From the AGA Journals

Large nonpedunculated rectal polyps (LNPRPs), defined as 20 mm or larger, are associated with a high risk of submucosal invasive cancer (SMIC). Although LNPRPs can be removed by distal colorectal surgery, this approach has an increased risk of morbidity, mortality, and permanent ostomy formation.

The first-line resection technique for LNPRPs is endoscopic mucosal resection (EMR); however, for larger lesions, piecemeal removal is required. When SMIC is revealed after piecemeal resection, surgery is generally recommended, since this is the only way to determine if R0 margins and curative oncologic resection have been achieved.

In such cases, an alternative is endoscopic submucosal dissection (ESD), but there is no current algorithm to choose between the two procedures based on lesion identity.

Optical methods can determine a lesion’s pit and microvascular pattern in real time to determine if SMIC is present, but the performance is modest. Researchers sought to bolster optical detection by combining it with SMIC risk stratification to streamline the choice between EMR and ESD for LNPRPs.

In a study published online in Clinical Gastroenterology and Hepatology, researchers led by Neal Shahidi, MD, of the division of gastroenterology, St. Paul’s Hospital, Vancouver, described a selective resection algorithm (SRA) that could assist gastroenterologists in determining the best procedure to use when confronted with an LNPRP.

“Cost-effectiveness analyses have shown that an SRA using EMR and ESD is the optimal approach. However, a mechanism to facilitate modality selection has not been delineated. To our knowledge, this study is the first to show that a rectum-specific SRA, based on real-time optical evaluation and covert SMIC risk stratification, increases the frequency of curative oncologic resection and minimizes the risk of piecemeal resection of malignant LNPRPs. ... Piecemeal resection of endoscopically curable malignant LNPRPs negates the very benefit that they are intended to provide. To avoid malignant piecemeal resection, optical evaluation of the lesion’s pit and microvascular surface pattern can be used to predict SMIC prior to resection technique selection,” the authors wrote.

The researchers conducted a prospective observational study of 480 LNPRPs that were detected between July 2008 and April 2021. They compared the performance of the SRA to that of a universal EMR algorithm (UEA) for procedure determination. The SRA flagged LNPRPs with features consistent with SMIC (< 1,000 mm or Kudo pit pattern Vi) for endoscopic dissection. The latter included Paris 0-Is or 0-IIa+Is nongranular, or 0-IIa+Is granular with a dominant nodule 10 mm or larger. Other LNPRPs were designated to undergo EMR.

The median patient age was 67 years, and 54.2% were men; 90.1% of participants were ASA I-II; 290 LNPRPs were evaluated with the UEA and 190 with the SRA. The median lesion size was 40 mm. Overall, 11.7% of LPNRPs were identified as containing SMIC.

In the SRA, only 1.0% of LNPRPs removed by EMR contained SMIC, while the UEA identified cancer in 12.1%, a significant difference (P = .001). The SRA led to 33.3% as curative oncologic resections, while the UEA achieved only 5.7% (P = .010).

There were no significant differences in technical success or adverse events between the two algorithms.

Procedures determined by SRA took longer than those decided by UEA (median resection duration, 45 vs. 29 minutes; P < .001). Among LNPRPs that were removed through EMR and margin thermal ablation, there was no significant difference in recurrence whether SRA or UEA was used to determine the procedure.

Compared with UEA, SRA was associated with higher rates of en bloc resection (90.5% vs. 11.4%; P < .001), R0 resection (85.7% vs. 5.7%; P < .001), and curative oncologic resection (33.3% vs. 5.7%; P = .010).

“In this study, using analogous optical evaluation and covert SMIC risk stratification criteria, only one (1.0%) [of] malignant LNPRP underwent piecemeal resection within the SRA. This is a pivotal advance in the application of minimally invasive endoscopic resection techniques. It demonstrates an effective approach to optical evaluation; thereby, delineating which LNPRPs can be effectively, efficiently, and safely managed by EMR, compared with those which may derive benefit from ESD,” the authors wrote.

The authors recommended ESD only be used for lesions with suspected superficial SMIC or when there is a heightened risk of SMIC.

A key finding of the study is the frequency of curative resection following ESD. “At 33.3%, this represents a critical improvement in patient outcomes and the application of minimally invasive endoscopic resection techniques; especially when taking into consideration the potential negative ramifications of distal colorectal surgery and evidence showing that endoscopic resection does not impair subsequent surgical intervention,” the authors wrote.

