent recurrent LGIB?
The Role of Colonoscopy
Traditionally, colonoscopy within 24 hours of presentation was recommended. This was based on retrospective cohort data showing higher endoscopic intervention rates and better clinical outcomes. However, this protocol requires patients to drink a significant volume of bowel preparation over a few hours (often requiring an NGT) to achieve clear rectal effluent. Moreover, one needs to mobilize a team (i.e., nurse, technician, anesthesiologist, and gastroenterologist), and find an appropriate location to scope (i.e., ED, ICU, or OR), Understandably, this is challenging, especially overnight. When the therapeutic yield is relatively low, this approach quickly loses enthusiasm.
Importantly, meta-analyses of the randomized controlled trials, have shown that urgent colonoscopies (<24 hours upon presentation), compared to elective colonoscopies (>24 hours upon presentation), do not improve clinical outcomes such as re-bleeding rates, transfusion requirements, mortality, or length of stay. In these studies, the endoscopic intervention rates were 17-34%, however, observational data shows rates of only 8%. In our practice, we will use a clear cap attachment device and water jet irrigation to increase the odds of detecting an active source of bleeding. Colonoscopy has a diagnostic yield of 95% – despite its low therapeutic yield; and while diverticular bleeds constitute up to 64% of cases, one does not want to miss colorectal cancer or other diagnoses. Regardless, there is generally no urgency to perform a colonoscopy. To quote a colleague, Dr. Elizabeth Ross, “there is no such thing as door-to-butt time.”
The Role of Radiology
Given the limits of colonoscopy, can radiographic tests such as computed tomography angiography (CTA) or tagged red blood cell (RBC) scan be helpful? Multiple studies have suggested using CTA as the initial diagnostic test. The advantages of CTAs are:
- Fast, readily available, and does not require a bowel preparation
- If negative, CTAs portend a good prognosis and make it highly unlikely to detect active extravasation on visceral angiography
- If positive, can localize the source of bleed and increase the success of intervention
Whether a positive CTA should be followed with a colonoscopy or visceral angiography remains unclear. Studies show that positive CTAs increase the detection rate of stigmata of recent hemorrhage on colonoscopy. Positive CTAs can also identify a target for embolization by interventional radiology (IR). Though an important caveat is that the success rate of embolization is highest when performed within 90 minutes of a positive CTA. This highlights that if you have IR availability, it is critical to have clear communication, a well-defined protocol, and collaboration among disciplines (i.e., ED, medical team, GI, and IR).
At our institution, we have implemented a CTA-guided protocol for severe LGIB. Those with positive CTAs are referred immediately to IR for embolization. If the embolization is unsuccessful or CTA is negative, the patient will be planned for a non-urgent inpatient colonoscopy. However, our unpublished data and other studies have shown that the overall CTA positivity rates are only between 16-22%. Moreover, one randomized controlled trial comparing CTA versus colonoscopy as an initial test did not show any meaningful difference in clinical outcomes. Thus, the benefit of CTA and the best approach to positive CTAs remains in question.
Lastly, people often ask about the utility of RBC nuclear scans. While they can detect bleeds at a slower rate (as low as 0.1 mL/min) compared to CTA (at least 0.4 mL/min), there are many limitations. RBC scans take time, are not available 24-7, and cannot precisely localize the site of bleeding. Therefore, we rarely recommend them for LGIB.
Approach to Recurrent Diverticular Bleeding
Unfortunately, diverticular bleeding recurs in the hospital 14% of the time and up to 25% at 5 years. When this occurs, is it worthwhile to repeat another colonoscopy or CTA?
Given the lack of clear data, we have adopted a shared decision-making framework with patients. Oftentimes, these patients are older and have significant co-morbidities, and undergoing bowel preparation, anesthesia, and colonoscopy is not trivial. If the patient is stable and prior work-up has excluded pertinent alternative diagnoses other than diverticular bleeding, then we tell patients the chance of finding an intervenable lesion is low and opt for conservative management. Meanwhile, if the patient has persistent, hemodynamically significant bleeding, we recommend a CTA based on the rationale discussed previously.
The most important clinical decision may not be about scoping or obtaining a CTA – it is medication management. If they are taking NSAIDs, they should be discontinued. If antiplatelet or anticoagulation agents were held, they should be restarted promptly in individuals with significant thrombotic risk given studies showing that while rebleeding rates may increase, overall mortality decreases.
In summary, managing LGIB and altering its natural history with either endoscopic or radiographic means is challenging. More studies are needed to guide the optimal approach. Reassuringly, most bleeding self-resolves and patients have good clinical outcomes.
Dr. Lee is a resident physician at New York Presbyterian Weill Cornell Medical Center, New York, NY. Dr. Wan is associate professor of clinical medicine at Weill Cornell Medicine, New York, N.Y. They declare no conflicts of interest.
Lower Gastrointestinal Bleeding: An Interventional Radiologist’s Perspective
BY ZEYAD METWALLI, MD, FSIR
When colonoscopy fails to localize and/or stop lower gastrointestinal bleeding (LGIB), catheter angiography has been commonly employed as a tool for both diagnosis and treatment of bleeding with embolization. Nuclear medicine or CT imaging studies can serve as useful adjuncts for confirming active bleeding and localizing the site of bleeding prior to angiography, particularly if this information is not provided by colonoscopy. Provocative mesenteric angiography has also become increasingly popular as a troubleshooting technique in patients with initially negative angiography.
Localization of Lower Gastrointestinal Bleeding
Radionuclide technetium-99m-lableled red blood cell scintigraphy (RBCS), also known as tagged RBC scintigraphy, has been in use since the early 1980s for investigation of acute gastrointestinal bleeding. RBCS has a high sensitivity for detection of active bleeding with a theoretical ability to detect bleeding at rates as low as 0.04-0.2 mL/minute.
Imaging protocols vary but should include dynamic images, which may aid in localization of bleeding. The relatively long half-life of the tracer used for imaging allows for delayed imaging 12 to 24 hours after injection. This can be useful to confirm active bleeding, particularly when bleeding is intermittent and is not visible on initial images.
With the advent of computed tomography angiography (CTA), which continues to increase in speed, imaging quality and availability, the use of RBCS for evaluation of LGIB has declined. CTA is quicker to perform than RBCS and allows for detection of bleeding as well as accurate anatomic localization, which can guide interventions.
CTA provides a more comprehensive anatomic evaluation, which can aid in the diagnosis of a wide variety of intra-abdominal issues. Conversely, CTA may be less sensitive than RBCS for detection of slower acute bleeding, detecting bleeding at rates of 0.1-1 mL/min. In addition, intermittent bleeding which has temporarily stopped at the time of CTA may evade detection.
Lastly, CTA may not be appropriate in patients with impaired renal function due to risk of contrast-induced nephropathy, particularly in patients with acute kidney injury, which commonly afflicts hospitalized patients with LGIB. Prophylaxis with normal saline hydration should be employed aggressively in patients with impaired renal function, particularly when eGFR is less than 30 mL/minute. Iodinated contrast should be used judiciously in these patients.
In clinical practice, CTA and RBCS have a similar ability to confirm the presence or absence of clinically significant active gastrointestinal bleeding. Given the greater ability to rapidly localize the bleeding site with CTA, this is generally preferred over RBCS unless there is a contraindication to performing CTA, such as severe contrast allergy or high risk for development of contrast-induced nephropathy.
Role of Catheter Angiography and Embolization
Mesenteric angiography is a well-established technique for both detection and treatment of LGIB. Hemodynamic instability and need for packed RBC transfusion increases the likelihood of positive angiography. Limitations include reduced sensitivity for detection of bleeding slower than 0.5-1 mL/minute as well as the intermittent nature of LGIB, which will often resolve spontaneously. Angiography is variably successful in the literature with a diagnostic yield between 40-80%, which encompasses the rate of success in my own practice.
Once bleeding is identified, microcatheter placement within the feeding vessel as close as possible to the site of bleeding is important to ensure treatment efficacy and to limit risk of complications such as non-target embolization and bowel ischemia. Once the feeding vessel is selected with a microcatheter, embolization can be accomplished with a wide variety of tools including metallic coils, liquid embolic agents, and particles. In the treatment of LGIB, liquid embolic agents (e.g., n-butyl cyanoacrylate or NBCA, ethylene vinyl alcohol copolymer, etc.) and particles should be used judiciously as distal penetration increases the risk of bowel ischemia and procedure-related morbidity. For this reason, metallic coils are often preferred in the treatment of LGIB.
Although the source of bleeding is variable and may include diverticulosis, recent polypectomy, ulcer, tumor or angiodysplasia, the techniques employed are similar. Accurate and distal microcatheter selection is a key driver for successful embolization and minimizing the risk of bowel ischemia. Small intestinal bleeds can be challenging to treat due to the redundant supply of the arterial arcades supplying small bowel and may require occlusion of several branches to achieve hemostasis. This approach must be balanced with the risk of developing ischemia after embolization. Angiodysplasia, a less frequently encountered culprit of LGIB, may also be managed with selective embolization with many reports of successful treatment with liquid embolic agents such as NBCA mixed with ethiodized oil.
Provocative Mesenteric Angiography for Occult Bleeding
When initial angiography in a patient with suspected active LGIB is negative, provocative angiography can be considered to uncover an intermittent bleed. This may be particularly helpful in a patient where active bleeding is confirmed on a prior diagnostic test.
The approach to provocative mesenteric angiography varies by center, and a variety of agents have been used to provoke bleeding including heparin, vasodilators (i.e., nitroglycerin, verapamil, etc.) and thrombolytics (i.e., tPA), often in combination. Thrombolytics can be administered directly into the territory of interest (i.e., superior mesenteric or inferior mesenteric artery) while heparin may be administered systemically or directly into the catheterized artery. Reported success rates for provoking angiographically visible bleeding vary, but most larger series report a 40-50% success rate. The newly detected bleeding can then be treated with either embolization or surgery. A surgeon should be involved and available when provocative angiography is planned should bleeding fail to be controlled by embolization.
In summary, when colonoscopy fails to identify or control lower gastrointestinal bleeding (LGIB), imaging techniques such as RBCS and CTA play a crucial role in localizing active bleeding. While RBCS is highly sensitive, especially for intermittent or slow bleeding, CTA offers faster, more detailed anatomical information and is typically preferred unless contraindicated by renal issues or contrast allergies. Catheter-based mesenteric angiography is a well-established method for both diagnosing and treating LGIB, often using metallic coils to minimize complications like bowel ischemia. In cases where initial angiography is negative, provocative angiography – using agents like heparin or thrombolytics – may help unmask intermittent bleeding, allowing for targeted embolization or surgical intervention.
Dr. Metwalli is associate professor in the Department of Interventional Radiology, Division of Diagnostic Imaging, at The University of Texas MD Anderson Cancer Center, Houston, Texas. He declares no conflicts of interest.
Dear colleagues,
: What is the role and optimal timing of colonoscopy? How can we best utilize radiologic studies like CTA or tagged RBC scans? How should we manage patients with recurrent or intermittent bleeding that defies localization?
In this issue of Perspectives, Dr. David Wan, Dr. Fredella Lee, and Dr. Zeyad Metwalli offer their expert insights on these difficult questions. Dr. Wan, drawing on over 15 years of experience as a GI hospitalist, shares – along with his coauthor Dr. Lee – a pragmatic approach to LGIB based on clinical patterns, evolving data, and multidisciplinary collaboration. Dr. Metwalli provides the interventional radiologist’s perspective, highlighting how angiographic techniques can complement GI management and introducing novel IR strategies for patients with recurrent or elusive bleeding.
We hope their perspectives will offer valuable guidance for your practice. Join the conversation on X at @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.
Management of Lower Gastrointestinal Bleeds: GI Perspective
BY FREDELLA LEE, MD; DAVID WAN, MD
Acute lower gastrointestinal bleeding (LGIB) presents unique challenges. Much of this stems from the natural history of diverticular bleeding, the most common etiology of LGIB.
First, while bleeding can be severe, most will spontaneously stop. Second, despite our best efforts with imaging or colonoscopy, finding an intervenable lesion is rare. Third, LGIB has significant rates of rebleeding that are unpredictable.
While serving as a GI hospitalist for 15 years and after managing over 300 cases of LGIB, I often find myself frustrated and colonoscopy feels futile. So how can we rationally approach these patients? We will focus on three clinical questions to develop a framework for LGIB management.
- What is the role and timing for a colonoscopy?
- How do we best utilize radiologic tests?
- How can we prevent recurrent LGIB?
The Role of Colonoscopy
Traditionally, colonoscopy within 24 hours of presentation was recommended. This was based on retrospective cohort data showing higher endoscopic intervention rates and better clinical outcomes. However, this protocol requires patients to drink a significant volume of bowel preparation over a few hours (often requiring an NGT) to achieve clear rectal effluent. Moreover, one needs to mobilize a team (i.e., nurse, technician, anesthesiologist, and gastroenterologist), and find an appropriate location to scope (i.e., ED, ICU, or OR), Understandably, this is challenging, especially overnight. When the therapeutic yield is relatively low, this approach quickly loses enthusiasm.
Importantly, meta-analyses of the randomized controlled trials, have shown that urgent colonoscopies (<24 hours upon presentation), compared to elective colonoscopies (>24 hours upon presentation), do not improve clinical outcomes such as re-bleeding rates, transfusion requirements, mortality, or length of stay. In these studies, the endoscopic intervention rates were 17-34%, however, observational data shows rates of only 8%. In our practice, we will use a clear cap attachment device and water jet irrigation to increase the odds of detecting an active source of bleeding. Colonoscopy has a diagnostic yield of 95% – despite its low therapeutic yield; and while diverticular bleeds constitute up to 64% of cases, one does not want to miss colorectal cancer or other diagnoses. Regardless, there is generally no urgency to perform a colonoscopy. To quote a colleague, Dr. Elizabeth Ross, “there is no such thing as door-to-butt time.”
The Role of Radiology
Given the limits of colonoscopy, can radiographic tests such as computed tomography angiography (CTA) or tagged red blood cell (RBC) scan be helpful? Multiple studies have suggested using CTA as the initial diagnostic test. The advantages of CTAs are:
- Fast, readily available, and does not require a bowel preparation
- If negative, CTAs portend a good prognosis and make it highly unlikely to detect active extravasation on visceral angiography
- If positive, can localize the source of bleed and increase the success of intervention
Whether a positive CTA should be followed with a colonoscopy or visceral angiography remains unclear. Studies show that positive CTAs increase the detection rate of stigmata of recent hemorrhage on colonoscopy. Positive CTAs can also identify a target for embolization by interventional radiology (IR). Though an important caveat is that the success rate of embolization is highest when performed within 90 minutes of a positive CTA. This highlights that if you have IR availability, it is critical to have clear communication, a well-defined protocol, and collaboration among disciplines (i.e., ED, medical team, GI, and IR).
At our institution, we have implemented a CTA-guided protocol for severe LGIB. Those with positive CTAs are referred immediately to IR for embolization. If the embolization is unsuccessful or CTA is negative, the patient will be planned for a non-urgent inpatient colonoscopy. However, our unpublished data and other studies have shown that the overall CTA positivity rates are only between 16-22%. Moreover, one randomized controlled trial comparing CTA versus colonoscopy as an initial test did not show any meaningful difference in clinical outcomes. Thus, the benefit of CTA and the best approach to positive CTAs remains in question.
Lastly, people often ask about the utility of RBC nuclear scans. While they can detect bleeds at a slower rate (as low as 0.1 mL/min) compared to CTA (at least 0.4 mL/min), there are many limitations. RBC scans take time, are not available 24-7, and cannot precisely localize the site of bleeding. Therefore, we rarely recommend them for LGIB.
Approach to Recurrent Diverticular Bleeding
Unfortunately, diverticular bleeding recurs in the hospital 14% of the time and up to 25% at 5 years. When this occurs, is it worthwhile to repeat another colonoscopy or CTA?
Given the lack of clear data, we have adopted a shared decision-making framework with patients. Oftentimes, these patients are older and have significant co-morbidities, and undergoing bowel preparation, anesthesia, and colonoscopy is not trivial. If the patient is stable and prior work-up has excluded pertinent alternative diagnoses other than diverticular bleeding, then we tell patients the chance of finding an intervenable lesion is low and opt for conservative management. Meanwhile, if the patient has persistent, hemodynamically significant bleeding, we recommend a CTA based on the rationale discussed previously.
The most important clinical decision may not be about scoping or obtaining a CTA – it is medication management. If they are taking NSAIDs, they should be discontinued. If antiplatelet or anticoagulation agents were held, they should be restarted promptly in individuals with significant thrombotic risk given studies showing that while rebleeding rates may increase, overall mortality decreases.
In summary, managing LGIB and altering its natural history with either endoscopic or radiographic means is challenging. More studies are needed to guide the optimal approach. Reassuringly, most bleeding self-resolves and patients have good clinical outcomes.
Dr. Lee is a resident physician at New York Presbyterian Weill Cornell Medical Center, New York, NY. Dr. Wan is associate professor of clinical medicine at Weill Cornell Medicine, New York, N.Y. They declare no conflicts of interest.
Lower Gastrointestinal Bleeding: An Interventional Radiologist’s Perspective
BY ZEYAD METWALLI, MD, FSIR
When colonoscopy fails to localize and/or stop lower gastrointestinal bleeding (LGIB), catheter angiography has been commonly employed as a tool for both diagnosis and treatment of bleeding with embolization. Nuclear medicine or CT imaging studies can serve as useful adjuncts for confirming active bleeding and localizing the site of bleeding prior to angiography, particularly if this information is not provided by colonoscopy. Provocative mesenteric angiography has also become increasingly popular as a troubleshooting technique in patients with initially negative angiography.
Localization of Lower Gastrointestinal Bleeding
Radionuclide technetium-99m-lableled red blood cell scintigraphy (RBCS), also known as tagged RBC scintigraphy, has been in use since the early 1980s for investigation of acute gastrointestinal bleeding. RBCS has a high sensitivity for detection of active bleeding with a theoretical ability to detect bleeding at rates as low as 0.04-0.2 mL/minute.
Imaging protocols vary but should include dynamic images, which may aid in localization of bleeding. The relatively long half-life of the tracer used for imaging allows for delayed imaging 12 to 24 hours after injection. This can be useful to confirm active bleeding, particularly when bleeding is intermittent and is not visible on initial images.
With the advent of computed tomography angiography (CTA), which continues to increase in speed, imaging quality and availability, the use of RBCS for evaluation of LGIB has declined. CTA is quicker to perform than RBCS and allows for detection of bleeding as well as accurate anatomic localization, which can guide interventions.
CTA provides a more comprehensive anatomic evaluation, which can aid in the diagnosis of a wide variety of intra-abdominal issues. Conversely, CTA may be less sensitive than RBCS for detection of slower acute bleeding, detecting bleeding at rates of 0.1-1 mL/min. In addition, intermittent bleeding which has temporarily stopped at the time of CTA may evade detection.
Lastly, CTA may not be appropriate in patients with impaired renal function due to risk of contrast-induced nephropathy, particularly in patients with acute kidney injury, which commonly afflicts hospitalized patients with LGIB. Prophylaxis with normal saline hydration should be employed aggressively in patients with impaired renal function, particularly when eGFR is less than 30 mL/minute. Iodinated contrast should be used judiciously in these patients.
In clinical practice, CTA and RBCS have a similar ability to confirm the presence or absence of clinically significant active gastrointestinal bleeding. Given the greater ability to rapidly localize the bleeding site with CTA, this is generally preferred over RBCS unless there is a contraindication to performing CTA, such as severe contrast allergy or high risk for development of contrast-induced nephropathy.
Role of Catheter Angiography and Embolization
Mesenteric angiography is a well-established technique for both detection and treatment of LGIB. Hemodynamic instability and need for packed RBC transfusion increases the likelihood of positive angiography. Limitations include reduced sensitivity for detection of bleeding slower than 0.5-1 mL/minute as well as the intermittent nature of LGIB, which will often resolve spontaneously. Angiography is variably successful in the literature with a diagnostic yield between 40-80%, which encompasses the rate of success in my own practice.
Once bleeding is identified, microcatheter placement within the feeding vessel as close as possible to the site of bleeding is important to ensure treatment efficacy and to limit risk of complications such as non-target embolization and bowel ischemia. Once the feeding vessel is selected with a microcatheter, embolization can be accomplished with a wide variety of tools including metallic coils, liquid embolic agents, and particles. In the treatment of LGIB, liquid embolic agents (e.g., n-butyl cyanoacrylate or NBCA, ethylene vinyl alcohol copolymer, etc.) and particles should be used judiciously as distal penetration increases the risk of bowel ischemia and procedure-related morbidity. For this reason, metallic coils are often preferred in the treatment of LGIB.
Although the source of bleeding is variable and may include diverticulosis, recent polypectomy, ulcer, tumor or angiodysplasia, the techniques employed are similar. Accurate and distal microcatheter selection is a key driver for successful embolization and minimizing the risk of bowel ischemia. Small intestinal bleeds can be challenging to treat due to the redundant supply of the arterial arcades supplying small bowel and may require occlusion of several branches to achieve hemostasis. This approach must be balanced with the risk of developing ischemia after embolization. Angiodysplasia, a less frequently encountered culprit of LGIB, may also be managed with selective embolization with many reports of successful treatment with liquid embolic agents such as NBCA mixed with ethiodized oil.
Provocative Mesenteric Angiography for Occult Bleeding
When initial angiography in a patient with suspected active LGIB is negative, provocative angiography can be considered to uncover an intermittent bleed. This may be particularly helpful in a patient where active bleeding is confirmed on a prior diagnostic test.