There was no significant difference in recurrence at surveillance colonoscopy between SRA and UEA when undergoing margin thermal ablation. The finding suggests that margin thermal ablation should be considered a vital component of EMR, according to the authors.

Dr. Shahidi received speaker honorarium from Boston Scientific and Pharmascience, and one coauthor received research support from Olympus, Cook Medical, and Boston Scientific.

Large nonpedunculated rectal polyps (LNPRPs), defined as 20 mm or larger, are associated with a high risk of submucosal invasive cancer (SMIC). Although LNPRPs can be removed by distal colorectal surgery, this approach has an increased risk of morbidity, mortality, and permanent ostomy formation.

The first-line resection technique for LNPRPs is endoscopic mucosal resection (EMR); however, for larger lesions, piecemeal removal is required. When SMIC is revealed after piecemeal resection, surgery is generally recommended, since this is the only way to determine if R0 margins and curative oncologic resection have been achieved.

In such cases, an alternative is endoscopic submucosal dissection (ESD), but there is no current algorithm to choose between the two procedures based on lesion identity.

Optical methods can determine a lesion’s pit and microvascular pattern in real time to determine if SMIC is present, but the performance is modest. Researchers sought to bolster optical detection by combining it with SMIC risk stratification to streamline the choice between EMR and ESD for LNPRPs.

In a study published online in Clinical Gastroenterology and Hepatology, researchers led by Neal Shahidi, MD, of the division of gastroenterology, St. Paul’s Hospital, Vancouver, described a selective resection algorithm (SRA) that could assist gastroenterologists in determining the best procedure to use when confronted with an LNPRP.

“Cost-effectiveness analyses have shown that an SRA using EMR and ESD is the optimal approach. However, a mechanism to facilitate modality selection has not been delineated. To our knowledge, this study is the first to show that a rectum-specific SRA, based on real-time optical evaluation and covert SMIC risk stratification, increases the frequency of curative oncologic resection and minimizes the risk of piecemeal resection of malignant LNPRPs. ... Piecemeal resection of endoscopically curable malignant LNPRPs negates the very benefit that they are intended to provide. To avoid malignant piecemeal resection, optical evaluation of the lesion’s pit and microvascular surface pattern can be used to predict SMIC prior to resection technique selection,” the authors wrote.

The researchers conducted a prospective observational study of 480 LNPRPs that were detected between July 2008 and April 2021. They compared the performance of the SRA to that of a universal EMR algorithm (UEA) for procedure determination. The SRA flagged LNPRPs with features consistent with SMIC (< 1,000 mm or Kudo pit pattern Vi) for endoscopic dissection. The latter included Paris 0-Is or 0-IIa+Is nongranular, or 0-IIa+Is granular with a dominant nodule 10 mm or larger. Other LNPRPs were designated to undergo EMR.

The median patient age was 67 years, and 54.2% were men; 90.1% of participants were ASA I-II; 290 LNPRPs were evaluated with the UEA and 190 with the SRA. The median lesion size was 40 mm. Overall, 11.7% of LPNRPs were identified as containing SMIC.

In the SRA, only 1.0% of LNPRPs removed by EMR contained SMIC, while the UEA identified cancer in 12.1%, a significant difference (P = .001). The SRA led to 33.3% as curative oncologic resections, while the UEA achieved only 5.7% (P = .010).

There were no significant differences in technical success or adverse events between the two algorithms.

Procedures determined by SRA took longer than those decided by UEA (median resection duration, 45 vs. 29 minutes; P < .001). Among LNPRPs that were removed through EMR and margin thermal ablation, there was no significant difference in recurrence whether SRA or UEA was used to determine the procedure.

Compared with UEA, SRA was associated with higher rates of en bloc resection (90.5% vs. 11.4%; P < .001), R0 resection (85.7% vs. 5.7%; P < .001), and curative oncologic resection (33.3% vs. 5.7%; P = .010).

“In this study, using analogous optical evaluation and covert SMIC risk stratification criteria, only one (1.0%) [of] malignant LNPRP underwent piecemeal resection within the SRA. This is a pivotal advance in the application of minimally invasive endoscopic resection techniques. It demonstrates an effective approach to optical evaluation; thereby, delineating which LNPRPs can be effectively, efficiently, and safely managed by EMR, compared with those which may derive benefit from ESD,” the authors wrote.

The authors recommended ESD only be used for lesions with suspected superficial SMIC or when there is a heightened risk of SMIC.

A key finding of the study is the frequency of curative resection following ESD. “At 33.3%, this represents a critical improvement in patient outcomes and the application of minimally invasive endoscopic resection techniques; especially when taking into consideration the potential negative ramifications of distal colorectal surgery and evidence showing that endoscopic resection does not impair subsequent surgical intervention,” the authors wrote.

There was no significant difference in recurrence at surveillance colonoscopy between SRA and UEA when undergoing margin thermal ablation. The finding suggests that margin thermal ablation should be considered a vital component of EMR, according to the authors.

Dr. Shahidi received speaker honorarium from Boston Scientific and Pharmascience, and one coauthor received research support from Olympus, Cook Medical, and Boston Scientific.

Large nonpedunculated rectal polyps (LNPRPs), defined as 20 mm or larger, are associated with a high risk of submucosal invasive cancer (SMIC). Although LNPRPs can be removed by distal colorectal surgery, this approach has an increased risk of morbidity, mortality, and permanent ostomy formation.

The first-line resection technique for LNPRPs is endoscopic mucosal resection (EMR); however, for larger lesions, piecemeal removal is required. When SMIC is revealed after piecemeal resection, surgery is generally recommended, since this is the only way to determine if R0 margins and curative oncologic resection have been achieved.

In such cases, an alternative is endoscopic submucosal dissection (ESD), but there is no current algorithm to choose between the two procedures based on lesion identity.

Optical methods can determine a lesion’s pit and microvascular pattern in real time to determine if SMIC is present, but the performance is modest. Researchers sought to bolster optical detection by combining it with SMIC risk stratification to streamline the choice between EMR and ESD for LNPRPs.

In a study published online in Clinical Gastroenterology and Hepatology, researchers led by Neal Shahidi, MD, of the division of gastroenterology, St. Paul’s Hospital, Vancouver, described a selective resection algorithm (SRA) that could assist gastroenterologists in determining the best procedure to use when confronted with an LNPRP.

“Cost-effectiveness analyses have shown that an SRA using EMR and ESD is the optimal approach. However, a mechanism to facilitate modality selection has not been delineated. To our knowledge, this study is the first to show that a rectum-specific SRA, based on real-time optical evaluation and covert SMIC risk stratification, increases the frequency of curative oncologic resection and minimizes the risk of piecemeal resection of malignant LNPRPs. ... Piecemeal resection of endoscopically curable malignant LNPRPs negates the very benefit that they are intended to provide. To avoid malignant piecemeal resection, optical evaluation of the lesion’s pit and microvascular surface pattern can be used to predict SMIC prior to resection technique selection,” the authors wrote.

The researchers conducted a prospective observational study of 480 LNPRPs that were detected between July 2008 and April 2021. They compared the performance of the SRA to that of a universal EMR algorithm (UEA) for procedure determination. The SRA flagged LNPRPs with features consistent with SMIC (< 1,000 mm or Kudo pit pattern Vi) for endoscopic dissection. The latter included Paris 0-Is or 0-IIa+Is nongranular, or 0-IIa+Is granular with a dominant nodule 10 mm or larger. Other LNPRPs were designated to undergo EMR.

The median patient age was 67 years, and 54.2% were men; 90.1% of participants were ASA I-II; 290 LNPRPs were evaluated with the UEA and 190 with the SRA. The median lesion size was 40 mm. Overall, 11.7% of LPNRPs were identified as containing SMIC.

In the SRA, only 1.0% of LNPRPs removed by EMR contained SMIC, while the UEA identified cancer in 12.1%, a significant difference (P = .001). The SRA led to 33.3% as curative oncologic resections, while the UEA achieved only 5.7% (P = .010).

There were no significant differences in technical success or adverse events between the two algorithms.

Procedures determined by SRA took longer than those decided by UEA (median resection duration, 45 vs. 29 minutes; P < .001). Among LNPRPs that were removed through EMR and margin thermal ablation, there was no significant difference in recurrence whether SRA or UEA was used to determine the procedure.