The approach to provocative mesenteric angiography varies by center, and a variety of agents have been used to provoke bleeding including heparin, vasodilators (i.e., nitroglycerin, verapamil, etc.) and thrombolytics (i.e., tPA), often in combination. Thrombolytics can be administered directly into the territory of interest (i.e., superior mesenteric or inferior mesenteric artery) while heparin may be administered systemically or directly into the catheterized artery. Reported success rates for provoking angiographically visible bleeding vary, but most larger series report a 40-50% success rate. The newly detected bleeding can then be treated with either embolization or surgery. A surgeon should be involved and available when provocative angiography is planned should bleeding fail to be controlled by embolization.
In summary, when colonoscopy fails to identify or control lower gastrointestinal bleeding (LGIB), imaging techniques such as RBCS and CTA play a crucial role in localizing active bleeding. While RBCS is highly sensitive, especially for intermittent or slow bleeding, CTA offers faster, more detailed anatomical information and is typically preferred unless contraindicated by renal issues or contrast allergies. Catheter-based mesenteric angiography is a well-established method for both diagnosing and treating LGIB, often using metallic coils to minimize complications like bowel ischemia. In cases where initial angiography is negative, provocative angiography – using agents like heparin or thrombolytics – may help unmask intermittent bleeding, allowing for targeted embolization or surgical intervention.
Dr. Metwalli is associate professor in the Department of Interventional Radiology, Division of Diagnostic Imaging, at The University of Texas MD Anderson Cancer Center, Houston, Texas. He declares no conflicts of interest.
Dear colleagues,
: What is the role and optimal timing of colonoscopy? How can we best utilize radiologic studies like CTA or tagged RBC scans? How should we manage patients with recurrent or intermittent bleeding that defies localization?
In this issue of Perspectives, Dr. David Wan, Dr. Fredella Lee, and Dr. Zeyad Metwalli offer their expert insights on these difficult questions. Dr. Wan, drawing on over 15 years of experience as a GI hospitalist, shares – along with his coauthor Dr. Lee – a pragmatic approach to LGIB based on clinical patterns, evolving data, and multidisciplinary collaboration. Dr. Metwalli provides the interventional radiologist’s perspective, highlighting how angiographic techniques can complement GI management and introducing novel IR strategies for patients with recurrent or elusive bleeding.
We hope their perspectives will offer valuable guidance for your practice. Join the conversation on X at @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.
Management of Lower Gastrointestinal Bleeds: GI Perspective
BY FREDELLA LEE, MD; DAVID WAN, MD
Acute lower gastrointestinal bleeding (LGIB) presents unique challenges. Much of this stems from the natural history of diverticular bleeding, the most common etiology of LGIB.
First, while bleeding can be severe, most will spontaneously stop. Second, despite our best efforts with imaging or colonoscopy, finding an intervenable lesion is rare. Third, LGIB has significant rates of rebleeding that are unpredictable.
While serving as a GI hospitalist for 15 years and after managing over 300 cases of LGIB, I often find myself frustrated and colonoscopy feels futile. So how can we rationally approach these patients? We will focus on three clinical questions to develop a framework for LGIB management.
- What is the role and timing for a colonoscopy?
- How do we best utilize radiologic tests?
- How can we prevent recurrent LGIB?
The Role of Colonoscopy
Traditionally, colonoscopy within 24 hours of presentation was recommended. This was based on retrospective cohort data showing higher endoscopic intervention rates and better clinical outcomes. However, this protocol requires patients to drink a significant volume of bowel preparation over a few hours (often requiring an NGT) to achieve clear rectal effluent. Moreover, one needs to mobilize a team (i.e., nurse, technician, anesthesiologist, and gastroenterologist), and find an appropriate location to scope (i.e., ED, ICU, or OR), Understandably, this is challenging, especially overnight. When the therapeutic yield is relatively low, this approach quickly loses enthusiasm.
Importantly, meta-analyses of the randomized controlled trials, have shown that urgent colonoscopies (<24 hours upon presentation), compared to elective colonoscopies (>24 hours upon presentation), do not improve clinical outcomes such as re-bleeding rates, transfusion requirements, mortality, or length of stay. In these studies, the endoscopic intervention rates were 17-34%, however, observational data shows rates of only 8%. In our practice, we will use a clear cap attachment device and water jet irrigation to increase the odds of detecting an active source of bleeding. Colonoscopy has a diagnostic yield of 95% – despite its low therapeutic yield; and while diverticular bleeds constitute up to 64% of cases, one does not want to miss colorectal cancer or other diagnoses. Regardless, there is generally no urgency to perform a colonoscopy. To quote a colleague, Dr. Elizabeth Ross, “there is no such thing as door-to-butt time.”
The Role of Radiology
Given the limits of colonoscopy, can radiographic tests such as computed tomography angiography (CTA) or tagged red blood cell (RBC) scan be helpful? Multiple studies have suggested using CTA as the initial diagnostic test. The advantages of CTAs are:
- Fast, readily available, and does not require a bowel preparation
- If negative, CTAs portend a good prognosis and make it highly unlikely to detect active extravasation on visceral angiography
- If positive, can localize the source of bleed and increase the success of intervention
Whether a positive CTA should be followed with a colonoscopy or visceral angiography remains unclear. Studies show that positive CTAs increase the detection rate of stigmata of recent hemorrhage on colonoscopy. Positive CTAs can also identify a target for embolization by interventional radiology (IR). Though an important caveat is that the success rate of embolization is highest when performed within 90 minutes of a positive CTA. This highlights that if you have IR availability, it is critical to have clear communication, a well-defined protocol, and collaboration among disciplines (i.e., ED, medical team, GI, and IR).
At our institution, we have implemented a CTA-guided protocol for severe LGIB. Those with positive CTAs are referred immediately to IR for embolization. If the embolization is unsuccessful or CTA is negative, the patient will be planned for a non-urgent inpatient colonoscopy. However, our unpublished data and other studies have shown that the overall CTA positivity rates are only between 16-22%. Moreover, one randomized controlled trial comparing CTA versus colonoscopy as an initial test did not show any meaningful difference in clinical outcomes. Thus, the benefit of CTA and the best approach to positive CTAs remains in question.
Lastly, people often ask about the utility of RBC nuclear scans. While they can detect bleeds at a slower rate (as low as 0.1 mL/min) compared to CTA (at least 0.4 mL/min), there are many limitations. RBC scans take time, are not available 24-7, and cannot precisely localize the site of bleeding. Therefore, we rarely recommend them for LGIB.
Approach to Recurrent Diverticular Bleeding
Unfortunately, diverticular bleeding recurs in the hospital 14% of the time and up to 25% at 5 years. When this occurs, is it worthwhile to repeat another colonoscopy or CTA?
Given the lack of clear data, we have adopted a shared decision-making framework with patients. Oftentimes, these patients are older and have significant co-morbidities, and undergoing bowel preparation, anesthesia, and colonoscopy is not trivial. If the patient is stable and prior work-up has excluded pertinent alternative diagnoses other than diverticular bleeding, then we tell patients the chance of finding an intervenable lesion is low and opt for conservative management. Meanwhile, if the patient has persistent, hemodynamically significant bleeding, we recommend a CTA based on the rationale discussed previously.
The most important clinical decision may not be about scoping or obtaining a CTA – it is medication management. If they are taking NSAIDs, they should be discontinued. If antiplatelet or anticoagulation agents were held, they should be restarted promptly in individuals with significant thrombotic risk given studies showing that while rebleeding rates may increase, overall mortality decreases.
In summary, managing LGIB and altering its natural history with either endoscopic or radiographic means is challenging. More studies are needed to guide the optimal approach. Reassuringly, most bleeding self-resolves and patients have good clinical outcomes.
Dr. Lee is a resident physician at New York Presbyterian Weill Cornell Medical Center, New York, NY. Dr. Wan is associate professor of clinical medicine at Weill Cornell Medicine, New York, N.Y. They declare no conflicts of interest.
Lower Gastrointestinal Bleeding: An Interventional Radiologist’s Perspective
BY ZEYAD METWALLI, MD, FSIR
When colonoscopy fails to localize and/or stop lower gastrointestinal bleeding (LGIB), catheter angiography has been commonly employed as a tool for both diagnosis and treatment of bleeding with embolization. Nuclear medicine or CT imaging studies can serve as useful adjuncts for confirming active bleeding and localizing the site of bleeding prior to angiography, particularly if this information is not provided by colonoscopy. Provocative mesenteric angiography has also become increasingly popular as a troubleshooting technique in patients with initially negative angiography.
Localization of Lower Gastrointestinal Bleeding
Radionuclide technetium-99m-lableled red blood cell scintigraphy (RBCS), also known as tagged RBC scintigraphy, has been in use since the early 1980s for investigation of acute gastrointestinal bleeding. RBCS has a high sensitivity for detection of active bleeding with a theoretical ability to detect bleeding at rates as low as 0.04-0.2 mL/minute.
Imaging protocols vary but should include dynamic images, which may aid in localization of bleeding. The relatively long half-life of the tracer used for imaging allows for delayed imaging 12 to 24 hours after injection. This can be useful to confirm active bleeding, particularly when bleeding is intermittent and is not visible on initial images.
With the advent of computed tomography angiography (CTA), which continues to increase in speed, imaging quality and availability, the use of RBCS for evaluation of LGIB has declined. CTA is quicker to perform than RBCS and allows for detection of bleeding as well as accurate anatomic localization, which can guide interventions.
CTA provides a more comprehensive anatomic evaluation, which can aid in the diagnosis of a wide variety of intra-abdominal issues. Conversely, CTA may be less sensitive than RBCS for detection of slower acute bleeding, detecting bleeding at rates of 0.1-1 mL/min. In addition, intermittent bleeding which has temporarily stopped at the time of CTA may evade detection.
Lastly, CTA may not be appropriate in patients with impaired renal function due to risk of contrast-induced nephropathy, particularly in patients with acute kidney injury, which commonly afflicts hospitalized patients with LGIB. Prophylaxis with normal saline hydration should be employed aggressively in patients with impaired renal function, particularly when eGFR is less than 30 mL/minute. Iodinated contrast should be used judiciously in these patients.
In clinical practice, CTA and RBCS have a similar ability to confirm the presence or absence of clinically significant active gastrointestinal bleeding. Given the greater ability to rapidly localize the bleeding site with CTA, this is generally preferred over RBCS unless there is a contraindication to performing CTA, such as severe contrast allergy or high risk for development of contrast-induced nephropathy.
Role of Catheter Angiography and Embolization
Mesenteric angiography is a well-established technique for both detection and treatment of LGIB. Hemodynamic instability and need for packed RBC transfusion increases the likelihood of positive angiography. Limitations include reduced sensitivity for detection of bleeding slower than 0.5-1 mL/minute as well as the intermittent nature of LGIB, which will often resolve spontaneously. Angiography is variably successful in the literature with a diagnostic yield between 40-80%, which encompasses the rate of success in my own practice.
Once bleeding is identified, microcatheter placement within the feeding vessel as close as possible to the site of bleeding is important to ensure treatment efficacy and to limit risk of complications such as non-target embolization and bowel ischemia. Once the feeding vessel is selected with a microcatheter, embolization can be accomplished with a wide variety of tools including metallic coils, liquid embolic agents, and particles. In the treatment of LGIB, liquid embolic agents (e.g., n-butyl cyanoacrylate or NBCA, ethylene vinyl alcohol copolymer, etc.) and particles should be used judiciously as distal penetration increases the risk of bowel ischemia and procedure-related morbidity. For this reason, metallic coils are often preferred in the treatment of LGIB.
Although the source of bleeding is variable and may include diverticulosis, recent polypectomy, ulcer, tumor or angiodysplasia, the techniques employed are similar. Accurate and distal microcatheter selection is a key driver for successful embolization and minimizing the risk of bowel ischemia. Small intestinal bleeds can be challenging to treat due to the redundant supply of the arterial arcades supplying small bowel and may require occlusion of several branches to achieve hemostasis. This approach must be balanced with the risk of developing ischemia after embolization. Angiodysplasia, a less frequently encountered culprit of LGIB, may also be managed with selective embolization with many reports of successful treatment with liquid embolic agents such as NBCA mixed with ethiodized oil.
Provocative Mesenteric Angiography for Occult Bleeding
When initial angiography in a patient with suspected active LGIB is negative, provocative angiography can be considered to uncover an intermittent bleed. This may be particularly helpful in a patient where active bleeding is confirmed on a prior diagnostic test.
The approach to provocative mesenteric angiography varies by center, and a variety of agents have been used to provoke bleeding including heparin, vasodilators (i.e., nitroglycerin, verapamil, etc.) and thrombolytics (i.e., tPA), often in combination. Thrombolytics can be administered directly into the territory of interest (i.e., superior mesenteric or inferior mesenteric artery) while heparin may be administered systemically or directly into the catheterized artery. Reported success rates for provoking angiographically visible bleeding vary, but most larger series report a 40-50% success rate. The newly detected bleeding can then be treated with either embolization or surgery. A surgeon should be involved and available when provocative angiography is planned should bleeding fail to be controlled by embolization.
In summary, when colonoscopy fails to identify or control lower gastrointestinal bleeding (LGIB), imaging techniques such as RBCS and CTA play a crucial role in localizing active bleeding. While RBCS is highly sensitive, especially for intermittent or slow bleeding, CTA offers faster, more detailed anatomical information and is typically preferred unless contraindicated by renal issues or contrast allergies. Catheter-based mesenteric angiography is a well-established method for both diagnosing and treating LGIB, often using metallic coils to minimize complications like bowel ischemia. In cases where initial angiography is negative, provocative angiography – using agents like heparin or thrombolytics – may help unmask intermittent bleeding, allowing for targeted embolization or surgical intervention.
Dr. Metwalli is associate professor in the Department of Interventional Radiology, Division of Diagnostic Imaging, at The University of Texas MD Anderson Cancer Center, Houston, Texas. He declares no conflicts of interest.
Improving Care for Patients from Historically Minoritized and Marginalized Communities with Disorders of Gut-Brain Interaction
Introduction: Cases
Patient 1: A 57-year-old man with post-prandial distress variant functional dyspepsia (FD) was recommended to start nortriptyline. He previously established primary care with a physician he met at a barbershop health fair in Harlem, who referred him for specialty evaluation. Today, he presents for follow-up and reports he did not take this medication because he heard it is an antidepressant. How would you counsel him?
Patient 2: A 61-year-old woman was previously diagnosed with mixed variant irritable bowel syndrome (IBS-M). Her symptoms have not significantly changed. Her prior workup has been reassuring and consistent with IBS-M. Despite this, the patient pushes to repeat a colonoscopy, fearful that something is being missed or that she is not being offered care because of her undocumented status. How do you respond?
Patient 3: A 36-year-old man is followed for the management of generalized anxiety disorder and functional heartburn. He was started on low-dose amitriptyline with some benefit, but follow-up has been sporadic. On further discussion, he reports financial stressors, time barriers, and difficulty scheduling a meeting with his union representative for work accommodations as he lives in a more rural community. How do you reply?
Patient 4: A 74-year-old man with Parkinson’s disease who uses a wheelchair has functional constipation that is well controlled on his current regimen. He has never undergone colon cancer screening. He occasionally notices blood in his stool, so a colonoscopy was recommended to confirm that his hematochezia reflects functional constipation complicated by hemorrhoids. He is concerned about the bowel preparation required for a colonoscopy given his limited mobility, as his insurance does not cover assistance at home. He does not have family members to help him. How can you assist him?
Social determinants of health, health disparities, and DGBIs
Social determinants of health affect all aspects of patient care, with an increasing body of published work looking at potential disparities in organ-based and structural diseases.1,2,3,4 However, little has been done to explore their influence on disorders of gut-brain interaction or DGBIs.
. As DGBIs cannot be diagnosed with a single laboratory or endoscopic test, the patient history is of the utmost importance and physician-patient rapport is paramount in their treatment. Such rapport may be more difficult to establish in patients coming from historically marginalized and minoritized communities who may be distrustful of healthcare as an institution of (discriminatory) power.
Potential DGBI management pitfalls in historically marginalized or minoritized communities
For racial and ethnic minorities in the United States, disparities in healthcare take on many forms. People from racial and ethnic minority communities are less likely to receive a gastroenterology consultation and those with IBS are more likely to undergo procedures as compared to White patients with IBS.6 Implicit bias may lead to fewer specialist referrals, and specialty care may be limited or unavailable in some areas. Patients may prefer seeing providers in their own community, with whom they share racial or ethnic identities, which could lead to fewer referrals to specialists outside of the community.
Historical discrimination contributes to a lack of trust in healthcare professionals, which may lead patients to favor more objective diagnostics such as endoscopy or view being counseled against invasive procedures as having necessary care denied. Due to a broader cultural stigma surrounding mental illness, patients may be more hesitant to utilize neuromodulators, which have historically been used for psychiatric diagnoses, as it may lead them to conflate their GI illness with mental illness.7,8
Since DGBIs cannot be diagnosed with a single test or managed with a single treatment modality, providing excellent care for patients with DGBIs requires clear communication. For patients with limited English proficiency (LEP), access to high-quality language assistance is the foundation of comprehensive care. Interpreter use (or lack thereof) may limit the ability to obtain a complete and accurate clinical history, which can lead to fewer referrals to specialists and increased reliance on endoscopic evaluations that may not be clinically indicated.
These language barriers affect patients on many levels – in their ability to understand instructions for medication administration, preparation for procedures, and return precautions – which may ultimately lead to poorer responses to therapy or delays in care. LEP alone is broadly associated with fewer referrals for outpatient follow-up, adverse health outcomes and complications, and longer hospital stays.9 These disparities can be mitigated by investing in high-quality interpreter services, providing instructions and forms in multiple languages, and engaging the patient’s family and social supports according to their preferences.
People experiencing poverty (urban and rural) face challenges across multiple domains including access to healthcare, health insurance, stable housing and employment, and more. Many patients seek care at federally qualified health centers, which may face greater difficulties coordinating care with external gastroenterologists.10
Insurance barriers limit access to essential medications, tests, and procedures, and create delays in establishing care with specialists. Significant psychological stress and higher rates of comorbid anxiety and depression contribute to increased IBS severity.11 Financial limitations may limit dietary choices, which can further exacerbate DGBI symptoms. Long work hours with limited flexibility may prohibit them from presenting for regular follow-ups and establishing advanced DGBI care such as with a dietitian or psychologist.
Patients with disabilities face many of the health inequities previously discussed, as well as additional challenges with physical accessibility, transportation, exclusion from education and employment, discrimination, and stigma. Higher prevalence of comorbid mental illness and higher rates of intimate partner violence and interpersonal violence all contribute to DGBI severity and challenges with access to care.12,13 Patients with disabilities may struggle to arrive at appointments, maneuver through the building or exam room, and ultimately follow recommended care plans.
How to approach DGBIs in historically marginalized and minoritized communities
Returning to the patients from the introduction, how would you counsel each of them?
Patient 1: We can discuss with the patient how nortriptyline and other typical antidepressants can and often are used for indications other than depression. These medications modify centrally-mediated pain signaling and many patients with functional dyspepsia experience a significant benefit. It is critical to build on the rapport that was established at the community health outreach event and to explore the patient’s concerns thoroughly.
Patient 2: We would begin by inquiring about her underlying fears associated with her symptoms and seek to understand her goals for repeat intervention. We can review the risks of endoscopy and shift the focus to improving her symptoms. If we can improve her bowel habits or her pain, her desire for further interventions may lessen.
Patient 3: It will be important to work within the realistic time and monetary constraints in this patient’s life. We can validate him and the challenges he is facing, provide positive reinforcement for the progress he has made so far, and avoid disparaging him for the aspects of the treatment plan he has been unable to follow through with. As he reported a benefit from amitriptyline, we can consider increasing his dose as a feasible next step.
Patient 4: We can encourage the patient to discuss with his primary care physician how they may be able to coordinate an inpatient admission for colonoscopy preparation. Given his co-morbidities, this avenue will provide him dedicated support to help him adequately prep to ensure a higher quality examination and limit the need for repeat procedures.
DGBI care in historically marginalized and minoritized communities: A call to action
Understanding cultural differences and existing disparities in care is essential to improving care for patients from historically minoritized communities with DGBIs. Motivational interviewing and shared decision-making, with acknowledgment of social and cultural differences, allow us to work together with patients and their support systems to set and achieve feasible goals.14
To address known health disparities, offices can take steps to ensure the accessibility of language, forms, physical space, providers, and care teams. Providing culturally sensitive care and lowering barriers to care are the first steps to effecting meaningful change for patients with DGBIs from historically minoritized communities.
Dr. Yu is based at Division of Gastroenterology and Hepatology, Boston Medical Center and Boston University, both in Boston, Massachusetts. Dr. Dimino and Dr. Vélez are based at the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, both in Boston, Massachusetts. Dr. Yu, Dr. Dimino, and Dr. Vélez do not have any conflicts of interest for this article.
Additional Online Resources
Form Accessibility
- Intake Form Guidance for Providers
- Making Your Clinic Welcoming to LGBTQ Patients
- Transgender data collection in the electronic health record: Current concepts and issues
Language Accessibility
Physical Accessibility
- Access to Medical Care for Individuals with Mobility Disabilities
- Making your medical office accessible
References
1. Zavala VA, et al. Cancer health disparities in racial/ethnic minorities in the United States. Br J Cancer. 2021 Jan. doi: 10.1038/s41416-020-01038-6.
2. Kardashian A, et al. Health disparities in chronic liver disease. Hepatology. 2023 Apr. doi: 10.1002/hep.32743.
3. Nephew LD, Serper M. Racial, Gender, and Socioeconomic Disparities in Liver Transplantation. Liver Transpl. 2021 Jun. doi: 10.1002/lt.25996.
4. Anyane-Yeboa A, et al. The Impact of the Social Determinants of Health on Disparities in Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2022 Nov. doi: 10.1016/j.cgh.2022.03.011.
5. Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb. doi: 10.1053/j.gastro.2016.02.032.
6. Silvernale C, et al. Racial disparity in healthcare utilization among patients with Irritable Bowel Syndrome: results from a multicenter cohort. Neurogastroenterol Motil. 2021 May. doi: 10.1111/nmo.14039.
7. Hearn M, et al. Stigma and irritable bowel syndrome: a taboo subject? Lancet Gastroenterol Hepatol. 2020 Jun. doi: 10.1016/S2468-1253(19)30348-6.
8. Yan XJ, et al. The impact of stigma on medication adherence in patients with functional dyspepsia. Neurogastroenterol Motil. 2021 Feb. doi: 10.1111/nmo.13956.
9. Twersky SE, et al. The Impact of Limited English Proficiency on Healthcare Access and Outcomes in the U.S.: A Scoping Review. Healthcare (Basel). 2024 Jan. doi: 10.3390/healthcare12030364.
10. Bayly JE, et al. Limited English proficiency and reported receipt of colorectal cancer screening among adults 45-75 in 2019 and 2021. Prev Med Rep. 2024 Feb. doi: 10.1016/j.pmedr.2024.102638.
11. Cheng K, et al. Epidemiology of Irritable Bowel Syndrome in a Large Academic Safety-Net Hospital. J Clin Med. 2024 Feb. doi: 10.3390/jcm13051314.
12. Breiding MJ, Armour BS. The association between disability and intimate partner violence in the United States. Ann Epidemiol. 2015 Jun. doi: 10.1016/j.annepidem.2015.03.017.
13. Mitra M, et al. Prevalence and characteristics of sexual violence against men with disabilities. Am J Prev Med. 2016 Mar. doi: 10.1016/j.amepre.2015.07.030.
14. Bahafzallah L, et al. Motivational Interviewing in Ethnic Populations. J Immigr Minor Health. 2020 Aug. doi: 10.1007/s10903-019-00940-3.
Introduction: Cases
Patient 1: A 57-year-old man with post-prandial distress variant functional dyspepsia (FD) was recommended to start nortriptyline. He previously established primary care with a physician he met at a barbershop health fair in Harlem, who referred him for specialty evaluation. Today, he presents for follow-up and reports he did not take this medication because he heard it is an antidepressant. How would you counsel him?
Patient 2: A 61-year-old woman was previously diagnosed with mixed variant irritable bowel syndrome (IBS-M). Her symptoms have not significantly changed. Her prior workup has been reassuring and consistent with IBS-M. Despite this, the patient pushes to repeat a colonoscopy, fearful that something is being missed or that she is not being offered care because of her undocumented status. How do you respond?
Patient 3: A 36-year-old man is followed for the management of generalized anxiety disorder and functional heartburn. He was started on low-dose amitriptyline with some benefit, but follow-up has been sporadic. On further discussion, he reports financial stressors, time barriers, and difficulty scheduling a meeting with his union representative for work accommodations as he lives in a more rural community. How do you reply?
Patient 4: A 74-year-old man with Parkinson’s disease who uses a wheelchair has functional constipation that is well controlled on his current regimen. He has never undergone colon cancer screening. He occasionally notices blood in his stool, so a colonoscopy was recommended to confirm that his hematochezia reflects functional constipation complicated by hemorrhoids. He is concerned about the bowel preparation required for a colonoscopy given his limited mobility, as his insurance does not cover assistance at home. He does not have family members to help him. How can you assist him?
Social determinants of health, health disparities, and DGBIs
Social determinants of health affect all aspects of patient care, with an increasing body of published work looking at potential disparities in organ-based and structural diseases.1,2,3,4 However, little has been done to explore their influence on disorders of gut-brain interaction or DGBIs.
. As DGBIs cannot be diagnosed with a single laboratory or endoscopic test, the patient history is of the utmost importance and physician-patient rapport is paramount in their treatment. Such rapport may be more difficult to establish in patients coming from historically marginalized and minoritized communities who may be distrustful of healthcare as an institution of (discriminatory) power.
Potential DGBI management pitfalls in historically marginalized or minoritized communities
For racial and ethnic minorities in the United States, disparities in healthcare take on many forms. People from racial and ethnic minority communities are less likely to receive a gastroenterology consultation and those with IBS are more likely to undergo procedures as compared to White patients with IBS.6 Implicit bias may lead to fewer specialist referrals, and specialty care may be limited or unavailable in some areas. Patients may prefer seeing providers in their own community, with whom they share racial or ethnic identities, which could lead to fewer referrals to specialists outside of the community.
Historical discrimination contributes to a lack of trust in healthcare professionals, which may lead patients to favor more objective diagnostics such as endoscopy or view being counseled against invasive procedures as having necessary care denied. Due to a broader cultural stigma surrounding mental illness, patients may be more hesitant to utilize neuromodulators, which have historically been used for psychiatric diagnoses, as it may lead them to conflate their GI illness with mental illness.7,8
Since DGBIs cannot be diagnosed with a single test or managed with a single treatment modality, providing excellent care for patients with DGBIs requires clear communication. For patients with limited English proficiency (LEP), access to high-quality language assistance is the foundation of comprehensive care. Interpreter use (or lack thereof) may limit the ability to obtain a complete and accurate clinical history, which can lead to fewer referrals to specialists and increased reliance on endoscopic evaluations that may not be clinically indicated.
These language barriers affect patients on many levels – in their ability to understand instructions for medication administration, preparation for procedures, and return precautions – which may ultimately lead to poorer responses to therapy or delays in care. LEP alone is broadly associated with fewer referrals for outpatient follow-up, adverse health outcomes and complications, and longer hospital stays.9 These disparities can be mitigated by investing in high-quality interpreter services, providing instructions and forms in multiple languages, and engaging the patient’s family and social supports according to their preferences.
People experiencing poverty (urban and rural) face challenges across multiple domains including access to healthcare, health insurance, stable housing and employment, and more. Many patients seek care at federally qualified health centers, which may face greater difficulties coordinating care with external gastroenterologists.10
Insurance barriers limit access to essential medications, tests, and procedures, and create delays in establishing care with specialists. Significant psychological stress and higher rates of comorbid anxiety and depression contribute to increased IBS severity.11 Financial limitations may limit dietary choices, which can further exacerbate DGBI symptoms. Long work hours with limited flexibility may prohibit them from presenting for regular follow-ups and establishing advanced DGBI care such as with a dietitian or psychologist.
Patients with disabilities face many of the health inequities previously discussed, as well as additional challenges with physical accessibility, transportation, exclusion from education and employment, discrimination, and stigma. Higher prevalence of comorbid mental illness and higher rates of intimate partner violence and interpersonal violence all contribute to DGBI severity and challenges with access to care.12,13 Patients with disabilities may struggle to arrive at appointments, maneuver through the building or exam room, and ultimately follow recommended care plans.
How to approach DGBIs in historically marginalized and minoritized communities
Returning to the patients from the introduction, how would you counsel each of them?
Patient 1: We can discuss with the patient how nortriptyline and other typical antidepressants can and often are used for indications other than depression. These medications modify centrally-mediated pain signaling and many patients with functional dyspepsia experience a significant benefit. It is critical to build on the rapport that was established at the community health outreach event and to explore the patient’s concerns thoroughly.
Patient 2: We would begin by inquiring about her underlying fears associated with her symptoms and seek to understand her goals for repeat intervention. We can review the risks of endoscopy and shift the focus to improving her symptoms. If we can improve her bowel habits or her pain, her desire for further interventions may lessen.
Patient 3: It will be important to work within the realistic time and monetary constraints in this patient’s life. We can validate him and the challenges he is facing, provide positive reinforcement for the progress he has made so far, and avoid disparaging him for the aspects of the treatment plan he has been unable to follow through with. As he reported a benefit from amitriptyline, we can consider increasing his dose as a feasible next step.
Patient 4: We can encourage the patient to discuss with his primary care physician how they may be able to coordinate an inpatient admission for colonoscopy preparation. Given his co-morbidities, this avenue will provide him dedicated support to help him adequately prep to ensure a higher quality examination and limit the need for repeat procedures.
DGBI care in historically marginalized and minoritized communities: A call to action
Understanding cultural differences and existing disparities in care is essential to improving care for patients from historically minoritized communities with DGBIs. Motivational interviewing and shared decision-making, with acknowledgment of social and cultural differences, allow us to work together with patients and their support systems to set and achieve feasible goals.14
To address known health disparities, offices can take steps to ensure the accessibility of language, forms, physical space, providers, and care teams. Providing culturally sensitive care and lowering barriers to care are the first steps to effecting meaningful change for patients with DGBIs from historically minoritized communities.
Dr. Yu is based at Division of Gastroenterology and Hepatology, Boston Medical Center and Boston University, both in Boston, Massachusetts. Dr. Dimino and Dr. Vélez are based at the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, both in Boston, Massachusetts. Dr. Yu, Dr. Dimino, and Dr. Vélez do not have any conflicts of interest for this article.
Additional Online Resources
Form Accessibility
- Intake Form Guidance for Providers
- Making Your Clinic Welcoming to LGBTQ Patients
- Transgender data collection in the electronic health record: Current concepts and issues
Language Accessibility
Physical Accessibility
- Access to Medical Care for Individuals with Mobility Disabilities
- Making your medical office accessible
References
1. Zavala VA, et al. Cancer health disparities in racial/ethnic minorities in the United States. Br J Cancer. 2021 Jan. doi: 10.1038/s41416-020-01038-6.
2. Kardashian A, et al. Health disparities in chronic liver disease. Hepatology. 2023 Apr. doi: 10.1002/hep.32743.
3. Nephew LD, Serper M. Racial, Gender, and Socioeconomic Disparities in Liver Transplantation. Liver Transpl. 2021 Jun. doi: 10.1002/lt.25996.
4. Anyane-Yeboa A, et al. The Impact of the Social Determinants of Health on Disparities in Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2022 Nov. doi: 10.1016/j.cgh.2022.03.011.
5. Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb. doi: 10.1053/j.gastro.2016.02.032.
6. Silvernale C, et al. Racial disparity in healthcare utilization among patients with Irritable Bowel Syndrome: results from a multicenter cohort. Neurogastroenterol Motil. 2021 May. doi: 10.1111/nmo.14039.
7. Hearn M, et al. Stigma and irritable bowel syndrome: a taboo subject? Lancet Gastroenterol Hepatol. 2020 Jun. doi: 10.1016/S2468-1253(19)30348-6.
8. Yan XJ, et al. The impact of stigma on medication adherence in patients with functional dyspepsia. Neurogastroenterol Motil. 2021 Feb. doi: 10.1111/nmo.13956.
9. Twersky SE, et al. The Impact of Limited English Proficiency on Healthcare Access and Outcomes in the U.S.: A Scoping Review. Healthcare (Basel). 2024 Jan. doi: 10.3390/healthcare12030364.
10. Bayly JE, et al. Limited English proficiency and reported receipt of colorectal cancer screening among adults 45-75 in 2019 and 2021. Prev Med Rep. 2024 Feb. doi: 10.1016/j.pmedr.2024.102638.
11. Cheng K, et al. Epidemiology of Irritable Bowel Syndrome in a Large Academic Safety-Net Hospital. J Clin Med. 2024 Feb. doi: 10.3390/jcm13051314.
12. Breiding MJ, Armour BS. The association between disability and intimate partner violence in the United States. Ann Epidemiol. 2015 Jun. doi: 10.1016/j.annepidem.2015.03.017.
13. Mitra M, et al. Prevalence and characteristics of sexual violence against men with disabilities. Am J Prev Med. 2016 Mar. doi: 10.1016/j.amepre.2015.07.030.
14. Bahafzallah L, et al. Motivational Interviewing in Ethnic Populations. J Immigr Minor Health. 2020 Aug. doi: 10.1007/s10903-019-00940-3.
Introduction: Cases
Patient 1: A 57-year-old man with post-prandial distress variant functional dyspepsia (FD) was recommended to start nortriptyline. He previously established primary care with a physician he met at a barbershop health fair in Harlem, who referred him for specialty evaluation. Today, he presents for follow-up and reports he did not take this medication because he heard it is an antidepressant. How would you counsel him?
Patient 2: A 61-year-old woman was previously diagnosed with mixed variant irritable bowel syndrome (IBS-M). Her symptoms have not significantly changed. Her prior workup has been reassuring and consistent with IBS-M. Despite this, the patient pushes to repeat a colonoscopy, fearful that something is being missed or that she is not being offered care because of her undocumented status. How do you respond?
Patient 3: A 36-year-old man is followed for the management of generalized anxiety disorder and functional heartburn. He was started on low-dose amitriptyline with some benefit, but follow-up has been sporadic. On further discussion, he reports financial stressors, time barriers, and difficulty scheduling a meeting with his union representative for work accommodations as he lives in a more rural community. How do you reply?
Patient 4: A 74-year-old man with Parkinson’s disease who uses a wheelchair has functional constipation that is well controlled on his current regimen. He has never undergone colon cancer screening. He occasionally notices blood in his stool, so a colonoscopy was recommended to confirm that his hematochezia reflects functional constipation complicated by hemorrhoids. He is concerned about the bowel preparation required for a colonoscopy given his limited mobility, as his insurance does not cover assistance at home. He does not have family members to help him. How can you assist him?
Social determinants of health, health disparities, and DGBIs
Social determinants of health affect all aspects of patient care, with an increasing body of published work looking at potential disparities in organ-based and structural diseases.1,2,3,4 However, little has been done to explore their influence on disorders of gut-brain interaction or DGBIs.
. As DGBIs cannot be diagnosed with a single laboratory or endoscopic test, the patient history is of the utmost importance and physician-patient rapport is paramount in their treatment. Such rapport may be more difficult to establish in patients coming from historically marginalized and minoritized communities who may be distrustful of healthcare as an institution of (discriminatory) power.
Potential DGBI management pitfalls in historically marginalized or minoritized communities
For racial and ethnic minorities in the United States, disparities in healthcare take on many forms. People from racial and ethnic minority communities are less likely to receive a gastroenterology consultation and those with IBS are more likely to undergo procedures as compared to White patients with IBS.6 Implicit bias may lead to fewer specialist referrals, and specialty care may be limited or unavailable in some areas. Patients may prefer seeing providers in their own community, with whom they share racial or ethnic identities, which could lead to fewer referrals to specialists outside of the community.
Historical discrimination contributes to a lack of trust in healthcare professionals, which may lead patients to favor more objective diagnostics such as endoscopy or view being counseled against invasive procedures as having necessary care denied. Due to a broader cultural stigma surrounding mental illness, patients may be more hesitant to utilize neuromodulators, which have historically been used for psychiatric diagnoses, as it may lead them to conflate their GI illness with mental illness.7,8
Since DGBIs cannot be diagnosed with a single test or managed with a single treatment modality, providing excellent care for patients with DGBIs requires clear communication. For patients with limited English proficiency (LEP), access to high-quality language assistance is the foundation of comprehensive care. Interpreter use (or lack thereof) may limit the ability to obtain a complete and accurate clinical history, which can lead to fewer referrals to specialists and increased reliance on endoscopic evaluations that may not be clinically indicated.
These language barriers affect patients on many levels – in their ability to understand instructions for medication administration, preparation for procedures, and return precautions – which may ultimately lead to poorer responses to therapy or delays in care. LEP alone is broadly associated with fewer referrals for outpatient follow-up, adverse health outcomes and complications, and longer hospital stays.9 These disparities can be mitigated by investing in high-quality interpreter services, providing instructions and forms in multiple languages, and engaging the patient’s family and social supports according to their preferences.
People experiencing poverty (urban and rural) face challenges across multiple domains including access to healthcare, health insurance, stable housing and employment, and more. Many patients seek care at federally qualified health centers, which may face greater difficulties coordinating care with external gastroenterologists.10
Insurance barriers limit access to essential medications, tests, and procedures, and create delays in establishing care with specialists. Significant psychological stress and higher rates of comorbid anxiety and depression contribute to increased IBS severity.11 Financial limitations may limit dietary choices, which can further exacerbate DGBI symptoms. Long work hours with limited flexibility may prohibit them from presenting for regular follow-ups and establishing advanced DGBI care such as with a dietitian or psychologist.
Patients with disabilities face many of the health inequities previously discussed, as well as additional challenges with physical accessibility, transportation, exclusion from education and employment, discrimination, and stigma. Higher prevalence of comorbid mental illness and higher rates of intimate partner violence and interpersonal violence all contribute to DGBI severity and challenges with access to care.12,13 Patients with disabilities may struggle to arrive at appointments, maneuver through the building or exam room, and ultimately follow recommended care plans.
How to approach DGBIs in historically marginalized and minoritized communities
Returning to the patients from the introduction, how would you counsel each of them?
Patient 1: We can discuss with the patient how nortriptyline and other typical antidepressants can and often are used for indications other than depression. These medications modify centrally-mediated pain signaling and many patients with functional dyspepsia experience a significant benefit. It is critical to build on the rapport that was established at the community health outreach event and to explore the patient’s concerns thoroughly.
Patient 2: We would begin by inquiring about her underlying fears associated with her symptoms and seek to understand her goals for repeat intervention. We can review the risks of endoscopy and shift the focus to improving her symptoms. If we can improve her bowel habits or her pain, her desire for further interventions may lessen.
Patient 3: It will be important to work within the realistic time and monetary constraints in this patient’s life. We can validate him and the challenges he is facing, provide positive reinforcement for the progress he has made so far, and avoid disparaging him for the aspects of the treatment plan he has been unable to follow through with. As he reported a benefit from amitriptyline, we can consider increasing his dose as a feasible next step.
Patient 4: We can encourage the patient to discuss with his primary care physician how they may be able to coordinate an inpatient admission for colonoscopy preparation. Given his co-morbidities, this avenue will provide him dedicated support to help him adequately prep to ensure a higher quality examination and limit the need for repeat procedures.
DGBI care in historically marginalized and minoritized communities: A call to action
Understanding cultural differences and existing disparities in care is essential to improving care for patients from historically minoritized communities with DGBIs. Motivational interviewing and shared decision-making, with acknowledgment of social and cultural differences, allow us to work together with patients and their support systems to set and achieve feasible goals.14
To address known health disparities, offices can take steps to ensure the accessibility of language, forms, physical space, providers, and care teams. Providing culturally sensitive care and lowering barriers to care are the first steps to effecting meaningful change for patients with DGBIs from historically minoritized communities.
Dr. Yu is based at Division of Gastroenterology and Hepatology, Boston Medical Center and Boston University, both in Boston, Massachusetts. Dr. Dimino and Dr. Vélez are based at the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, both in Boston, Massachusetts. Dr. Yu, Dr. Dimino, and Dr. Vélez do not have any conflicts of interest for this article.
Additional Online Resources
Form Accessibility
- Intake Form Guidance for Providers
- Making Your Clinic Welcoming to LGBTQ Patients
- Transgender data collection in the electronic health record: Current concepts and issues
Language Accessibility
Physical Accessibility
- Access to Medical Care for Individuals with Mobility Disabilities
- Making your medical office accessible
References
1. Zavala VA, et al. Cancer health disparities in racial/ethnic minorities in the United States. Br J Cancer. 2021 Jan. doi: 10.1038/s41416-020-01038-6.
2. Kardashian A, et al. Health disparities in chronic liver disease. Hepatology. 2023 Apr. doi: 10.1002/hep.32743.
3. Nephew LD, Serper M. Racial, Gender, and Socioeconomic Disparities in Liver Transplantation. Liver Transpl. 2021 Jun. doi: 10.1002/lt.25996.
4. Anyane-Yeboa A, et al. The Impact of the Social Determinants of Health on Disparities in Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2022 Nov. doi: 10.1016/j.cgh.2022.03.011.
5. Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb. doi: 10.1053/j.gastro.2016.02.032.
6. Silvernale C, et al. Racial disparity in healthcare utilization among patients with Irritable Bowel Syndrome: results from a multicenter cohort. Neurogastroenterol Motil. 2021 May. doi: 10.1111/nmo.14039.
7. Hearn M, et al. Stigma and irritable bowel syndrome: a taboo subject? Lancet Gastroenterol Hepatol. 2020 Jun. doi: 10.1016/S2468-1253(19)30348-6.
8. Yan XJ, et al. The impact of stigma on medication adherence in patients with functional dyspepsia. Neurogastroenterol Motil. 2021 Feb. doi: 10.1111/nmo.13956.
9. Twersky SE, et al. The Impact of Limited English Proficiency on Healthcare Access and Outcomes in the U.S.: A Scoping Review. Healthcare (Basel). 2024 Jan. doi: 10.3390/healthcare12030364.
10. Bayly JE, et al. Limited English proficiency and reported receipt of colorectal cancer screening among adults 45-75 in 2019 and 2021. Prev Med Rep. 2024 Feb. doi: 10.1016/j.pmedr.2024.102638.
11. Cheng K, et al. Epidemiology of Irritable Bowel Syndrome in a Large Academic Safety-Net Hospital. J Clin Med. 2024 Feb. doi: 10.3390/jcm13051314.