Compared with UEA, SRA was associated with higher rates of en bloc resection (90.5% vs. 11.4%; P < .001), R0 resection (85.7% vs. 5.7%; P < .001), and curative oncologic resection (33.3% vs. 5.7%; P = .010).

“In this study, using analogous optical evaluation and covert SMIC risk stratification criteria, only one (1.0%) [of] malignant LNPRP underwent piecemeal resection within the SRA. This is a pivotal advance in the application of minimally invasive endoscopic resection techniques. It demonstrates an effective approach to optical evaluation; thereby, delineating which LNPRPs can be effectively, efficiently, and safely managed by EMR, compared with those which may derive benefit from ESD,” the authors wrote.

The authors recommended ESD only be used for lesions with suspected superficial SMIC or when there is a heightened risk of SMIC.

A key finding of the study is the frequency of curative resection following ESD. “At 33.3%, this represents a critical improvement in patient outcomes and the application of minimally invasive endoscopic resection techniques; especially when taking into consideration the potential negative ramifications of distal colorectal surgery and evidence showing that endoscopic resection does not impair subsequent surgical intervention,” the authors wrote.

There was no significant difference in recurrence at surveillance colonoscopy between SRA and UEA when undergoing margin thermal ablation. The finding suggests that margin thermal ablation should be considered a vital component of EMR, according to the authors.

Dr. Shahidi received speaker honorarium from Boston Scientific and Pharmascience, and one coauthor received research support from Olympus, Cook Medical, and Boston Scientific.

The oral potassium-competitive acid blocker (PCAB) vonoprazan was noninferior and superior to the proton-pump inhibitor (PPI) lansoprazole for erosive esophagitis, according to results of the phase 3 PHALCON-EE trial.

Vonoprazan achieved higher rates of healing and maintenance of healing than lansoprazole, with the benefit seen primarily in patients with more severe esophagitis.

The differences in healing rates were evident after 2 weeks of therapy and were maintained throughout the 24-week study, report Loren Laine, MD, Yale University, New Haven, Conn., and colleagues.

The study was published online in Gastroenterology.
 

More potent acid suppression

Gastroesophageal reflux disease is one of the most common disorders of the gastrointestinal tract, and erosive esophagitis is its most common complication.

Although standard PPI therapy is effective for healing erosive esophagitis, some patients do not achieve success with this conventional treatment.

Studies suggest that lack of healing of erosive esophagitis with 8 weeks of PPI therapy can be expected in roughly 5%-20% of patients, with rates up to 30% reported in patients with more severe esophagitis.

The PCAB vonoprazan provides more potent inhibition of gastric acid than PPIs and is seen as a potential alternative. However, data on its efficacy for erosive esophagitis are limited, the authors note.

The PHALCON-EE trial enrolled 1,024 adults from the United States and Europe with erosive esophagitis without Helicobacter pylori infection or Barrett esophagus.

Participants were randomized to receive once-daily vonoprazan 20 mg or lansoprazole 30 mg for up to 8 weeks in the healing phase.

The 878 patients with healing were then rerandomized to receive once-daily vonoprazan 10 mg, vonoprazan 20 mg, or lansoprazole 15 mg for 24 weeks in the maintenance phase.

For healing by week 8, vonoprazan was noninferior to lansoprazole in the primary analysis and superior to lansoprazole in a predefined exploratory analysis (92.9% vs. 84.6%; P < .0001).

Secondary analyses showed that vonoprazan was noninferior to lansoprazole in mean 24-hour heartburn-free days and superior in healing at week 2 for grade C/D esophagitis (70.2% vs. 52.6%; P = .0008).

For maintenance of healing at week 24, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on secondary analysis of healing (80.7% for vonoprazan 20 mg and 79.2% for vonoprazan 10 mg vs. 72.0% for lansoprazole; P < .0001 for both comparisons).

The most common adverse event reported in the healing phase was diarrhea and in the maintenance phase was COVID-19. Two deaths occurred, both from COVID-19, during the maintenance phase in the vonoprazan 20-mg group.

As expected, serum gastrin increased to a greater extent with vonoprazan than lansoprazole, with levels > 500 pg/mL in 16% of those taking 20 mg at the end of maintenance therapy, the authors report. After stopping vonoprazan, gastrin levels dropped by roughly 60%-65% within 4 weeks.
 