12. Breiding MJ, Armour BS. The association between disability and intimate partner violence in the United States. Ann Epidemiol. 2015 Jun. doi: 10.1016/j.annepidem.2015.03.017.
13. Mitra M, et al. Prevalence and characteristics of sexual violence against men with disabilities. Am J Prev Med. 2016 Mar. doi: 10.1016/j.amepre.2015.07.030.
14. Bahafzallah L, et al. Motivational Interviewing in Ethnic Populations. J Immigr Minor Health. 2020 Aug. doi: 10.1007/s10903-019-00940-3.
Walnuts Cut Gut Permeability in Obesity
, a small study showed.
“Less than 10% of adults are meeting their fiber needs each day, and walnuts are a source of dietary fiber, which helps nourish the gut microbiota,” study coauthor Hannah Holscher, PhD, RD, associate professor of nutrition at the University of Illinois at Urbana-Champaign, told GI & Hepatology News.
Holscher and her colleagues previously conducted a study on the effects of walnut consumption on the human intestinal microbiota “and found interesting results,” she said. Among 18 healthy men and women with a mean age of 53 years, “walnuts enriched intestinal microorganisms, including Roseburia that provide important gut-health promoting attributes, like short-chain fatty acid production. We also saw lower proinflammatory secondary bile acid concentrations in individuals that ate walnuts.”
The current study, presented at NUTRITION 2025 in Orlando, Florida, found similar benefits among 30 adults with obesity but without diabetes or gastrointestinal disease.
Walnut Halves, Walnut Oil, Corn Oil — Compared
The researchers aimed to determine the impact of walnut consumption on the gut microbiome, serum and fecal bile acid profiles, systemic inflammation, and oral glucose tolerance to a mixed-meal challenge.
Participants were enrolled in a randomized, controlled, crossover, complete feeding trial with three 3-week conditions, each identical except for walnut halves (WH), walnut oil (WO), or corn oil (CO) in the diet. A 3-week washout separated each condition.
“This was a fully controlled dietary feeding intervention,” Holscher said. “We provided their breakfast, lunch, snacks and dinners — all of their foods and beverages during the three dietary intervention periods that lasted for 3 weeks each. Their base diet consisted of typical American foods that you would find in a grocery store in central Illinois.”
Fecal samples were collected on days 18-20. On day 20, participants underwent a 6-hour mixed-meal tolerance test (75 g glucose + treatment) with a fasting blood draw followed by blood sampling every 30 minutes.
The fecal microbiome and microbiota were assessed using metagenomic and amplicon sequencing, respectively. Fecal microbial metabolites were quantified using gas chromatography-mass spectrometry.
Blood glucose, insulin, and inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha, C-reactive protein, and lipopolysaccharide-binding protein) were quantified. Fecal and circulating bile acids were measured via liquid chromatography tandem mass spectrometry.
Gut permeability was assessed by quantifying 24-hour urinary excretion of orally ingested sucralose and erythritol on day 21.
Linear mixed-effects models and repeated measures ANOVA were used for the statistical analysis.
The team found that Roseburia spp were greatest following WH (3.9%) vs WO (1.6) and CO (1.9); Lachnospiraceae UCG-001 and UCG-004 were also greatest with WH vs WO and CO.
WH fecal isobutyrate concentrations (5.41 µmol/g) were lower than WO (7.17 µmol/g) and CO (7.77). Similarly, fecal isovalerate concentrations were lowest with WH (7.84 µmol/g) vs WO (10.3µmol/g) and CO (11.6 µmol/g).
In contrast, indoles were highest in WH (36.8 µmol/g) vs WO (6.78 µmol/g) and CO (8.67µmol/g).
No differences in glucose concentrations were seen among groups. The 2-hour area under the curve (AUC) for insulin was lower with WH (469 µIU/mL/min) and WO (494) vs CO (604 µIU/mL/min).
The 4-hour AUC for glycolithocholic acid was lower with WH vs WO and CO. Furthermore, sucralose recovery was lowest following WH (10.5) vs WO (14.3) and CO (14.6).
“Our current efforts are focused on understanding connections between plasma bile acids and glycemic control (ie, blood glucose and insulin concentrations),” Holscher said. “We are also interested in studying individualized or personalized responses, since people had different magnitudes of responses.”
In addition, she said, “as the gut microbiome is one of the factors that can underpin the physiological response to the diet, we are interested in determining if there are microbial signatures that are predictive of glycemic control.”
Because the research is still in the early stages, at this point, Holscher simply encourages people to eat a variety of fruits, vegetables, whole grains, legumes and nuts to meet their daily fiber recommendations and support their gut microbiome.
This study was funded by a USDA NIFA grant. No competing interests were reported.
A version of this article appeared on Medscape.com .
, a small study showed.
“Less than 10% of adults are meeting their fiber needs each day, and walnuts are a source of dietary fiber, which helps nourish the gut microbiota,” study coauthor Hannah Holscher, PhD, RD, associate professor of nutrition at the University of Illinois at Urbana-Champaign, told GI & Hepatology News.
Holscher and her colleagues previously conducted a study on the effects of walnut consumption on the human intestinal microbiota “and found interesting results,” she said. Among 18 healthy men and women with a mean age of 53 years, “walnuts enriched intestinal microorganisms, including Roseburia that provide important gut-health promoting attributes, like short-chain fatty acid production. We also saw lower proinflammatory secondary bile acid concentrations in individuals that ate walnuts.”
The current study, presented at NUTRITION 2025 in Orlando, Florida, found similar benefits among 30 adults with obesity but without diabetes or gastrointestinal disease.
Walnut Halves, Walnut Oil, Corn Oil — Compared
The researchers aimed to determine the impact of walnut consumption on the gut microbiome, serum and fecal bile acid profiles, systemic inflammation, and oral glucose tolerance to a mixed-meal challenge.
Participants were enrolled in a randomized, controlled, crossover, complete feeding trial with three 3-week conditions, each identical except for walnut halves (WH), walnut oil (WO), or corn oil (CO) in the diet. A 3-week washout separated each condition.
“This was a fully controlled dietary feeding intervention,” Holscher said. “We provided their breakfast, lunch, snacks and dinners — all of their foods and beverages during the three dietary intervention periods that lasted for 3 weeks each. Their base diet consisted of typical American foods that you would find in a grocery store in central Illinois.”
Fecal samples were collected on days 18-20. On day 20, participants underwent a 6-hour mixed-meal tolerance test (75 g glucose + treatment) with a fasting blood draw followed by blood sampling every 30 minutes.
The fecal microbiome and microbiota were assessed using metagenomic and amplicon sequencing, respectively. Fecal microbial metabolites were quantified using gas chromatography-mass spectrometry.
Blood glucose, insulin, and inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha, C-reactive protein, and lipopolysaccharide-binding protein) were quantified. Fecal and circulating bile acids were measured via liquid chromatography tandem mass spectrometry.
Gut permeability was assessed by quantifying 24-hour urinary excretion of orally ingested sucralose and erythritol on day 21.
Linear mixed-effects models and repeated measures ANOVA were used for the statistical analysis.
The team found that Roseburia spp were greatest following WH (3.9%) vs WO (1.6) and CO (1.9); Lachnospiraceae UCG-001 and UCG-004 were also greatest with WH vs WO and CO.
WH fecal isobutyrate concentrations (5.41 µmol/g) were lower than WO (7.17 µmol/g) and CO (7.77). Similarly, fecal isovalerate concentrations were lowest with WH (7.84 µmol/g) vs WO (10.3µmol/g) and CO (11.6 µmol/g).
In contrast, indoles were highest in WH (36.8 µmol/g) vs WO (6.78 µmol/g) and CO (8.67µmol/g).
No differences in glucose concentrations were seen among groups. The 2-hour area under the curve (AUC) for insulin was lower with WH (469 µIU/mL/min) and WO (494) vs CO (604 µIU/mL/min).
The 4-hour AUC for glycolithocholic acid was lower with WH vs WO and CO. Furthermore, sucralose recovery was lowest following WH (10.5) vs WO (14.3) and CO (14.6).
“Our current efforts are focused on understanding connections between plasma bile acids and glycemic control (ie, blood glucose and insulin concentrations),” Holscher said. “We are also interested in studying individualized or personalized responses, since people had different magnitudes of responses.”
In addition, she said, “as the gut microbiome is one of the factors that can underpin the physiological response to the diet, we are interested in determining if there are microbial signatures that are predictive of glycemic control.”
Because the research is still in the early stages, at this point, Holscher simply encourages people to eat a variety of fruits, vegetables, whole grains, legumes and nuts to meet their daily fiber recommendations and support their gut microbiome.
This study was funded by a USDA NIFA grant. No competing interests were reported.
A version of this article appeared on Medscape.com .
, a small study showed.
“Less than 10% of adults are meeting their fiber needs each day, and walnuts are a source of dietary fiber, which helps nourish the gut microbiota,” study coauthor Hannah Holscher, PhD, RD, associate professor of nutrition at the University of Illinois at Urbana-Champaign, told GI & Hepatology News.
Holscher and her colleagues previously conducted a study on the effects of walnut consumption on the human intestinal microbiota “and found interesting results,” she said. Among 18 healthy men and women with a mean age of 53 years, “walnuts enriched intestinal microorganisms, including Roseburia that provide important gut-health promoting attributes, like short-chain fatty acid production. We also saw lower proinflammatory secondary bile acid concentrations in individuals that ate walnuts.”
The current study, presented at NUTRITION 2025 in Orlando, Florida, found similar benefits among 30 adults with obesity but without diabetes or gastrointestinal disease.
Walnut Halves, Walnut Oil, Corn Oil — Compared
The researchers aimed to determine the impact of walnut consumption on the gut microbiome, serum and fecal bile acid profiles, systemic inflammation, and oral glucose tolerance to a mixed-meal challenge.
Participants were enrolled in a randomized, controlled, crossover, complete feeding trial with three 3-week conditions, each identical except for walnut halves (WH), walnut oil (WO), or corn oil (CO) in the diet. A 3-week washout separated each condition.
“This was a fully controlled dietary feeding intervention,” Holscher said. “We provided their breakfast, lunch, snacks and dinners — all of their foods and beverages during the three dietary intervention periods that lasted for 3 weeks each. Their base diet consisted of typical American foods that you would find in a grocery store in central Illinois.”
Fecal samples were collected on days 18-20. On day 20, participants underwent a 6-hour mixed-meal tolerance test (75 g glucose + treatment) with a fasting blood draw followed by blood sampling every 30 minutes.
The fecal microbiome and microbiota were assessed using metagenomic and amplicon sequencing, respectively. Fecal microbial metabolites were quantified using gas chromatography-mass spectrometry.
Blood glucose, insulin, and inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha, C-reactive protein, and lipopolysaccharide-binding protein) were quantified. Fecal and circulating bile acids were measured via liquid chromatography tandem mass spectrometry.
Gut permeability was assessed by quantifying 24-hour urinary excretion of orally ingested sucralose and erythritol on day 21.
Linear mixed-effects models and repeated measures ANOVA were used for the statistical analysis.
The team found that Roseburia spp were greatest following WH (3.9%) vs WO (1.6) and CO (1.9); Lachnospiraceae UCG-001 and UCG-004 were also greatest with WH vs WO and CO.
WH fecal isobutyrate concentrations (5.41 µmol/g) were lower than WO (7.17 µmol/g) and CO (7.77). Similarly, fecal isovalerate concentrations were lowest with WH (7.84 µmol/g) vs WO (10.3µmol/g) and CO (11.6 µmol/g).
In contrast, indoles were highest in WH (36.8 µmol/g) vs WO (6.78 µmol/g) and CO (8.67µmol/g).
No differences in glucose concentrations were seen among groups. The 2-hour area under the curve (AUC) for insulin was lower with WH (469 µIU/mL/min) and WO (494) vs CO (604 µIU/mL/min).
The 4-hour AUC for glycolithocholic acid was lower with WH vs WO and CO. Furthermore, sucralose recovery was lowest following WH (10.5) vs WO (14.3) and CO (14.6).
“Our current efforts are focused on understanding connections between plasma bile acids and glycemic control (ie, blood glucose and insulin concentrations),” Holscher said. “We are also interested in studying individualized or personalized responses, since people had different magnitudes of responses.”
In addition, she said, “as the gut microbiome is one of the factors that can underpin the physiological response to the diet, we are interested in determining if there are microbial signatures that are predictive of glycemic control.”
Because the research is still in the early stages, at this point, Holscher simply encourages people to eat a variety of fruits, vegetables, whole grains, legumes and nuts to meet their daily fiber recommendations and support their gut microbiome.
This study was funded by a USDA NIFA grant. No competing interests were reported.
A version of this article appeared on Medscape.com .
Intestinal Ultrasound Shows Promise in Prognosis of Early Crohn’s Disease
, a prospective, population-based cohort of newly diagnosed patients in Denmark reported.
Adding to the growing body of evidence on the utility of this noninvasive imaging tool in monitoring disease activity in the newly diagnosed, the multicenter study published in Clinical Gastroenterology and Hepatology characterized ultrasonographic features at diagnosis and evaluated IUS’s prognostic value. Existing literature has focused on patients with long-standing disease.
Investigators led by first author Gorm R. Madsen, MD, PhD, of the Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults at Copenhagen University Hospital, observed continued improvement in most IUS parameters throughout the first year. “Our findings thereby emphasize the role of IUS in improving patient management, and its use in patient risk stratification already at diagnosis,” the investigators wrote.
Some 38% of patients reached ultrasonic transmural remission within 3 months of diagnosis, an achievement associated with higher rates of sustained steroid-free clinical remission and reduced need for treatment escalation.
“Ultrasonic transmural remission is achievable early in Crohn’s disease and is associated with favorable outcomes, underscoring the value of intestinal ultrasound in early disease management,” the researchers wrote.
Study Details
While IUS is increasingly recognized for monitoring CD, little was known about its prognostic value early in the disease course. “We aimed to determine whether sonographic inflammation at diagnosis — and particularly the achievement pftransmural remission after 3 months — could predict future outcomes,” Madsen told GI & Hepatology News. “This is important, as early identification of patients at risk of surgery or treatment escalation may help guide therapy decisions more effectively.”
From May 2021 to April 2023, 201 patients (mean age, 35 years; 54.2% men) with new adult-onset CD were followed by IUS and monitored with symptomatic, biochemical, and endoscopic evaluations.
After 3 months, transmural remission was achieved more often by patients with colonic disease, and no associations were found between sonographic inflammation at diagnosis and diagnostic delay.
“We were positively surprised. Nearly 40% of newly diagnosed Crohn’s patients achieved transmural remission within 3 months — a higher proportion than seen in earlier studies, which mostly focused on long-standing or trial-selected populations,” Madsen said. “It was also striking how strongly early IUS findings predicted the need for surgery, outperforming endoscopy and biomarkers.”
In other findings, transmural remission at 3 months was significantly associated with steroid-free clinical remission at both 3 months and all subsequent follow-ups within the first year. It was also linked to a lower risk for treatment escalation during the follow-up through to 12 months: 26% vs 53% (P =.003). At 12 months, 41% had achieved transmural remission.
Higher baseline body mass index significantly reduced the likelihood of 12-month transmural remission. For overweight, the odds ratio (OR) was 0.34 (95% CI, 0.12-0.94), while for obesity, the OR was 0.16 (95% CI, 0.04-0.73).
The International Bowel Ultrasound Segmental Activity Score in the terminal ileum at diagnosis emerged as the best predictor of ileocecal resection during the first year, with an optimal threshold of 63 (area under the curve, 0.92; sensitivity, 100%; specificity, 73%).
The use of IUS has expanded considerably in the past 3 years, and in 2024, the American Gastroenterological Association updated its clinical practice guidance on the role of this modality in inflammatory bowel disease.
IUS is noninvasive, radiation-free, inexpensive, and doable at the bedside with immediate results, Madsen said. “For patients, this means less anxiety and discomfort. For healthcare systems, it enables faster clinical decisions, reduced need for endoscopy or MRI, and closer disease monitoring, particularly valuable in treat-to-target strategies.”
In terms of limitations, however, IUS is operator-dependent and consistent training is crucial, he added. “Certain anatomical regions, particularly the proximal small bowel, can be more challenging to evaluate. Additionally, while IUS is highly effective for assessing inflammatory activity, it becomes more difficult to accurately assess disease involvement when inflammation extends beyond approximately 20 cm of the small bowel.”
Key Insights
Commenting on the Danish study from a US perspective, Anna L. Silverman, MD, a gastroenterology fellow at Icahn School of Medicine at Mount Sinai in New York City, agreed the findings in adult patients with newly diagnosed, rather than long-standing, CD contribute to the growing body of evidence supporting IUS’s applicability for both treatment monitoring and prognosis.
“By focusing on early-stage CD, the study provides clearer insights into initial disease activity and response to therapy, reinforcing the value of this noninvasive, point-of-care modality,” she told GI & Hepatology News. “These findings enhance our understanding of IUS as a tool to help guide early management decisions in CD.”
Ashwin Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital and an associate professor at Harvard Medical School, both in Boston, concurred that this is an important study. “It includes newly diagnosed patients — so a very ‘clean’ cohort in terms of not being influenced by confounders,” he told GI & Hepatology News.
“We don’t fully know yet the best treatment target in CD, and this study highlights the importance of early transmural healing in determining outcomes at 1 year,” he noted. In addition, the study highlighted a convenient tool that can increasingly be applied at point of care in the United States. “Colonoscopy at 3 months is not practical and has low patient acceptability, so using IUS in this circumstance would have value and impact.”
Ananthakrishnan pointed to several unanswered questions, however. “Are there patients who may not have healing early but may take some extra time to achieve transmural remission, and if so, what are their outcomes? What is the best timepoint for transmural healing assessment? What is the incremental value of measuring it at 3 vs 6 months?”
In addition, he wondered, how much is the added value of IUS over clinical symptoms and/or markers such as calprotectin and C-reactive protein? “In the subset of patients with clinical and transmural remission, there was no difference in endoscopic outcomes at 1 year, so this is an unanswered question,” Ananthakrishnan said.
This study was funded by an unrestricted grant from the Novo Nordisk Foundation.
Madsen reported receiving a speaker’s fee from Tillotts. Multiple coauthors disclosed having various financial relationships with numerous private-sector companies, including Novo Nordisk. Silverman and Ananthakrishnan reported having no competing interests relevant to their comments.
A version of this article appeared on Medscape.com.
, a prospective, population-based cohort of newly diagnosed patients in Denmark reported.
Adding to the growing body of evidence on the utility of this noninvasive imaging tool in monitoring disease activity in the newly diagnosed, the multicenter study published in Clinical Gastroenterology and Hepatology characterized ultrasonographic features at diagnosis and evaluated IUS’s prognostic value. Existing literature has focused on patients with long-standing disease.
Investigators led by first author Gorm R. Madsen, MD, PhD, of the Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults at Copenhagen University Hospital, observed continued improvement in most IUS parameters throughout the first year. “Our findings thereby emphasize the role of IUS in improving patient management, and its use in patient risk stratification already at diagnosis,” the investigators wrote.
Some 38% of patients reached ultrasonic transmural remission within 3 months of diagnosis, an achievement associated with higher rates of sustained steroid-free clinical remission and reduced need for treatment escalation.
“Ultrasonic transmural remission is achievable early in Crohn’s disease and is associated with favorable outcomes, underscoring the value of intestinal ultrasound in early disease management,” the researchers wrote.
Study Details
While IUS is increasingly recognized for monitoring CD, little was known about its prognostic value early in the disease course. “We aimed to determine whether sonographic inflammation at diagnosis — and particularly the achievement pftransmural remission after 3 months — could predict future outcomes,” Madsen told GI & Hepatology News. “This is important, as early identification of patients at risk of surgery or treatment escalation may help guide therapy decisions more effectively.”
From May 2021 to April 2023, 201 patients (mean age, 35 years; 54.2% men) with new adult-onset CD were followed by IUS and monitored with symptomatic, biochemical, and endoscopic evaluations.
After 3 months, transmural remission was achieved more often by patients with colonic disease, and no associations were found between sonographic inflammation at diagnosis and diagnostic delay.
“We were positively surprised. Nearly 40% of newly diagnosed Crohn’s patients achieved transmural remission within 3 months — a higher proportion than seen in earlier studies, which mostly focused on long-standing or trial-selected populations,” Madsen said. “It was also striking how strongly early IUS findings predicted the need for surgery, outperforming endoscopy and biomarkers.”
In other findings, transmural remission at 3 months was significantly associated with steroid-free clinical remission at both 3 months and all subsequent follow-ups within the first year. It was also linked to a lower risk for treatment escalation during the follow-up through to 12 months: 26% vs 53% (P =.003). At 12 months, 41% had achieved transmural remission.
Higher baseline body mass index significantly reduced the likelihood of 12-month transmural remission. For overweight, the odds ratio (OR) was 0.34 (95% CI, 0.12-0.94), while for obesity, the OR was 0.16 (95% CI, 0.04-0.73).
The International Bowel Ultrasound Segmental Activity Score in the terminal ileum at diagnosis emerged as the best predictor of ileocecal resection during the first year, with an optimal threshold of 63 (area under the curve, 0.92; sensitivity, 100%; specificity, 73%).
The use of IUS has expanded considerably in the past 3 years, and in 2024, the American Gastroenterological Association updated its clinical practice guidance on the role of this modality in inflammatory bowel disease.
IUS is noninvasive, radiation-free, inexpensive, and doable at the bedside with immediate results, Madsen said. “For patients, this means less anxiety and discomfort. For healthcare systems, it enables faster clinical decisions, reduced need for endoscopy or MRI, and closer disease monitoring, particularly valuable in treat-to-target strategies.”
In terms of limitations, however, IUS is operator-dependent and consistent training is crucial, he added. “Certain anatomical regions, particularly the proximal small bowel, can be more challenging to evaluate. Additionally, while IUS is highly effective for assessing inflammatory activity, it becomes more difficult to accurately assess disease involvement when inflammation extends beyond approximately 20 cm of the small bowel.”
Key Insights
Commenting on the Danish study from a US perspective, Anna L. Silverman, MD, a gastroenterology fellow at Icahn School of Medicine at Mount Sinai in New York City, agreed the findings in adult patients with newly diagnosed, rather than long-standing, CD contribute to the growing body of evidence supporting IUS’s applicability for both treatment monitoring and prognosis.
“By focusing on early-stage CD, the study provides clearer insights into initial disease activity and response to therapy, reinforcing the value of this noninvasive, point-of-care modality,” she told GI & Hepatology News. “These findings enhance our understanding of IUS as a tool to help guide early management decisions in CD.”
Ashwin Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital and an associate professor at Harvard Medical School, both in Boston, concurred that this is an important study. “It includes newly diagnosed patients — so a very ‘clean’ cohort in terms of not being influenced by confounders,” he told GI & Hepatology News.
“We don’t fully know yet the best treatment target in CD, and this study highlights the importance of early transmural healing in determining outcomes at 1 year,” he noted. In addition, the study highlighted a convenient tool that can increasingly be applied at point of care in the United States. “Colonoscopy at 3 months is not practical and has low patient acceptability, so using IUS in this circumstance would have value and impact.”
Ananthakrishnan pointed to several unanswered questions, however. “Are there patients who may not have healing early but may take some extra time to achieve transmural remission, and if so, what are their outcomes? What is the best timepoint for transmural healing assessment? What is the incremental value of measuring it at 3 vs 6 months?”
In addition, he wondered, how much is the added value of IUS over clinical symptoms and/or markers such as calprotectin and C-reactive protein? “In the subset of patients with clinical and transmural remission, there was no difference in endoscopic outcomes at 1 year, so this is an unanswered question,” Ananthakrishnan said.
This study was funded by an unrestricted grant from the Novo Nordisk Foundation.
Madsen reported receiving a speaker’s fee from Tillotts. Multiple coauthors disclosed having various financial relationships with numerous private-sector companies, including Novo Nordisk. Silverman and Ananthakrishnan reported having no competing interests relevant to their comments.
A version of this article appeared on Medscape.com.
, a prospective, population-based cohort of newly diagnosed patients in Denmark reported.
Adding to the growing body of evidence on the utility of this noninvasive imaging tool in monitoring disease activity in the newly diagnosed, the multicenter study published in Clinical Gastroenterology and Hepatology characterized ultrasonographic features at diagnosis and evaluated IUS’s prognostic value. Existing literature has focused on patients with long-standing disease.
Investigators led by first author Gorm R. Madsen, MD, PhD, of the Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults at Copenhagen University Hospital, observed continued improvement in most IUS parameters throughout the first year. “Our findings thereby emphasize the role of IUS in improving patient management, and its use in patient risk stratification already at diagnosis,” the investigators wrote.
Some 38% of patients reached ultrasonic transmural remission within 3 months of diagnosis, an achievement associated with higher rates of sustained steroid-free clinical remission and reduced need for treatment escalation.
“Ultrasonic transmural remission is achievable early in Crohn’s disease and is associated with favorable outcomes, underscoring the value of intestinal ultrasound in early disease management,” the researchers wrote.
Study Details
While IUS is increasingly recognized for monitoring CD, little was known about its prognostic value early in the disease course. “We aimed to determine whether sonographic inflammation at diagnosis — and particularly the achievement pftransmural remission after 3 months — could predict future outcomes,” Madsen told GI & Hepatology News. “This is important, as early identification of patients at risk of surgery or treatment escalation may help guide therapy decisions more effectively.”
From May 2021 to April 2023, 201 patients (mean age, 35 years; 54.2% men) with new adult-onset CD were followed by IUS and monitored with symptomatic, biochemical, and endoscopic evaluations.
After 3 months, transmural remission was achieved more often by patients with colonic disease, and no associations were found between sonographic inflammation at diagnosis and diagnostic delay.
“We were positively surprised. Nearly 40% of newly diagnosed Crohn’s patients achieved transmural remission within 3 months — a higher proportion than seen in earlier studies, which mostly focused on long-standing or trial-selected populations,” Madsen said. “It was also striking how strongly early IUS findings predicted the need for surgery, outperforming endoscopy and biomarkers.”
In other findings, transmural remission at 3 months was significantly associated with steroid-free clinical remission at both 3 months and all subsequent follow-ups within the first year. It was also linked to a lower risk for treatment escalation during the follow-up through to 12 months: 26% vs 53% (P =.003). At 12 months, 41% had achieved transmural remission.
Higher baseline body mass index significantly reduced the likelihood of 12-month transmural remission. For overweight, the odds ratio (OR) was 0.34 (95% CI, 0.12-0.94), while for obesity, the OR was 0.16 (95% CI, 0.04-0.73).
The International Bowel Ultrasound Segmental Activity Score in the terminal ileum at diagnosis emerged as the best predictor of ileocecal resection during the first year, with an optimal threshold of 63 (area under the curve, 0.92; sensitivity, 100%; specificity, 73%).
The use of IUS has expanded considerably in the past 3 years, and in 2024, the American Gastroenterological Association updated its clinical practice guidance on the role of this modality in inflammatory bowel disease.
IUS is noninvasive, radiation-free, inexpensive, and doable at the bedside with immediate results, Madsen said. “For patients, this means less anxiety and discomfort. For healthcare systems, it enables faster clinical decisions, reduced need for endoscopy or MRI, and closer disease monitoring, particularly valuable in treat-to-target strategies.”
In terms of limitations, however, IUS is operator-dependent and consistent training is crucial, he added. “Certain anatomical regions, particularly the proximal small bowel, can be more challenging to evaluate. Additionally, while IUS is highly effective for assessing inflammatory activity, it becomes more difficult to accurately assess disease involvement when inflammation extends beyond approximately 20 cm of the small bowel.”
Key Insights
Commenting on the Danish study from a US perspective, Anna L. Silverman, MD, a gastroenterology fellow at Icahn School of Medicine at Mount Sinai in New York City, agreed the findings in adult patients with newly diagnosed, rather than long-standing, CD contribute to the growing body of evidence supporting IUS’s applicability for both treatment monitoring and prognosis.
“By focusing on early-stage CD, the study provides clearer insights into initial disease activity and response to therapy, reinforcing the value of this noninvasive, point-of-care modality,” she told GI & Hepatology News. “These findings enhance our understanding of IUS as a tool to help guide early management decisions in CD.”
Ashwin Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital and an associate professor at Harvard Medical School, both in Boston, concurred that this is an important study. “It includes newly diagnosed patients — so a very ‘clean’ cohort in terms of not being influenced by confounders,” he told GI & Hepatology News.
“We don’t fully know yet the best treatment target in CD, and this study highlights the importance of early transmural healing in determining outcomes at 1 year,” he noted. In addition, the study highlighted a convenient tool that can increasingly be applied at point of care in the United States. “Colonoscopy at 3 months is not practical and has low patient acceptability, so using IUS in this circumstance would have value and impact.”
Ananthakrishnan pointed to several unanswered questions, however. “Are there patients who may not have healing early but may take some extra time to achieve transmural remission, and if so, what are their outcomes? What is the best timepoint for transmural healing assessment? What is the incremental value of measuring it at 3 vs 6 months?”
In addition, he wondered, how much is the added value of IUS over clinical symptoms and/or markers such as calprotectin and C-reactive protein? “In the subset of patients with clinical and transmural remission, there was no difference in endoscopic outcomes at 1 year, so this is an unanswered question,” Ananthakrishnan said.
This study was funded by an unrestricted grant from the Novo Nordisk Foundation.
Madsen reported receiving a speaker’s fee from Tillotts. Multiple coauthors disclosed having various financial relationships with numerous private-sector companies, including Novo Nordisk. Silverman and Ananthakrishnan reported having no competing interests relevant to their comments.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AI Algorithm Predicts Transfusion Need, Mortality Risk in Acute GI Bleeds
SAN DIEGO — , researchers reported at Digestive Disease Week® (DDW) 2025.
Acute GI bleeding is the most common cause of digestive disease–related hospitalization, with an estimated 500,000 hospital admissions annually. It’s known that predicting the need for red blood cell transfusion in the first 24 hours may improve resuscitation and decrease both morbidity and mortality.
However, an existing clinical score known as the Rockall Score does not perform well for predicting mortality, Xi (Nicole) Zhang, an MD-PhD student at McGill University, Montreal, Quebec, Canada, told attendees at DDW. With an area under the curve of 0.65-0.75, better prediction is needed, said Zhang, whose coresearchers included Dennis Shung, MD, MHS, PhD, director of Applied Artificial Intelligence at Yale University School of Medicine, New Haven, Connecticut.
“We’d like to predict multiple outcomes in addition to mortality,” said Zhang, who is also a student at the Mila-Quebec Artificial Intelligence Institute.
As a result, the researchers turned to the TFM approach, applying it to ICU patients with acute GI bleeding to predict both the need for transfusion and in-hospital mortality risk. The all-cause mortality rate is up to 11%, according to a 2020 study by James Y. W. Lau, MD, and colleagues. The rebleeding rate of nonvariceal upper GI bleeds is up to 10.4%. Zhang said the rebleeding rate for variceal upper gastrointestinal bleeding is up to 65%.
The AI method the researchers used outperformed a standard deep learning model at predicting the need for transfusion and estimating mortality risk.
Defining the AI Framework
“Probabilistic flow matching is a class of generative artificial intelligence that learns how a simple distribution becomes a more complex distribution with ordinary differential equations,” Zhang told GI & Hepatology News. “For example, if you had a few lines and shapes you could learn how it could become a detailed portrait of a face. In our case, we start with a few blood pressure and heart rate measurements and learn the pattern of blood pressures and heart rates over time, particularly if they reflect clinical deterioration with hemodynamic instability.”
Another way to think about the underlying algorithm, Zhang said, is to think about a river with boats where the river flow determines where the boats end up. “We are trying to direct the boat to the correct dock by adjusting the flow of water in the canal. In this case we are mapping the distribution with the first few data points to the distribution with the entire patient trajectory.”
The information gained, she said, could be helpful in timing endoscopic evaluation or allocating red blood cell products for emergent transfusion.
Study Details
The researchers evaluated a cohort of 2602 patients admitted to the ICU, identified from the publicly available MIMIC-III database. They divided the patients into a training set of 2342 patients and an internal validation set of 260 patients. Input variables were severe liver disease comorbidity, administration of vasopressor medications, mean arterial blood pressure, and heart rate over the first 24 hours.
Excluded was hemoglobin, since the point was to test the trajectory of hemodynamic parameters independent of hemoglobin thresholds used to guide red blood cell transfusion.
The outcome measures were administration of packed red blood cell transfusion within 24 hours and all-cause hospital mortality.
The TFM was more accurate than a standard deep learning model in predicting red blood cell transfusion, with an accuracy of 93.6% vs 43.2%; P ≤ .001. It was also more accurate at predicting all-cause in-hospital mortality, with an accuracy of 89.5% vs 42.5%, P = .01.
The researchers concluded that the TFM approach was able to predict the hemodynamic trajectories of patients with acute GI bleeding defined as deviation and outperformed the baseline from the measured mean arterial pressure and heart rate.
Expert Perspective
“This is an exciting proof-of-concept study that shows generative AI methods may be applied to complex datasets in order to improve on our current predictive models and improve patient care,” said Jeremy Glissen Brown, MD, MSc, an assistant professor of medicine and a practicing gastroenterologist at Duke University who has published research on the use of AI in clinical practice. He reviewed the study for GI & Hepatology News but was not involved in the research.
“Future work will likely look into the implementation of a version of this model on real-time data.” he said. “We are at an exciting inflection point in predictive models within GI and clinical medicine. Predictive models based on deep learning and generative AI hold the promise of improving how we predict and treat disease states, but the excitement being generated with studies such as this needs to be balanced with the trade-offs inherent to the current paradigm of deep learning and generative models compared to more traditional regression-based models. These include many of the same ‘black box’ explainability questions that have risen in the age of convolutional neural networks as well as some method-specific questions due to the continuous and implicit nature of TFM.”
Elaborating on that, Glissen Brown said: “TFM, like many deep learning techniques, raises concerns about explainability that we’ve long seen with convolutional neural networks — the ‘black box’ problem, where it’s difficult to interpret exactly how and why the model arrives at a particular decision. But TFM also introduces unique challenges due to its continuous and implicit formulation. Since it often learns flows without explicitly defining intermediate representations or steps, it can be harder to trace the logic or pathways it uses to connect inputs to outputs. This makes standard interpretability tools less effective and calls for new techniques tailored to these continuous architectures.”
“This approach could have a real clinical impact,” said Robert Hirten, MD, associate professor of medicine and artificial intelligence, Icahn School of Medicine at Mount Sinai, New York City, who also reviewed the study. “Accurately predicting transfusion needs and mortality risk in real time could support earlier, more targeted interventions for high-risk patients. While these findings still need to be validated in prospective studies, it could enhance ICU decision-making and resource allocation.”
“For the practicing gastroenterologist, we envision this system could help them figure out when to perform endoscopy in a patient admitted with acute gastrointestinal bleeding in the ICU at very high risk of exsanguination,” Zhang told GI & Hepatology News.
The approach, the researchers said, will be useful in identifying unique patient characteristics, make possible the identification of high-risk patients and lead to more personalized medicine.
Hirten, Zhang, and Shung had no disclosures. Glissen Brown reported consulting relationships with Medtronic, OdinVision, Doximity, and Olympus. The National Institutes of Health funded this study.
A version of this article appeared on Medscape.com.
SAN DIEGO — , researchers reported at Digestive Disease Week® (DDW) 2025.
Acute GI bleeding is the most common cause of digestive disease–related hospitalization, with an estimated 500,000 hospital admissions annually. It’s known that predicting the need for red blood cell transfusion in the first 24 hours may improve resuscitation and decrease both morbidity and mortality.
However, an existing clinical score known as the Rockall Score does not perform well for predicting mortality, Xi (Nicole) Zhang, an MD-PhD student at McGill University, Montreal, Quebec, Canada, told attendees at DDW. With an area under the curve of 0.65-0.75, better prediction is needed, said Zhang, whose coresearchers included Dennis Shung, MD, MHS, PhD, director of Applied Artificial Intelligence at Yale University School of Medicine, New Haven, Connecticut.
“We’d like to predict multiple outcomes in addition to mortality,” said Zhang, who is also a student at the Mila-Quebec Artificial Intelligence Institute.
As a result, the researchers turned to the TFM approach, applying it to ICU patients with acute GI bleeding to predict both the need for transfusion and in-hospital mortality risk. The all-cause mortality rate is up to 11%, according to a 2020 study by James Y. W. Lau, MD, and colleagues. The rebleeding rate of nonvariceal upper GI bleeds is up to 10.4%. Zhang said the rebleeding rate for variceal upper gastrointestinal bleeding is up to 65%.
The AI method the researchers used outperformed a standard deep learning model at predicting the need for transfusion and estimating mortality risk.
Defining the AI Framework
“Probabilistic flow matching is a class of generative artificial intelligence that learns how a simple distribution becomes a more complex distribution with ordinary differential equations,” Zhang told GI & Hepatology News. “For example, if you had a few lines and shapes you could learn how it could become a detailed portrait of a face. In our case, we start with a few blood pressure and heart rate measurements and learn the pattern of blood pressures and heart rates over time, particularly if they reflect clinical deterioration with hemodynamic instability.”
Another way to think about the underlying algorithm, Zhang said, is to think about a river with boats where the river flow determines where the boats end up. “We are trying to direct the boat to the correct dock by adjusting the flow of water in the canal. In this case we are mapping the distribution with the first few data points to the distribution with the entire patient trajectory.”
The information gained, she said, could be helpful in timing endoscopic evaluation or allocating red blood cell products for emergent transfusion.
Study Details
The researchers evaluated a cohort of 2602 patients admitted to the ICU, identified from the publicly available MIMIC-III database. They divided the patients into a training set of 2342 patients and an internal validation set of 260 patients. Input variables were severe liver disease comorbidity, administration of vasopressor medications, mean arterial blood pressure, and heart rate over the first 24 hours.
Excluded was hemoglobin, since the point was to test the trajectory of hemodynamic parameters independent of hemoglobin thresholds used to guide red blood cell transfusion.
The outcome measures were administration of packed red blood cell transfusion within 24 hours and all-cause hospital mortality.
The TFM was more accurate than a standard deep learning model in predicting red blood cell transfusion, with an accuracy of 93.6% vs 43.2%; P ≤ .001. It was also more accurate at predicting all-cause in-hospital mortality, with an accuracy of 89.5% vs 42.5%, P = .01.
The researchers concluded that the TFM approach was able to predict the hemodynamic trajectories of patients with acute GI bleeding defined as deviation and outperformed the baseline from the measured mean arterial pressure and heart rate.
Expert Perspective
“This is an exciting proof-of-concept study that shows generative AI methods may be applied to complex datasets in order to improve on our current predictive models and improve patient care,” said Jeremy Glissen Brown, MD, MSc, an assistant professor of medicine and a practicing gastroenterologist at Duke University who has published research on the use of AI in clinical practice. He reviewed the study for GI & Hepatology News but was not involved in the research.
“Future work will likely look into the implementation of a version of this model on real-time data.” he said. “We are at an exciting inflection point in predictive models within GI and clinical medicine. Predictive models based on deep learning and generative AI hold the promise of improving how we predict and treat disease states, but the excitement being generated with studies such as this needs to be balanced with the trade-offs inherent to the current paradigm of deep learning and generative models compared to more traditional regression-based models. These include many of the same ‘black box’ explainability questions that have risen in the age of convolutional neural networks as well as some method-specific questions due to the continuous and implicit nature of TFM.”
Elaborating on that, Glissen Brown said: “TFM, like many deep learning techniques, raises concerns about explainability that we’ve long seen with convolutional neural networks — the ‘black box’ problem, where it’s difficult to interpret exactly how and why the model arrives at a particular decision. But TFM also introduces unique challenges due to its continuous and implicit formulation. Since it often learns flows without explicitly defining intermediate representations or steps, it can be harder to trace the logic or pathways it uses to connect inputs to outputs. This makes standard interpretability tools less effective and calls for new techniques tailored to these continuous architectures.”
“This approach could have a real clinical impact,” said Robert Hirten, MD, associate professor of medicine and artificial intelligence, Icahn School of Medicine at Mount Sinai, New York City, who also reviewed the study. “Accurately predicting transfusion needs and mortality risk in real time could support earlier, more targeted interventions for high-risk patients. While these findings still need to be validated in prospective studies, it could enhance ICU decision-making and resource allocation.”
“For the practicing gastroenterologist, we envision this system could help them figure out when to perform endoscopy in a patient admitted with acute gastrointestinal bleeding in the ICU at very high risk of exsanguination,” Zhang told GI & Hepatology News.
The approach, the researchers said, will be useful in identifying unique patient characteristics, make possible the identification of high-risk patients and lead to more personalized medicine.
Hirten, Zhang, and Shung had no disclosures. Glissen Brown reported consulting relationships with Medtronic, OdinVision, Doximity, and Olympus. The National Institutes of Health funded this study.
A version of this article appeared on Medscape.com.
SAN DIEGO — , researchers reported at Digestive Disease Week® (DDW) 2025.
Acute GI bleeding is the most common cause of digestive disease–related hospitalization, with an estimated 500,000 hospital admissions annually. It’s known that predicting the need for red blood cell transfusion in the first 24 hours may improve resuscitation and decrease both morbidity and mortality.
However, an existing clinical score known as the Rockall Score does not perform well for predicting mortality, Xi (Nicole) Zhang, an MD-PhD student at McGill University, Montreal, Quebec, Canada, told attendees at DDW. With an area under the curve of 0.65-0.75, better prediction is needed, said Zhang, whose coresearchers included Dennis Shung, MD, MHS, PhD, director of Applied Artificial Intelligence at Yale University School of Medicine, New Haven, Connecticut.
“We’d like to predict multiple outcomes in addition to mortality,” said Zhang, who is also a student at the Mila-Quebec Artificial Intelligence Institute.
As a result, the researchers turned to the TFM approach, applying it to ICU patients with acute GI bleeding to predict both the need for transfusion and in-hospital mortality risk. The all-cause mortality rate is up to 11%, according to a 2020 study by James Y. W. Lau, MD, and colleagues. The rebleeding rate of nonvariceal upper GI bleeds is up to 10.4%. Zhang said the rebleeding rate for variceal upper gastrointestinal bleeding is up to 65%.
The AI method the researchers used outperformed a standard deep learning model at predicting the need for transfusion and estimating mortality risk.
Defining the AI Framework
“Probabilistic flow matching is a class of generative artificial intelligence that learns how a simple distribution becomes a more complex distribution with ordinary differential equations,” Zhang told GI & Hepatology News. “For example, if you had a few lines and shapes you could learn how it could become a detailed portrait of a face. In our case, we start with a few blood pressure and heart rate measurements and learn the pattern of blood pressures and heart rates over time, particularly if they reflect clinical deterioration with hemodynamic instability.”