Promising new option

“PCABs are a promising new option,” Avin Aggarwal, MD, who was not involved in the study, told this news organization.

They have a “more potent acid inhibitory effect” and have shown “superior healing of erosive esophagitis,” said Dr. Aggarwal, a gastroenterologist and medical director of Banner Health’s South Campus endoscopy services and clinical assistant professor at the University of Arizona in Tucson.

The results of the PHALCON-EE trial “validate noninferiority of PCABs compared to standard PPI therapy in the Western population after being proven in multiple Asian studies,” he said.

Dr. Aggarwal noted that PCABs work the same way as PPIs, by blocking the proton pumps, but “the longer half-life of PCABs and action on both active and inactive proton channels result in greater acid inhibition.”

Long-term effects of PCAB therapy from stronger acid inhibition and resulting hypergastrinemia still remain to be determined, he said.

Earlier this year, the U.S. Food and Drug Administration accepted Phathom Pharmaceuticals’ new drug application for vonoprazan for the treatment of erosive esophagitis.

Last May, the FDA approved two vonoprazan-based therapies for the treatment of H. pylori infection.

The study was funded by Phathom Pharmaceuticals. Dr. Laine and several coauthors have disclosed financial relationships with the company. Dr. Aggarwal reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The oral potassium-competitive acid blocker (PCAB) vonoprazan was noninferior and superior to the proton-pump inhibitor (PPI) lansoprazole for erosive esophagitis, according to results of the phase 3 PHALCON-EE trial.

Vonoprazan achieved higher rates of healing and maintenance of healing than lansoprazole, with the benefit seen primarily in patients with more severe esophagitis.

The differences in healing rates were evident after 2 weeks of therapy and were maintained throughout the 24-week study, report Loren Laine, MD, Yale University, New Haven, Conn., and colleagues.

The study was published online in Gastroenterology.
 

More potent acid suppression

Gastroesophageal reflux disease is one of the most common disorders of the gastrointestinal tract, and erosive esophagitis is its most common complication.

Although standard PPI therapy is effective for healing erosive esophagitis, some patients do not achieve success with this conventional treatment.

Studies suggest that lack of healing of erosive esophagitis with 8 weeks of PPI therapy can be expected in roughly 5%-20% of patients, with rates up to 30% reported in patients with more severe esophagitis.

The PCAB vonoprazan provides more potent inhibition of gastric acid than PPIs and is seen as a potential alternative. However, data on its efficacy for erosive esophagitis are limited, the authors note.

The PHALCON-EE trial enrolled 1,024 adults from the United States and Europe with erosive esophagitis without Helicobacter pylori infection or Barrett esophagus.

Participants were randomized to receive once-daily vonoprazan 20 mg or lansoprazole 30 mg for up to 8 weeks in the healing phase.

The 878 patients with healing were then rerandomized to receive once-daily vonoprazan 10 mg, vonoprazan 20 mg, or lansoprazole 15 mg for 24 weeks in the maintenance phase.

For healing by week 8, vonoprazan was noninferior to lansoprazole in the primary analysis and superior to lansoprazole in a predefined exploratory analysis (92.9% vs. 84.6%; P < .0001).

Secondary analyses showed that vonoprazan was noninferior to lansoprazole in mean 24-hour heartburn-free days and superior in healing at week 2 for grade C/D esophagitis (70.2% vs. 52.6%; P = .0008).

For maintenance of healing at week 24, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on secondary analysis of healing (80.7% for vonoprazan 20 mg and 79.2% for vonoprazan 10 mg vs. 72.0% for lansoprazole; P < .0001 for both comparisons).

The most common adverse event reported in the healing phase was diarrhea and in the maintenance phase was COVID-19. Two deaths occurred, both from COVID-19, during the maintenance phase in the vonoprazan 20-mg group.

As expected, serum gastrin increased to a greater extent with vonoprazan than lansoprazole, with levels > 500 pg/mL in 16% of those taking 20 mg at the end of maintenance therapy, the authors report. After stopping vonoprazan, gastrin levels dropped by roughly 60%-65% within 4 weeks.
 

Promising new option

“PCABs are a promising new option,” Avin Aggarwal, MD, who was not involved in the study, told this news organization.