Another way to think about the underlying algorithm, Zhang said, is to think about a river with boats where the river flow determines where the boats end up. “We are trying to direct the boat to the correct dock by adjusting the flow of water in the canal. In this case we are mapping the distribution with the first few data points to the distribution with the entire patient trajectory.”
The information gained, she said, could be helpful in timing endoscopic evaluation or allocating red blood cell products for emergent transfusion.
Study Details
The researchers evaluated a cohort of 2602 patients admitted to the ICU, identified from the publicly available MIMIC-III database. They divided the patients into a training set of 2342 patients and an internal validation set of 260 patients. Input variables were severe liver disease comorbidity, administration of vasopressor medications, mean arterial blood pressure, and heart rate over the first 24 hours.
Excluded was hemoglobin, since the point was to test the trajectory of hemodynamic parameters independent of hemoglobin thresholds used to guide red blood cell transfusion.
The outcome measures were administration of packed red blood cell transfusion within 24 hours and all-cause hospital mortality.
The TFM was more accurate than a standard deep learning model in predicting red blood cell transfusion, with an accuracy of 93.6% vs 43.2%; P ≤ .001. It was also more accurate at predicting all-cause in-hospital mortality, with an accuracy of 89.5% vs 42.5%, P = .01.
The researchers concluded that the TFM approach was able to predict the hemodynamic trajectories of patients with acute GI bleeding defined as deviation and outperformed the baseline from the measured mean arterial pressure and heart rate.
Expert Perspective
“This is an exciting proof-of-concept study that shows generative AI methods may be applied to complex datasets in order to improve on our current predictive models and improve patient care,” said Jeremy Glissen Brown, MD, MSc, an assistant professor of medicine and a practicing gastroenterologist at Duke University who has published research on the use of AI in clinical practice. He reviewed the study for GI & Hepatology News but was not involved in the research.
“Future work will likely look into the implementation of a version of this model on real-time data.” he said. “We are at an exciting inflection point in predictive models within GI and clinical medicine. Predictive models based on deep learning and generative AI hold the promise of improving how we predict and treat disease states, but the excitement being generated with studies such as this needs to be balanced with the trade-offs inherent to the current paradigm of deep learning and generative models compared to more traditional regression-based models. These include many of the same ‘black box’ explainability questions that have risen in the age of convolutional neural networks as well as some method-specific questions due to the continuous and implicit nature of TFM.”
Elaborating on that, Glissen Brown said: “TFM, like many deep learning techniques, raises concerns about explainability that we’ve long seen with convolutional neural networks — the ‘black box’ problem, where it’s difficult to interpret exactly how and why the model arrives at a particular decision. But TFM also introduces unique challenges due to its continuous and implicit formulation. Since it often learns flows without explicitly defining intermediate representations or steps, it can be harder to trace the logic or pathways it uses to connect inputs to outputs. This makes standard interpretability tools less effective and calls for new techniques tailored to these continuous architectures.”
“This approach could have a real clinical impact,” said Robert Hirten, MD, associate professor of medicine and artificial intelligence, Icahn School of Medicine at Mount Sinai, New York City, who also reviewed the study. “Accurately predicting transfusion needs and mortality risk in real time could support earlier, more targeted interventions for high-risk patients. While these findings still need to be validated in prospective studies, it could enhance ICU decision-making and resource allocation.”
“For the practicing gastroenterologist, we envision this system could help them figure out when to perform endoscopy in a patient admitted with acute gastrointestinal bleeding in the ICU at very high risk of exsanguination,” Zhang told GI & Hepatology News.
The approach, the researchers said, will be useful in identifying unique patient characteristics, make possible the identification of high-risk patients and lead to more personalized medicine.
Hirten, Zhang, and Shung had no disclosures. Glissen Brown reported consulting relationships with Medtronic, OdinVision, Doximity, and Olympus. The National Institutes of Health funded this study.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Ostomy Innovation Grabs ‘Shark Tank’ Win
The “Shark Tank” winning innovation at the American Gastroenterological Association (AGA) Tech Summit in Chicago this April has “life-altering” potential for ostomy patients, according to one of the judges, and eliminates the need for constant pouch wear.
The innovation is called Twistomy and it is designed to replace current ostomy-pouch systems that can cause leaks, odor, skin irritation, embarrassment, and social and emotional distress. The AGA Committee for GI Innovation and Technology (CGIT) organizes the annual Tech Summit.
Twistomy’s winning design includes a flexible ring and sleeve, which are inserted into the stoma and secured on the outside with a set of rings that make up the housing unit attached to a standard wafer. The housing unit twists the sleeve closed, allowing the user to control fecal output. For evacuation, the user attaches a pouch, untwists the sleeve, evacuates cleanly and effectively, and then discards the pouch.
Twistomy cofounders Devon Horton, BS, senior bioengineer, and Lily Williams, BS, biomedical researcher and engineer, both work for the department of surgery at University of Colorado, Denver.
Horton said in an interview that when he was approached with the idea to create a better ostomy solution for a senior-year capstone project he was intrigued because the traditional ostomy system “has not changed in more than 70 years. It was crazy that no one had done anything to change that.”
The Twistomy team also won the Grand Prize this spring at the Emerging Medical Innovation Valuation Competition at the Design of Medical Devices Conference held at the University of Minnesota, Minneapolis.
Witnessing the Struggle as a CNA
Horton also works as a certified nursing assistant at an inpatient unit at University of Colorado Hospital and the ostomy patients he sees there every shift help drive his passion to find a better solution.
He hears the emotional stories of people who manage their ostomy daily.
“Many express feelings of depression and anxiety, feeling isolated with their severe inability to go out and do things because of the fear of the noise the stoma makes, or the crinkling of the plastic bag in a yoga class,” he said. “We want to help them regain that control of quality of life.”
They also hope to cut down on the ostomy management time. “Initial user testing [for Twistomy] was less than 75 seconds to insert and assemble,” he said. “I did an interview with a patient yesterday who said they probably spend an hour a day managing their ostomy,” including cleaning and replacing.
Horton and Williams have a patent on the device and currently use three-dimensional printing for the prototypes.
Williams said they are now conducting consumer discovery studies through the National Science Foundation and are interviewing 30 stakeholders — “anyone who has a relationship with an ostomy,” whether a colorectal surgeon, a gastrointestinal nurse, ostomy patients, or insurers.
Those interviews will help in refining the device so they can start consulting with manufacturers and work toward approval as a Class II medical device from the US Food and Drug Administration (FDA), Williams said.
Saving Healthcare Costs
Another potential benefit for Twistomy is its ability to cut healthcare costs, Horton said. Traditional ostomies are prone to leakage, which can lead to peristomal skin complications.
He pointed to a National Institutes of Health analysis that found that on average peristomal skin complications caused upwards of $80,000 more per ostomy patient in increased healthcare costs over a 3-month period than for those without the complications.
“With Twistomy, we are reducing leakage most likely to zero,” Horton said. “We set out to say if we could reduce [infections] by half or a little less than half, we can cut out those tens of thousands of dollars that insurance companies and payers are spending.”
Permanent and Temporary Ostomy Markets
He pointed out that not all ostomies are permanent ostomies, adding that the reversal rate “is about 65%.” Often those reversal surgeries cannot take place until peristomal skin complications have been healed.
“We’re not only hoping to market to the permanent stoma patients, but the patients with temporary stomas as well,” he said.
The team estimates it will need $4 million–$6 million in funding for manufacturing and consultation costs as well as costs involved in seeking FDA approval.
Horton and Williams project the housing unit cost will be $399 based on known out-of-pocket expenses for patients with ostomy care products and the unit would be replaced annually. Disposable elements would be an additional cost.
Assuming insurance acceptance of the product, he said, “With about an 80/20 insurance coverage, typical for many patients, it would be about $100 in out-of-pocket expenses per month to use our device, which is around the lower end of what a lot of patients are spending out of pocket.”
One of the Tech Summit judges, Somaya Albhaisi, MD, a gastroenterology/hepatology fellow at University of Southern California, Los Angeles, said in an interview that the Shark Tank results were unanimous among the five judges and Twistomy also took the fan favorite vote.
She said the teams were judged on quality of pitch, potential clinical impact, and feasibility of business plan. Teams got 5-7 minutes to pitch and answered questions afterward.
“Deep Understanding” of Patient Need
“They combined smart engineering with deep understanding of patient need, which is restoring control, dignity, and quality of life for ostomy users while also reducing healthcare costs. It is rare to see a solution this scalable and impactful. It was a deeply empathetic solution overall.” She noted that nearly 1 million people in the United States currently use an ostomy.
Ostomy users’ quality of life is compromised, and they often have mental health challenges, Albhaisi said. This innovation appears to offer easy use, more dignity and control.
The other four Shark Tank finalists were:
- AI Lumen, which developed a retroview camera system, which attaches to the colonoscope and enhances imaging to detect hidden polyps that may evade conventional endoscopes.
- Amplified Sciences, which developed an ultrasensitive diagnostic platform that detects biomarker activities in minute volumes of fluid from pancreatic cystic lesions, helping to stratify patients into low risk or potential malignancy, reducing unneeded surgeries, costs, and comorbidities.
- KITE Endoscopic Innovations, which designed the Dynaflex TruCut needle to offer a simpler endoscopic ultrasound (EUS)–guided biopsy procedure with fewer needle passes, deeper insights into tumor pathology, and more tissue for geonomic analysis.
- MicroSteer, which designed a device to facilitate semiautomated endoscopic submucosal dissection (ESD) by decoupling the dissecting knife from the endoscope, enhancing safety and effectiveness during the procedure.
The Twistomy Team “Surprised Everyone”
The competitors’ scores were “very close,” one of the judges, Kevin Berliner, said in an interview. “The Twistomy team surprised everyone — the judges and the crowd — with their succinct, informative, and impactful pitch. That presentation disparity was the tiebreaker for me,” said Berliner, who works for Medtronic, a sponsor of the competition, in Chicago.
He said Horton and Williams were the youngest presenters and had the earliest stage pitch they judged, but they “outpresented other competitors in clarity, simplification, and storytelling.”
Also impressive was their description of their “commercially viable path to success” and their plan for the challenges ahead, he said.
Those challenges to get Twistomy to market center “on the ongoing changing climate we have with research funds lately,” Horton said. “We’re giving it an estimate of 3-5 years.”
Horton, Williams, Albhaisi, and Berliner reported no relevant financial relationships.
The “Shark Tank” winning innovation at the American Gastroenterological Association (AGA) Tech Summit in Chicago this April has “life-altering” potential for ostomy patients, according to one of the judges, and eliminates the need for constant pouch wear.
The innovation is called Twistomy and it is designed to replace current ostomy-pouch systems that can cause leaks, odor, skin irritation, embarrassment, and social and emotional distress. The AGA Committee for GI Innovation and Technology (CGIT) organizes the annual Tech Summit.
Twistomy’s winning design includes a flexible ring and sleeve, which are inserted into the stoma and secured on the outside with a set of rings that make up the housing unit attached to a standard wafer. The housing unit twists the sleeve closed, allowing the user to control fecal output. For evacuation, the user attaches a pouch, untwists the sleeve, evacuates cleanly and effectively, and then discards the pouch.
Twistomy cofounders Devon Horton, BS, senior bioengineer, and Lily Williams, BS, biomedical researcher and engineer, both work for the department of surgery at University of Colorado, Denver.
Horton said in an interview that when he was approached with the idea to create a better ostomy solution for a senior-year capstone project he was intrigued because the traditional ostomy system “has not changed in more than 70 years. It was crazy that no one had done anything to change that.”
The Twistomy team also won the Grand Prize this spring at the Emerging Medical Innovation Valuation Competition at the Design of Medical Devices Conference held at the University of Minnesota, Minneapolis.
Witnessing the Struggle as a CNA
Horton also works as a certified nursing assistant at an inpatient unit at University of Colorado Hospital and the ostomy patients he sees there every shift help drive his passion to find a better solution.
He hears the emotional stories of people who manage their ostomy daily.
“Many express feelings of depression and anxiety, feeling isolated with their severe inability to go out and do things because of the fear of the noise the stoma makes, or the crinkling of the plastic bag in a yoga class,” he said. “We want to help them regain that control of quality of life.”
They also hope to cut down on the ostomy management time. “Initial user testing [for Twistomy] was less than 75 seconds to insert and assemble,” he said. “I did an interview with a patient yesterday who said they probably spend an hour a day managing their ostomy,” including cleaning and replacing.
Horton and Williams have a patent on the device and currently use three-dimensional printing for the prototypes.
Williams said they are now conducting consumer discovery studies through the National Science Foundation and are interviewing 30 stakeholders — “anyone who has a relationship with an ostomy,” whether a colorectal surgeon, a gastrointestinal nurse, ostomy patients, or insurers.
Those interviews will help in refining the device so they can start consulting with manufacturers and work toward approval as a Class II medical device from the US Food and Drug Administration (FDA), Williams said.
Saving Healthcare Costs
Another potential benefit for Twistomy is its ability to cut healthcare costs, Horton said. Traditional ostomies are prone to leakage, which can lead to peristomal skin complications.
He pointed to a National Institutes of Health analysis that found that on average peristomal skin complications caused upwards of $80,000 more per ostomy patient in increased healthcare costs over a 3-month period than for those without the complications.
“With Twistomy, we are reducing leakage most likely to zero,” Horton said. “We set out to say if we could reduce [infections] by half or a little less than half, we can cut out those tens of thousands of dollars that insurance companies and payers are spending.”
Permanent and Temporary Ostomy Markets
He pointed out that not all ostomies are permanent ostomies, adding that the reversal rate “is about 65%.” Often those reversal surgeries cannot take place until peristomal skin complications have been healed.
“We’re not only hoping to market to the permanent stoma patients, but the patients with temporary stomas as well,” he said.
The team estimates it will need $4 million–$6 million in funding for manufacturing and consultation costs as well as costs involved in seeking FDA approval.
Horton and Williams project the housing unit cost will be $399 based on known out-of-pocket expenses for patients with ostomy care products and the unit would be replaced annually. Disposable elements would be an additional cost.
Assuming insurance acceptance of the product, he said, “With about an 80/20 insurance coverage, typical for many patients, it would be about $100 in out-of-pocket expenses per month to use our device, which is around the lower end of what a lot of patients are spending out of pocket.”
One of the Tech Summit judges, Somaya Albhaisi, MD, a gastroenterology/hepatology fellow at University of Southern California, Los Angeles, said in an interview that the Shark Tank results were unanimous among the five judges and Twistomy also took the fan favorite vote.
She said the teams were judged on quality of pitch, potential clinical impact, and feasibility of business plan. Teams got 5-7 minutes to pitch and answered questions afterward.
“Deep Understanding” of Patient Need
“They combined smart engineering with deep understanding of patient need, which is restoring control, dignity, and quality of life for ostomy users while also reducing healthcare costs. It is rare to see a solution this scalable and impactful. It was a deeply empathetic solution overall.” She noted that nearly 1 million people in the United States currently use an ostomy.
Ostomy users’ quality of life is compromised, and they often have mental health challenges, Albhaisi said. This innovation appears to offer easy use, more dignity and control.
The other four Shark Tank finalists were:
- AI Lumen, which developed a retroview camera system, which attaches to the colonoscope and enhances imaging to detect hidden polyps that may evade conventional endoscopes.
- Amplified Sciences, which developed an ultrasensitive diagnostic platform that detects biomarker activities in minute volumes of fluid from pancreatic cystic lesions, helping to stratify patients into low risk or potential malignancy, reducing unneeded surgeries, costs, and comorbidities.
- KITE Endoscopic Innovations, which designed the Dynaflex TruCut needle to offer a simpler endoscopic ultrasound (EUS)–guided biopsy procedure with fewer needle passes, deeper insights into tumor pathology, and more tissue for geonomic analysis.
- MicroSteer, which designed a device to facilitate semiautomated endoscopic submucosal dissection (ESD) by decoupling the dissecting knife from the endoscope, enhancing safety and effectiveness during the procedure.
The Twistomy Team “Surprised Everyone”
The competitors’ scores were “very close,” one of the judges, Kevin Berliner, said in an interview. “The Twistomy team surprised everyone — the judges and the crowd — with their succinct, informative, and impactful pitch. That presentation disparity was the tiebreaker for me,” said Berliner, who works for Medtronic, a sponsor of the competition, in Chicago.
He said Horton and Williams were the youngest presenters and had the earliest stage pitch they judged, but they “outpresented other competitors in clarity, simplification, and storytelling.”
Also impressive was their description of their “commercially viable path to success” and their plan for the challenges ahead, he said.
Those challenges to get Twistomy to market center “on the ongoing changing climate we have with research funds lately,” Horton said. “We’re giving it an estimate of 3-5 years.”
Horton, Williams, Albhaisi, and Berliner reported no relevant financial relationships.
The “Shark Tank” winning innovation at the American Gastroenterological Association (AGA) Tech Summit in Chicago this April has “life-altering” potential for ostomy patients, according to one of the judges, and eliminates the need for constant pouch wear.
The innovation is called Twistomy and it is designed to replace current ostomy-pouch systems that can cause leaks, odor, skin irritation, embarrassment, and social and emotional distress. The AGA Committee for GI Innovation and Technology (CGIT) organizes the annual Tech Summit.
Twistomy’s winning design includes a flexible ring and sleeve, which are inserted into the stoma and secured on the outside with a set of rings that make up the housing unit attached to a standard wafer. The housing unit twists the sleeve closed, allowing the user to control fecal output. For evacuation, the user attaches a pouch, untwists the sleeve, evacuates cleanly and effectively, and then discards the pouch.
Twistomy cofounders Devon Horton, BS, senior bioengineer, and Lily Williams, BS, biomedical researcher and engineer, both work for the department of surgery at University of Colorado, Denver.
Horton said in an interview that when he was approached with the idea to create a better ostomy solution for a senior-year capstone project he was intrigued because the traditional ostomy system “has not changed in more than 70 years. It was crazy that no one had done anything to change that.”
The Twistomy team also won the Grand Prize this spring at the Emerging Medical Innovation Valuation Competition at the Design of Medical Devices Conference held at the University of Minnesota, Minneapolis.
Witnessing the Struggle as a CNA
Horton also works as a certified nursing assistant at an inpatient unit at University of Colorado Hospital and the ostomy patients he sees there every shift help drive his passion to find a better solution.
He hears the emotional stories of people who manage their ostomy daily.
“Many express feelings of depression and anxiety, feeling isolated with their severe inability to go out and do things because of the fear of the noise the stoma makes, or the crinkling of the plastic bag in a yoga class,” he said. “We want to help them regain that control of quality of life.”
They also hope to cut down on the ostomy management time. “Initial user testing [for Twistomy] was less than 75 seconds to insert and assemble,” he said. “I did an interview with a patient yesterday who said they probably spend an hour a day managing their ostomy,” including cleaning and replacing.
Horton and Williams have a patent on the device and currently use three-dimensional printing for the prototypes.
Williams said they are now conducting consumer discovery studies through the National Science Foundation and are interviewing 30 stakeholders — “anyone who has a relationship with an ostomy,” whether a colorectal surgeon, a gastrointestinal nurse, ostomy patients, or insurers.
Those interviews will help in refining the device so they can start consulting with manufacturers and work toward approval as a Class II medical device from the US Food and Drug Administration (FDA), Williams said.
Saving Healthcare Costs
Another potential benefit for Twistomy is its ability to cut healthcare costs, Horton said. Traditional ostomies are prone to leakage, which can lead to peristomal skin complications.
He pointed to a National Institutes of Health analysis that found that on average peristomal skin complications caused upwards of $80,000 more per ostomy patient in increased healthcare costs over a 3-month period than for those without the complications.
“With Twistomy, we are reducing leakage most likely to zero,” Horton said. “We set out to say if we could reduce [infections] by half or a little less than half, we can cut out those tens of thousands of dollars that insurance companies and payers are spending.”
Permanent and Temporary Ostomy Markets
He pointed out that not all ostomies are permanent ostomies, adding that the reversal rate “is about 65%.” Often those reversal surgeries cannot take place until peristomal skin complications have been healed.
“We’re not only hoping to market to the permanent stoma patients, but the patients with temporary stomas as well,” he said.
The team estimates it will need $4 million–$6 million in funding for manufacturing and consultation costs as well as costs involved in seeking FDA approval.
Horton and Williams project the housing unit cost will be $399 based on known out-of-pocket expenses for patients with ostomy care products and the unit would be replaced annually. Disposable elements would be an additional cost.
Assuming insurance acceptance of the product, he said, “With about an 80/20 insurance coverage, typical for many patients, it would be about $100 in out-of-pocket expenses per month to use our device, which is around the lower end of what a lot of patients are spending out of pocket.”
One of the Tech Summit judges, Somaya Albhaisi, MD, a gastroenterology/hepatology fellow at University of Southern California, Los Angeles, said in an interview that the Shark Tank results were unanimous among the five judges and Twistomy also took the fan favorite vote.
She said the teams were judged on quality of pitch, potential clinical impact, and feasibility of business plan. Teams got 5-7 minutes to pitch and answered questions afterward.
“Deep Understanding” of Patient Need
“They combined smart engineering with deep understanding of patient need, which is restoring control, dignity, and quality of life for ostomy users while also reducing healthcare costs. It is rare to see a solution this scalable and impactful. It was a deeply empathetic solution overall.” She noted that nearly 1 million people in the United States currently use an ostomy.
Ostomy users’ quality of life is compromised, and they often have mental health challenges, Albhaisi said. This innovation appears to offer easy use, more dignity and control.
The other four Shark Tank finalists were:
- AI Lumen, which developed a retroview camera system, which attaches to the colonoscope and enhances imaging to detect hidden polyps that may evade conventional endoscopes.
- Amplified Sciences, which developed an ultrasensitive diagnostic platform that detects biomarker activities in minute volumes of fluid from pancreatic cystic lesions, helping to stratify patients into low risk or potential malignancy, reducing unneeded surgeries, costs, and comorbidities.
- KITE Endoscopic Innovations, which designed the Dynaflex TruCut needle to offer a simpler endoscopic ultrasound (EUS)–guided biopsy procedure with fewer needle passes, deeper insights into tumor pathology, and more tissue for geonomic analysis.
- MicroSteer, which designed a device to facilitate semiautomated endoscopic submucosal dissection (ESD) by decoupling the dissecting knife from the endoscope, enhancing safety and effectiveness during the procedure.
The Twistomy Team “Surprised Everyone”
The competitors’ scores were “very close,” one of the judges, Kevin Berliner, said in an interview. “The Twistomy team surprised everyone — the judges and the crowd — with their succinct, informative, and impactful pitch. That presentation disparity was the tiebreaker for me,” said Berliner, who works for Medtronic, a sponsor of the competition, in Chicago.
He said Horton and Williams were the youngest presenters and had the earliest stage pitch they judged, but they “outpresented other competitors in clarity, simplification, and storytelling.”
Also impressive was their description of their “commercially viable path to success” and their plan for the challenges ahead, he said.
Those challenges to get Twistomy to market center “on the ongoing changing climate we have with research funds lately,” Horton said. “We’re giving it an estimate of 3-5 years.”
Horton, Williams, Albhaisi, and Berliner reported no relevant financial relationships.
Chatbot Helps Users Adopt a Low FODMAP Diet
SAN DIEGO — Low fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) dietary advice has been shown to be effective in easing bloating and abdominal pain, especially in patients with irritable bowel syndrome (IBS), but limited availability of dietitians makes delivering this advice challenging. Researchers from Thailand have successfully enlisted a chatbot to help.
In a randomized controlled trial, they found that chatbot-assisted dietary advice with brief guidance effectively reduced high FODMAP intake, bloating severity, and improved dietary knowledge, particularly in patients with bothersome bloating.
“Chatbot-assisted dietary advice for FODMAPs restriction was feasible and applicable in patients with bloating symptoms that had baseline symptoms of moderate severity,” study chief Pochara Somvanapanich, with the Division of Gastroenterology, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand, told GI & Hepatology News.
Somvanapanich, who developed the chatbot algorithm, presented the study results at Digestive Disease Week (DDW) 2025.
More Knowledge, Less Bloating
The trial enrolled 86 adults with disorders of gut-brain interaction experiencing bloating symptoms for more than 6 months and consuming more than seven high-FODMAPs items per week. Half of them had IBS.
At baseline, gastrointestinal (GI) symptoms and the ability to identify FODMAPs were assessed. All participants received a 5-minute consultation on FODMAPs avoidance from a GI fellow and were randomly allocated (stratified by IBS diagnosis and education) into two groups.
The chatbot-assisted group received real-time dietary advice via a chatbot which helped them identify high, low, and non-FODMAP foods from a list of more than 300 ingredients/dishes of Thai and western cuisines.
The control group received only brief advice on high FODMAPs restriction. Both groups used a diary app to log food intake and postprandial symptoms. Baseline bloating, abdominal pain and global symptoms severity were similar between the two groups. Data on 64 participants (32 in each group) were analyzed.
After 4 weeks, significantly more people in the chatbot group than the control group responded — achieving a 30% or greater reduction in daily worst bloating, abdominal pain or global symptoms (19 [59%] vs 10 [31%], P < .05). Responder rates were similar in the IBS and non-IBS subgroups.
Subgroup analysis revealed significant differences between groups only for participants with bothersome bloating, not those with mild bloating severity.
In those with bothersome bloating severity, the chatbot group had a higher response rate (69.5% vs 36.3%) and fewer bloating symptoms (P < .05). They also had a greater reduction in high FODMAPs intake (10 vs 23 items/week) and demonstrated improved knowledge in identifying FODMAPs (P < .05).
“Responders in a chatbot group consistently engaged more with the app, performing significantly more weekly item searches than nonresponders (P < .05),” the authors noted in their conference abstract.
“Our next step is to develop the chatbot-assisted approach for the reintroduction and personalization phase based on messenger applications (including Facebook Messenger and other messaging platforms),” Somvanapanich told GI & Hepatology News.
“Once we’ve gathered enough data to confirm these are working effectively, we definitely plan to create a one-stop service application for FODMAPs dietary advice,” Somvanapanich added.
Lack of Robust Data on Digital GI Health Apps
Commenting on this research for GI & Hepatology News, Sidhartha R. Sinha, MD, Director of Digital Health and Innovation, Division of Gastroenterology and Hepatology, Stanford University in Stanford, California, noted that there is a “notable lack of robust data supporting digital health tools in gastroenterology. Despite hundreds of apps available, very few are supported by well-designed trials.”
“The study demonstrated that chatbot-assisted dietary advice significantly improved bloating symptoms, reduced intake of high-FODMAP foods, and enhanced patients’ dietary knowledge compared to brief dietary counseling alone, especially in those with bothersome symptoms,” said Sinha, who wasn’t involved in the study.
“Patients actively used the chatbot to manage their symptoms, achieving a higher response rate than those in the control arm who received brief counseling on avoiding high-FODMAP food,” he noted.
Sinha said in his practice at Stanford, “in the heart of Silicon Valley,” patients do use digital resources to manage their GI symptoms, including diseases like IBS and inflammatory bowel disease (IBD) — and he believes this is “increasingly common nationally.”
“However, the need for evidence-based tools is critical and the lack here often prevents many practitioners from regularly recommending them to patients. This study aligns well with clinical practice, and supports the use of this particular app to improve IBS symptoms, particularly when access to dietitians is limited. These results support chatbot-assisted dietary management as a feasible, effective, and scalable approach to patient care,” Sinha told GI & Hepatology News.
The study received no commercial funding. Somvanapanich and Sinha had no relevant disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO — Low fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) dietary advice has been shown to be effective in easing bloating and abdominal pain, especially in patients with irritable bowel syndrome (IBS), but limited availability of dietitians makes delivering this advice challenging. Researchers from Thailand have successfully enlisted a chatbot to help.
In a randomized controlled trial, they found that chatbot-assisted dietary advice with brief guidance effectively reduced high FODMAP intake, bloating severity, and improved dietary knowledge, particularly in patients with bothersome bloating.
“Chatbot-assisted dietary advice for FODMAPs restriction was feasible and applicable in patients with bloating symptoms that had baseline symptoms of moderate severity,” study chief Pochara Somvanapanich, with the Division of Gastroenterology, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand, told GI & Hepatology News.
Somvanapanich, who developed the chatbot algorithm, presented the study results at Digestive Disease Week (DDW) 2025.
More Knowledge, Less Bloating
The trial enrolled 86 adults with disorders of gut-brain interaction experiencing bloating symptoms for more than 6 months and consuming more than seven high-FODMAPs items per week. Half of them had IBS.
At baseline, gastrointestinal (GI) symptoms and the ability to identify FODMAPs were assessed. All participants received a 5-minute consultation on FODMAPs avoidance from a GI fellow and were randomly allocated (stratified by IBS diagnosis and education) into two groups.
The chatbot-assisted group received real-time dietary advice via a chatbot which helped them identify high, low, and non-FODMAP foods from a list of more than 300 ingredients/dishes of Thai and western cuisines.
The control group received only brief advice on high FODMAPs restriction. Both groups used a diary app to log food intake and postprandial symptoms. Baseline bloating, abdominal pain and global symptoms severity were similar between the two groups. Data on 64 participants (32 in each group) were analyzed.
After 4 weeks, significantly more people in the chatbot group than the control group responded — achieving a 30% or greater reduction in daily worst bloating, abdominal pain or global symptoms (19 [59%] vs 10 [31%], P < .05). Responder rates were similar in the IBS and non-IBS subgroups.
Subgroup analysis revealed significant differences between groups only for participants with bothersome bloating, not those with mild bloating severity.
In those with bothersome bloating severity, the chatbot group had a higher response rate (69.5% vs 36.3%) and fewer bloating symptoms (P < .05). They also had a greater reduction in high FODMAPs intake (10 vs 23 items/week) and demonstrated improved knowledge in identifying FODMAPs (P < .05).
“Responders in a chatbot group consistently engaged more with the app, performing significantly more weekly item searches than nonresponders (P < .05),” the authors noted in their conference abstract.
“Our next step is to develop the chatbot-assisted approach for the reintroduction and personalization phase based on messenger applications (including Facebook Messenger and other messaging platforms),” Somvanapanich told GI & Hepatology News.
“Once we’ve gathered enough data to confirm these are working effectively, we definitely plan to create a one-stop service application for FODMAPs dietary advice,” Somvanapanich added.
Lack of Robust Data on Digital GI Health Apps
Commenting on this research for GI & Hepatology News, Sidhartha R. Sinha, MD, Director of Digital Health and Innovation, Division of Gastroenterology and Hepatology, Stanford University in Stanford, California, noted that there is a “notable lack of robust data supporting digital health tools in gastroenterology. Despite hundreds of apps available, very few are supported by well-designed trials.”
“The study demonstrated that chatbot-assisted dietary advice significantly improved bloating symptoms, reduced intake of high-FODMAP foods, and enhanced patients’ dietary knowledge compared to brief dietary counseling alone, especially in those with bothersome symptoms,” said Sinha, who wasn’t involved in the study.
“Patients actively used the chatbot to manage their symptoms, achieving a higher response rate than those in the control arm who received brief counseling on avoiding high-FODMAP food,” he noted.
Sinha said in his practice at Stanford, “in the heart of Silicon Valley,” patients do use digital resources to manage their GI symptoms, including diseases like IBS and inflammatory bowel disease (IBD) — and he believes this is “increasingly common nationally.”
“However, the need for evidence-based tools is critical and the lack here often prevents many practitioners from regularly recommending them to patients. This study aligns well with clinical practice, and supports the use of this particular app to improve IBS symptoms, particularly when access to dietitians is limited. These results support chatbot-assisted dietary management as a feasible, effective, and scalable approach to patient care,” Sinha told GI & Hepatology News.
The study received no commercial funding. Somvanapanich and Sinha had no relevant disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO — Low fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) dietary advice has been shown to be effective in easing bloating and abdominal pain, especially in patients with irritable bowel syndrome (IBS), but limited availability of dietitians makes delivering this advice challenging. Researchers from Thailand have successfully enlisted a chatbot to help.
In a randomized controlled trial, they found that chatbot-assisted dietary advice with brief guidance effectively reduced high FODMAP intake, bloating severity, and improved dietary knowledge, particularly in patients with bothersome bloating.
“Chatbot-assisted dietary advice for FODMAPs restriction was feasible and applicable in patients with bloating symptoms that had baseline symptoms of moderate severity,” study chief Pochara Somvanapanich, with the Division of Gastroenterology, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand, told GI & Hepatology News.
Somvanapanich, who developed the chatbot algorithm, presented the study results at Digestive Disease Week (DDW) 2025.
More Knowledge, Less Bloating
The trial enrolled 86 adults with disorders of gut-brain interaction experiencing bloating symptoms for more than 6 months and consuming more than seven high-FODMAPs items per week. Half of them had IBS.
At baseline, gastrointestinal (GI) symptoms and the ability to identify FODMAPs were assessed. All participants received a 5-minute consultation on FODMAPs avoidance from a GI fellow and were randomly allocated (stratified by IBS diagnosis and education) into two groups.
The chatbot-assisted group received real-time dietary advice via a chatbot which helped them identify high, low, and non-FODMAP foods from a list of more than 300 ingredients/dishes of Thai and western cuisines.
The control group received only brief advice on high FODMAPs restriction. Both groups used a diary app to log food intake and postprandial symptoms. Baseline bloating, abdominal pain and global symptoms severity were similar between the two groups. Data on 64 participants (32 in each group) were analyzed.
After 4 weeks, significantly more people in the chatbot group than the control group responded — achieving a 30% or greater reduction in daily worst bloating, abdominal pain or global symptoms (19 [59%] vs 10 [31%], P < .05). Responder rates were similar in the IBS and non-IBS subgroups.
Subgroup analysis revealed significant differences between groups only for participants with bothersome bloating, not those with mild bloating severity.
In those with bothersome bloating severity, the chatbot group had a higher response rate (69.5% vs 36.3%) and fewer bloating symptoms (P < .05). They also had a greater reduction in high FODMAPs intake (10 vs 23 items/week) and demonstrated improved knowledge in identifying FODMAPs (P < .05).
“Responders in a chatbot group consistently engaged more with the app, performing significantly more weekly item searches than nonresponders (P < .05),” the authors noted in their conference abstract.
“Our next step is to develop the chatbot-assisted approach for the reintroduction and personalization phase based on messenger applications (including Facebook Messenger and other messaging platforms),” Somvanapanich told GI & Hepatology News.
“Once we’ve gathered enough data to confirm these are working effectively, we definitely plan to create a one-stop service application for FODMAPs dietary advice,” Somvanapanich added.
Lack of Robust Data on Digital GI Health Apps
Commenting on this research for GI & Hepatology News, Sidhartha R. Sinha, MD, Director of Digital Health and Innovation, Division of Gastroenterology and Hepatology, Stanford University in Stanford, California, noted that there is a “notable lack of robust data supporting digital health tools in gastroenterology. Despite hundreds of apps available, very few are supported by well-designed trials.”
“The study demonstrated that chatbot-assisted dietary advice significantly improved bloating symptoms, reduced intake of high-FODMAP foods, and enhanced patients’ dietary knowledge compared to brief dietary counseling alone, especially in those with bothersome symptoms,” said Sinha, who wasn’t involved in the study.
“Patients actively used the chatbot to manage their symptoms, achieving a higher response rate than those in the control arm who received brief counseling on avoiding high-FODMAP food,” he noted.
Sinha said in his practice at Stanford, “in the heart of Silicon Valley,” patients do use digital resources to manage their GI symptoms, including diseases like IBS and inflammatory bowel disease (IBD) — and he believes this is “increasingly common nationally.”
“However, the need for evidence-based tools is critical and the lack here often prevents many practitioners from regularly recommending them to patients. This study aligns well with clinical practice, and supports the use of this particular app to improve IBS symptoms, particularly when access to dietitians is limited. These results support chatbot-assisted dietary management as a feasible, effective, and scalable approach to patient care,” Sinha told GI & Hepatology News.
The study received no commercial funding. Somvanapanich and Sinha had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Blood-Based Test May Predict Crohn’s Disease 2 Years Before Onset
SAN DIEGO — Crohn’s disease (CD) has become more common in the United States, and an estimated 1 million Americans have the condition. Still, much is unknown about how to evaluate the individual risk for the disease.
“It’s pretty much accepted that Crohn’s disease does not begin at diagnosis,” said Ryan Ungaro, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai, New York City, speaking at Digestive Disease Week (DDW)® 2025.
Although individual blood markers have been associated with the future risk for CD, what’s needed, he said, is to understand which combination of biomarkers are most predictive.
Now, .
It’s an early version that will likely be further improved and needs additional validation, Ungaro told GI & Hepatology News.
“Once we can accurately identify individuals at risk for developing Crohn’s disease, we can then imagine a number of potential interventions,” Ungaro said.
Approaches would vary depending on how far away the onset is estimated to be. For people who likely wouldn’t develop disease for many years, one intervention might be close monitoring to enable diagnosis in the earliest stages, when treatment works best, he said. Someone at a high risk of developing CD in the next 2 or 3 years, on the other hand, might be offered a pharmaceutical intervention.
Developing and Testing the Risk Score
To develop the risk score, Ungaro and colleagues analyzed data of 200 patients with CD and 100 healthy control participants from PREDICTS, a nested case-controlled study of active US military service members. The study is within the larger Department of Defense Serum Repository, which began in 1985 and has more than 62.5 million samples, all stored at −30 °C.
The researchers collected serum samples at four timepoints up to 6 or more years before the diagnosis. They assayed antimicrobial antibodies using the Prometheus Laboratories platform, proteomic markers using the Olink inflammation panel, and anti–granulocyte macrophage colony-stimulating factor autoantibodies using enzyme-linked immunosorbent assay.
Participants (median age, 33 years for both groups) were randomly divided into equally sized training and testing sets. In both the group, 83% of patients were White and about 90% were men.
Time-varying trajectories of marker abundance were estimated for each biomarker. Then, logistic regression modeled disease status as a function of each marker for different timepoints and multivariate modeling was performed via logistic LASSO regression.
A risk score to predict CD onset within 2 years was developed. Prediction models were fit on the testing set and predictive performance evaluated using receiver operating characteristic curves and area under the curve (AUC).
Blood proteins and antibodies have differing associations with CD depending on the time before diagnosis, the researchers found.
The integrative model to predict CD onset within 2 years incorporated 10 biomarkers associated significantly with CD onset.
The AUC for the model was 0.87 (considered good, with 1 indicating perfect discrimination). It produced a specificity of 99% and a positive predictive value of 84%.
The researchers stratified the model scores into quartiles and found the CD incidence within 2 years increased from 2% in the first quartile to 57.7% in the fourth. The relative risk of developing CD in the top quartile individuals vs lower quartile individuals was 10.4.
The serologic and proteomic markers show dynamic changes years before the diagnosis, Ungaro said.
A Strong Start
The research represents “an ambitious and exciting frontier for the future of IBD [inflammatory bowel disease] care,” said Victor G. Chedid, MD, MS, consultant and assistant professor of medicine at Mayo Clinic, Rochester, Minnesota, who reviewed the findings but was not involved in the study.
Currently, physicians treat IBD once it manifests, and it’s difficult to predict who will get CD, he said.
The integrative model’s AUC of 0.87 is impressive, and its specificity and positive predictive value levels show it is highly accurate in predicting the onset of CD within 2 years, Chedid added.
Further validation in larger and more diverse population is needed, Chedid said, but he sees the potential for the model to be practical in clinical practice.
“Additionally, the use of blood-based biomarkers makes the model relatively noninvasive and easy to implement in a clinical setting,” he said.
Now, the research goal is to understand the best biomarkers for characterizing the different preclinical phases of CD and to test different interventions in prevention trials, Ungaro told GI & Hepatology News.
A few trials are planned or ongoing, he noted. The trial PIONIR trial will look at the impact of a specific diet on the risk of developing CD, and the INTERCEPT trial aims to develop a blood-based risk score that can identify individuals with a high risk of developing CD within 5 years after initial evaluation.
Ungaro reported being on the advisory board of and/or receiving speaker or consulting fees from AbbVie, Bristol Myer Squibb, Celltrion, ECM Therapeutics, Genentech, Jansen, Eli Lilly, Pfizer, Roivant, Sanofi, and Takeda. Chedid reported having no relevant disclosures.
The PROMISE Consortium is funded by the Helmsley Charitable Trust.
A version of this article appeared on Medscape.com.
SAN DIEGO — Crohn’s disease (CD) has become more common in the United States, and an estimated 1 million Americans have the condition. Still, much is unknown about how to evaluate the individual risk for the disease.
“It’s pretty much accepted that Crohn’s disease does not begin at diagnosis,” said Ryan Ungaro, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai, New York City, speaking at Digestive Disease Week (DDW)® 2025.
Although individual blood markers have been associated with the future risk for CD, what’s needed, he said, is to understand which combination of biomarkers are most predictive.
Now, .
It’s an early version that will likely be further improved and needs additional validation, Ungaro told GI & Hepatology News.
“Once we can accurately identify individuals at risk for developing Crohn’s disease, we can then imagine a number of potential interventions,” Ungaro said.
Approaches would vary depending on how far away the onset is estimated to be. For people who likely wouldn’t develop disease for many years, one intervention might be close monitoring to enable diagnosis in the earliest stages, when treatment works best, he said. Someone at a high risk of developing CD in the next 2 or 3 years, on the other hand, might be offered a pharmaceutical intervention.
Developing and Testing the Risk Score
To develop the risk score, Ungaro and colleagues analyzed data of 200 patients with CD and 100 healthy control participants from PREDICTS, a nested case-controlled study of active US military service members. The study is within the larger Department of Defense Serum Repository, which began in 1985 and has more than 62.5 million samples, all stored at −30 °C.
The researchers collected serum samples at four timepoints up to 6 or more years before the diagnosis. They assayed antimicrobial antibodies using the Prometheus Laboratories platform, proteomic markers using the Olink inflammation panel, and anti–granulocyte macrophage colony-stimulating factor autoantibodies using enzyme-linked immunosorbent assay.
Participants (median age, 33 years for both groups) were randomly divided into equally sized training and testing sets. In both the group, 83% of patients were White and about 90% were men.
Time-varying trajectories of marker abundance were estimated for each biomarker. Then, logistic regression modeled disease status as a function of each marker for different timepoints and multivariate modeling was performed via logistic LASSO regression.
A risk score to predict CD onset within 2 years was developed. Prediction models were fit on the testing set and predictive performance evaluated using receiver operating characteristic curves and area under the curve (AUC).
Blood proteins and antibodies have differing associations with CD depending on the time before diagnosis, the researchers found.
The integrative model to predict CD onset within 2 years incorporated 10 biomarkers associated significantly with CD onset.
The AUC for the model was 0.87 (considered good, with 1 indicating perfect discrimination). It produced a specificity of 99% and a positive predictive value of 84%.
The researchers stratified the model scores into quartiles and found the CD incidence within 2 years increased from 2% in the first quartile to 57.7% in the fourth. The relative risk of developing CD in the top quartile individuals vs lower quartile individuals was 10.4.
The serologic and proteomic markers show dynamic changes years before the diagnosis, Ungaro said.
A Strong Start
The research represents “an ambitious and exciting frontier for the future of IBD [inflammatory bowel disease] care,” said Victor G. Chedid, MD, MS, consultant and assistant professor of medicine at Mayo Clinic, Rochester, Minnesota, who reviewed the findings but was not involved in the study.
Currently, physicians treat IBD once it manifests, and it’s difficult to predict who will get CD, he said.
The integrative model’s AUC of 0.87 is impressive, and its specificity and positive predictive value levels show it is highly accurate in predicting the onset of CD within 2 years, Chedid added.
Further validation in larger and more diverse population is needed, Chedid said, but he sees the potential for the model to be practical in clinical practice.
“Additionally, the use of blood-based biomarkers makes the model relatively noninvasive and easy to implement in a clinical setting,” he said.
Now, the research goal is to understand the best biomarkers for characterizing the different preclinical phases of CD and to test different interventions in prevention trials, Ungaro told GI & Hepatology News.
A few trials are planned or ongoing, he noted. The trial PIONIR trial will look at the impact of a specific diet on the risk of developing CD, and the INTERCEPT trial aims to develop a blood-based risk score that can identify individuals with a high risk of developing CD within 5 years after initial evaluation.
Ungaro reported being on the advisory board of and/or receiving speaker or consulting fees from AbbVie, Bristol Myer Squibb, Celltrion, ECM Therapeutics, Genentech, Jansen, Eli Lilly, Pfizer, Roivant, Sanofi, and Takeda. Chedid reported having no relevant disclosures.
The PROMISE Consortium is funded by the Helmsley Charitable Trust.
A version of this article appeared on Medscape.com.
SAN DIEGO — Crohn’s disease (CD) has become more common in the United States, and an estimated 1 million Americans have the condition. Still, much is unknown about how to evaluate the individual risk for the disease.
“It’s pretty much accepted that Crohn’s disease does not begin at diagnosis,” said Ryan Ungaro, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai, New York City, speaking at Digestive Disease Week (DDW)® 2025.
Although individual blood markers have been associated with the future risk for CD, what’s needed, he said, is to understand which combination of biomarkers are most predictive.
Now, .
It’s an early version that will likely be further improved and needs additional validation, Ungaro told GI & Hepatology News.
“Once we can accurately identify individuals at risk for developing Crohn’s disease, we can then imagine a number of potential interventions,” Ungaro said.
Approaches would vary depending on how far away the onset is estimated to be. For people who likely wouldn’t develop disease for many years, one intervention might be close monitoring to enable diagnosis in the earliest stages, when treatment works best, he said. Someone at a high risk of developing CD in the next 2 or 3 years, on the other hand, might be offered a pharmaceutical intervention.
Developing and Testing the Risk Score
To develop the risk score, Ungaro and colleagues analyzed data of 200 patients with CD and 100 healthy control participants from PREDICTS, a nested case-controlled study of active US military service members. The study is within the larger Department of Defense Serum Repository, which began in 1985 and has more than 62.5 million samples, all stored at −30 °C.
The researchers collected serum samples at four timepoints up to 6 or more years before the diagnosis. They assayed antimicrobial antibodies using the Prometheus Laboratories platform, proteomic markers using the Olink inflammation panel, and anti–granulocyte macrophage colony-stimulating factor autoantibodies using enzyme-linked immunosorbent assay.
Participants (median age, 33 years for both groups) were randomly divided into equally sized training and testing sets. In both the group, 83% of patients were White and about 90% were men.
Time-varying trajectories of marker abundance were estimated for each biomarker. Then, logistic regression modeled disease status as a function of each marker for different timepoints and multivariate modeling was performed via logistic LASSO regression.
A risk score to predict CD onset within 2 years was developed. Prediction models were fit on the testing set and predictive performance evaluated using receiver operating characteristic curves and area under the curve (AUC).
Blood proteins and antibodies have differing associations with CD depending on the time before diagnosis, the researchers found.
The integrative model to predict CD onset within 2 years incorporated 10 biomarkers associated significantly with CD onset.
The AUC for the model was 0.87 (considered good, with 1 indicating perfect discrimination). It produced a specificity of 99% and a positive predictive value of 84%.
The researchers stratified the model scores into quartiles and found the CD incidence within 2 years increased from 2% in the first quartile to 57.7% in the fourth. The relative risk of developing CD in the top quartile individuals vs lower quartile individuals was 10.4.
The serologic and proteomic markers show dynamic changes years before the diagnosis, Ungaro said.
A Strong Start
The research represents “an ambitious and exciting frontier for the future of IBD [inflammatory bowel disease] care,” said Victor G. Chedid, MD, MS, consultant and assistant professor of medicine at Mayo Clinic, Rochester, Minnesota, who reviewed the findings but was not involved in the study.
Currently, physicians treat IBD once it manifests, and it’s difficult to predict who will get CD, he said.
The integrative model’s AUC of 0.87 is impressive, and its specificity and positive predictive value levels show it is highly accurate in predicting the onset of CD within 2 years, Chedid added.
Further validation in larger and more diverse population is needed, Chedid said, but he sees the potential for the model to be practical in clinical practice.
“Additionally, the use of blood-based biomarkers makes the model relatively noninvasive and easy to implement in a clinical setting,” he said.
Now, the research goal is to understand the best biomarkers for characterizing the different preclinical phases of CD and to test different interventions in prevention trials, Ungaro told GI & Hepatology News.
A few trials are planned or ongoing, he noted. The trial PIONIR trial will look at the impact of a specific diet on the risk of developing CD, and the INTERCEPT trial aims to develop a blood-based risk score that can identify individuals with a high risk of developing CD within 5 years after initial evaluation.
Ungaro reported being on the advisory board of and/or receiving speaker or consulting fees from AbbVie, Bristol Myer Squibb, Celltrion, ECM Therapeutics, Genentech, Jansen, Eli Lilly, Pfizer, Roivant, Sanofi, and Takeda. Chedid reported having no relevant disclosures.
The PROMISE Consortium is funded by the Helmsley Charitable Trust.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Precision-Medicine Approach Improves IBD Infliximab Outcomes
SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.
“,” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.
“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.
Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.
In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.
“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.
Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.
To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.
All patients had been assigned the anti-TNF drug infliximab for the first time.
Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.
Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.
The assessments also looked at infliximab and anti-drug antibody levels.
Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.
Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.
The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).
A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.
For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).
Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).
An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.
More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).
“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.
The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.
Approach Pioneered in Oncology
Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.
“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.
Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.
The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.”
Benefits in Other IBD Therapies Unclear
Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”
Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”
While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.
“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.
How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.
Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.
A version of this article appeared on Medscape.com.
SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.
“,” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.
“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.
Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.
In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.
“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.
Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.
To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.
All patients had been assigned the anti-TNF drug infliximab for the first time.
Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.
Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.
The assessments also looked at infliximab and anti-drug antibody levels.
Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.
Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.
The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).
A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.
For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).
Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).
An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.
More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).
“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.
The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.
Approach Pioneered in Oncology
Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.
“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.
Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.
The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.”
Benefits in Other IBD Therapies Unclear
Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”
Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”
While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.
“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.
How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.
Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.
A version of this article appeared on Medscape.com.
SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.
“,” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.
“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.
Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.
In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.
“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.
Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.
To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.
All patients had been assigned the anti-TNF drug infliximab for the first time.
Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.
Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.
The assessments also looked at infliximab and anti-drug antibody levels.
Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.
Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.
The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).
A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.
For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).
Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).
An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.
More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).
“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.
The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.
Approach Pioneered in Oncology
Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.
“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.
Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.
The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.”
Benefits in Other IBD Therapies Unclear
Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”
Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”
While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.
“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.
How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.
Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.
A version of this article appeared on Medscape.com.
FROM DDW 2025
IgG-Guided Elimination Diet Beats Sham Diet for IBS Pain
An irritable bowel syndrome (IBS) elimination diet based on a novel IBS–specific, immunoglobulin G (IgG) was superior to a sham diet for abdominal pain, an 8-center, randomized double-blind controlled trial found.
While elimination diets can provide a personalized approach to dietary therapy, existing studies have had serious methodological issues, noted lead author Prashant Singh, MBBS, of the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Mich., and colleagues in Gastroenterology.
For example, previous studies on IgG-based diets used assays developed without determining IBS trigger foods or establishing a 95% confidence interval–based cutoff using a healthy control comparison group.
Study Details
From June 2018 to December 2021, 238 IBS patients testing positive for at least one food on 18-food IgG ELISA (enzyme-linked immunosorbent assay) testing and an average daily abdominal pain intensity score of 3.0 to 7.5 on an 11.0-point scale during a 2-week run-in period were randomized for 8 weeks to an experimental antibody-guided diet or to a sham diet. The primary outcome was a 30% decrease in abdominal pain intensity (API) for 2 of the last 4 weeks of treatment.
The overall study population had a mean age of about 40 years, and more than three-quarters were female. The 3 IBS types – constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), and mixed bowel habits-predominant (IBS-M) – accounted for about a third each in both arms.
The experimental diet eliminated foods based on a positive ELISA result. Its sham counterpart had the same number of foods removed as the number of positive-testing food sensitivities, but the foods eliminated in the sham diet had tested negative on the IgG assay.
Participants reported daily abdominal pain intensity, bloating, and stool consistency, and frequency. They also reported dietary compliance and daily medication use.
Of the 238 randomized adults, 223 were included in the modified intention-to-treat analysis. A significantly greater proportion of subjects in the experimental group met the primary outcome than those in the sham group: 59.6% vs 42.1%, P = .02). “This highlights the potential effectiveness of a personalized elimination diet based on a novel IBS-specific IgG assay,” the authors wrote.
Symptom improvement between arms began to separate out at around 2 weeks, suggesting the effect of the experimental diet was relatively rapid in onset, and continued for at least 8 weeks. The durability of response, however, needs to be assessed in future studies “and it is unclear if there is a role for repeat IgG testing to monitor treatment response,” the authors wrote.
Subgroup analysis revealed that a higher proportion of those with IBS-C and IBS-M in the experimental diet group met the primary endpoint vs the sham group: 67.1% vs 35.8% and 66% vs 29.5%, respectively.
Interestingly, more patients in the experimental arm were noncompliant with their diet. “It is possible that subjects found the experimental diet more difficult to comply with compared with the sham diet or that because the experimental diet was more likely to improve symptoms, dietary indiscretion may have been more common in this group (a phenomenon seen with other elimination diets such as gluten-free diet in celiac disease),” the authors wrote.
Adverse events, deemed unrelated to either regimen, were 3 in the experimental arm vs 8 in the sham arm, which had 2 urinary tract infections.
The authors called for a larger, adequately powered study to assess the efficacy of an elimination diet based on this novel immunoglobulin G assay in patients with IBS-C and IBS-M. Future studies should perform detailed adherence assessments using food diaries.
“Mechanisms of how immunoglobulin G-antibody response to food antigen generates symptoms in irritable bowel syndrome are not well understood. Delineating this might provide new insights into food-related irritable bowel syndrome pathophysiology,” they concluded.
This study was funded by Biomerica Inc.
Symptoms in most people with irritable bowel syndrome (IBS) are perceived to be closely linked to diet. The low FODMAP diet has been pivotal for the treatment of IBS, and a range of other diet approaches are now on the research horizon.
Whilst IgE-mediated allergy is relatively rare, there has been research suggesting a role of IgG-mediated food sensitivity in causing symptoms in IBS, although the role of IgG testing and dietary elimination has been controversial. This study from Singh and colleagues suggests an IgG-based elimination diet could improve abdominal pain and global symptoms in two thirds of people with Rome IV IBS. Critically, the study is one of the largest so far and provides the most robust and detailed description of the trial diets to date.
The potential of a new diet approach is extremely appealing, especially as the low FODMAP diet is not universally effective. However, there is still some work to be done to transition the IgG-based elimination diet into guidelines and routine practice. Notably, some common foods restricted in IgG-based elimination diets are also high in FODMAPs leaving questions about the true driver of symptom benefit. Should convincing mechanistic studies and further additional RCT data validate these findings, this could present a major step forward for personalised nutrition in IBS.
Heidi Staudacher, PhD, is associate professor in the School of Translational Medicine, Monash University, Melbourne, Australia. She declared no conflicts of interest.
Symptoms in most people with irritable bowel syndrome (IBS) are perceived to be closely linked to diet. The low FODMAP diet has been pivotal for the treatment of IBS, and a range of other diet approaches are now on the research horizon.
Whilst IgE-mediated allergy is relatively rare, there has been research suggesting a role of IgG-mediated food sensitivity in causing symptoms in IBS, although the role of IgG testing and dietary elimination has been controversial. This study from Singh and colleagues suggests an IgG-based elimination diet could improve abdominal pain and global symptoms in two thirds of people with Rome IV IBS. Critically, the study is one of the largest so far and provides the most robust and detailed description of the trial diets to date.
The potential of a new diet approach is extremely appealing, especially as the low FODMAP diet is not universally effective. However, there is still some work to be done to transition the IgG-based elimination diet into guidelines and routine practice. Notably, some common foods restricted in IgG-based elimination diets are also high in FODMAPs leaving questions about the true driver of symptom benefit. Should convincing mechanistic studies and further additional RCT data validate these findings, this could present a major step forward for personalised nutrition in IBS.
Heidi Staudacher, PhD, is associate professor in the School of Translational Medicine, Monash University, Melbourne, Australia. She declared no conflicts of interest.
Symptoms in most people with irritable bowel syndrome (IBS) are perceived to be closely linked to diet. The low FODMAP diet has been pivotal for the treatment of IBS, and a range of other diet approaches are now on the research horizon.
Whilst IgE-mediated allergy is relatively rare, there has been research suggesting a role of IgG-mediated food sensitivity in causing symptoms in IBS, although the role of IgG testing and dietary elimination has been controversial. This study from Singh and colleagues suggests an IgG-based elimination diet could improve abdominal pain and global symptoms in two thirds of people with Rome IV IBS. Critically, the study is one of the largest so far and provides the most robust and detailed description of the trial diets to date.
The potential of a new diet approach is extremely appealing, especially as the low FODMAP diet is not universally effective. However, there is still some work to be done to transition the IgG-based elimination diet into guidelines and routine practice. Notably, some common foods restricted in IgG-based elimination diets are also high in FODMAPs leaving questions about the true driver of symptom benefit. Should convincing mechanistic studies and further additional RCT data validate these findings, this could present a major step forward for personalised nutrition in IBS.
Heidi Staudacher, PhD, is associate professor in the School of Translational Medicine, Monash University, Melbourne, Australia. She declared no conflicts of interest.
An irritable bowel syndrome (IBS) elimination diet based on a novel IBS–specific, immunoglobulin G (IgG) was superior to a sham diet for abdominal pain, an 8-center, randomized double-blind controlled trial found.
While elimination diets can provide a personalized approach to dietary therapy, existing studies have had serious methodological issues, noted lead author Prashant Singh, MBBS, of the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Mich., and colleagues in Gastroenterology.
For example, previous studies on IgG-based diets used assays developed without determining IBS trigger foods or establishing a 95% confidence interval–based cutoff using a healthy control comparison group.
Study Details
From June 2018 to December 2021, 238 IBS patients testing positive for at least one food on 18-food IgG ELISA (enzyme-linked immunosorbent assay) testing and an average daily abdominal pain intensity score of 3.0 to 7.5 on an 11.0-point scale during a 2-week run-in period were randomized for 8 weeks to an experimental antibody-guided diet or to a sham diet. The primary outcome was a 30% decrease in abdominal pain intensity (API) for 2 of the last 4 weeks of treatment.
The overall study population had a mean age of about 40 years, and more than three-quarters were female. The 3 IBS types – constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), and mixed bowel habits-predominant (IBS-M) – accounted for about a third each in both arms.
The experimental diet eliminated foods based on a positive ELISA result. Its sham counterpart had the same number of foods removed as the number of positive-testing food sensitivities, but the foods eliminated in the sham diet had tested negative on the IgG assay.
Participants reported daily abdominal pain intensity, bloating, and stool consistency, and frequency. They also reported dietary compliance and daily medication use.
Of the 238 randomized adults, 223 were included in the modified intention-to-treat analysis. A significantly greater proportion of subjects in the experimental group met the primary outcome than those in the sham group: 59.6% vs 42.1%, P = .02). “This highlights the potential effectiveness of a personalized elimination diet based on a novel IBS-specific IgG assay,” the authors wrote.
Symptom improvement between arms began to separate out at around 2 weeks, suggesting the effect of the experimental diet was relatively rapid in onset, and continued for at least 8 weeks. The durability of response, however, needs to be assessed in future studies “and it is unclear if there is a role for repeat IgG testing to monitor treatment response,” the authors wrote.
Subgroup analysis revealed that a higher proportion of those with IBS-C and IBS-M in the experimental diet group met the primary endpoint vs the sham group: 67.1% vs 35.8% and 66% vs 29.5%, respectively.
Interestingly, more patients in the experimental arm were noncompliant with their diet. “It is possible that subjects found the experimental diet more difficult to comply with compared with the sham diet or that because the experimental diet was more likely to improve symptoms, dietary indiscretion may have been more common in this group (a phenomenon seen with other elimination diets such as gluten-free diet in celiac disease),” the authors wrote.
Adverse events, deemed unrelated to either regimen, were 3 in the experimental arm vs 8 in the sham arm, which had 2 urinary tract infections.
The authors called for a larger, adequately powered study to assess the efficacy of an elimination diet based on this novel immunoglobulin G assay in patients with IBS-C and IBS-M. Future studies should perform detailed adherence assessments using food diaries.
“Mechanisms of how immunoglobulin G-antibody response to food antigen generates symptoms in irritable bowel syndrome are not well understood. Delineating this might provide new insights into food-related irritable bowel syndrome pathophysiology,” they concluded.
This study was funded by Biomerica Inc.
An irritable bowel syndrome (IBS) elimination diet based on a novel IBS–specific, immunoglobulin G (IgG) was superior to a sham diet for abdominal pain, an 8-center, randomized double-blind controlled trial found.
While elimination diets can provide a personalized approach to dietary therapy, existing studies have had serious methodological issues, noted lead author Prashant Singh, MBBS, of the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Mich., and colleagues in Gastroenterology.
For example, previous studies on IgG-based diets used assays developed without determining IBS trigger foods or establishing a 95% confidence interval–based cutoff using a healthy control comparison group.
Study Details
From June 2018 to December 2021, 238 IBS patients testing positive for at least one food on 18-food IgG ELISA (enzyme-linked immunosorbent assay) testing and an average daily abdominal pain intensity score of 3.0 to 7.5 on an 11.0-point scale during a 2-week run-in period were randomized for 8 weeks to an experimental antibody-guided diet or to a sham diet. The primary outcome was a 30% decrease in abdominal pain intensity (API) for 2 of the last 4 weeks of treatment.
The overall study population had a mean age of about 40 years, and more than three-quarters were female. The 3 IBS types – constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), and mixed bowel habits-predominant (IBS-M) – accounted for about a third each in both arms.
The experimental diet eliminated foods based on a positive ELISA result. Its sham counterpart had the same number of foods removed as the number of positive-testing food sensitivities, but the foods eliminated in the sham diet had tested negative on the IgG assay.
Participants reported daily abdominal pain intensity, bloating, and stool consistency, and frequency. They also reported dietary compliance and daily medication use.
Of the 238 randomized adults, 223 were included in the modified intention-to-treat analysis. A significantly greater proportion of subjects in the experimental group met the primary outcome than those in the sham group: 59.6% vs 42.1%, P = .02). “This highlights the potential effectiveness of a personalized elimination diet based on a novel IBS-specific IgG assay,” the authors wrote.
Symptom improvement between arms began to separate out at around 2 weeks, suggesting the effect of the experimental diet was relatively rapid in onset, and continued for at least 8 weeks. The durability of response, however, needs to be assessed in future studies “and it is unclear if there is a role for repeat IgG testing to monitor treatment response,” the authors wrote.
Subgroup analysis revealed that a higher proportion of those with IBS-C and IBS-M in the experimental diet group met the primary endpoint vs the sham group: 67.1% vs 35.8% and 66% vs 29.5%, respectively.
Interestingly, more patients in the experimental arm were noncompliant with their diet. “It is possible that subjects found the experimental diet more difficult to comply with compared with the sham diet or that because the experimental diet was more likely to improve symptoms, dietary indiscretion may have been more common in this group (a phenomenon seen with other elimination diets such as gluten-free diet in celiac disease),” the authors wrote.
Adverse events, deemed unrelated to either regimen, were 3 in the experimental arm vs 8 in the sham arm, which had 2 urinary tract infections.
The authors called for a larger, adequately powered study to assess the efficacy of an elimination diet based on this novel immunoglobulin G assay in patients with IBS-C and IBS-M. Future studies should perform detailed adherence assessments using food diaries.
“Mechanisms of how immunoglobulin G-antibody response to food antigen generates symptoms in irritable bowel syndrome are not well understood. Delineating this might provide new insights into food-related irritable bowel syndrome pathophysiology,” they concluded.
This study was funded by Biomerica Inc.
FROM GASTROENTEROLOGY