They have a “more potent acid inhibitory effect” and have shown “superior healing of erosive esophagitis,” said Dr. Aggarwal, a gastroenterologist and medical director of Banner Health’s South Campus endoscopy services and clinical assistant professor at the University of Arizona in Tucson.

The results of the PHALCON-EE trial “validate noninferiority of PCABs compared to standard PPI therapy in the Western population after being proven in multiple Asian studies,” he said.

Dr. Aggarwal noted that PCABs work the same way as PPIs, by blocking the proton pumps, but “the longer half-life of PCABs and action on both active and inactive proton channels result in greater acid inhibition.”

Long-term effects of PCAB therapy from stronger acid inhibition and resulting hypergastrinemia still remain to be determined, he said.

Earlier this year, the U.S. Food and Drug Administration accepted Phathom Pharmaceuticals’ new drug application for vonoprazan for the treatment of erosive esophagitis.

Last May, the FDA approved two vonoprazan-based therapies for the treatment of H. pylori infection.

The study was funded by Phathom Pharmaceuticals. Dr. Laine and several coauthors have disclosed financial relationships with the company. Dr. Aggarwal reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The oral potassium-competitive acid blocker (PCAB) vonoprazan was noninferior and superior to the proton-pump inhibitor (PPI) lansoprazole for erosive esophagitis, according to results of the phase 3 PHALCON-EE trial.

Vonoprazan achieved higher rates of healing and maintenance of healing than lansoprazole, with the benefit seen primarily in patients with more severe esophagitis.

The differences in healing rates were evident after 2 weeks of therapy and were maintained throughout the 24-week study, report Loren Laine, MD, Yale University, New Haven, Conn., and colleagues.

The study was published online in Gastroenterology.
 

More potent acid suppression

Gastroesophageal reflux disease is one of the most common disorders of the gastrointestinal tract, and erosive esophagitis is its most common complication.

Although standard PPI therapy is effective for healing erosive esophagitis, some patients do not achieve success with this conventional treatment.

Studies suggest that lack of healing of erosive esophagitis with 8 weeks of PPI therapy can be expected in roughly 5%-20% of patients, with rates up to 30% reported in patients with more severe esophagitis.

The PCAB vonoprazan provides more potent inhibition of gastric acid than PPIs and is seen as a potential alternative. However, data on its efficacy for erosive esophagitis are limited, the authors note.

The PHALCON-EE trial enrolled 1,024 adults from the United States and Europe with erosive esophagitis without Helicobacter pylori infection or Barrett esophagus.

Participants were randomized to receive once-daily vonoprazan 20 mg or lansoprazole 30 mg for up to 8 weeks in the healing phase.

The 878 patients with healing were then rerandomized to receive once-daily vonoprazan 10 mg, vonoprazan 20 mg, or lansoprazole 15 mg for 24 weeks in the maintenance phase.

For healing by week 8, vonoprazan was noninferior to lansoprazole in the primary analysis and superior to lansoprazole in a predefined exploratory analysis (92.9% vs. 84.6%; P < .0001).

Secondary analyses showed that vonoprazan was noninferior to lansoprazole in mean 24-hour heartburn-free days and superior in healing at week 2 for grade C/D esophagitis (70.2% vs. 52.6%; P = .0008).

For maintenance of healing at week 24, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on secondary analysis of healing (80.7% for vonoprazan 20 mg and 79.2% for vonoprazan 10 mg vs. 72.0% for lansoprazole; P < .0001 for both comparisons).

The most common adverse event reported in the healing phase was diarrhea and in the maintenance phase was COVID-19. Two deaths occurred, both from COVID-19, during the maintenance phase in the vonoprazan 20-mg group.

As expected, serum gastrin increased to a greater extent with vonoprazan than lansoprazole, with levels > 500 pg/mL in 16% of those taking 20 mg at the end of maintenance therapy, the authors report. After stopping vonoprazan, gastrin levels dropped by roughly 60%-65% within 4 weeks.
 

Promising new option

“PCABs are a promising new option,” Avin Aggarwal, MD, who was not involved in the study, told this news organization.

They have a “more potent acid inhibitory effect” and have shown “superior healing of erosive esophagitis,” said Dr. Aggarwal, a gastroenterologist and medical director of Banner Health’s South Campus endoscopy services and clinical assistant professor at the University of Arizona in Tucson.

The results of the PHALCON-EE trial “validate noninferiority of PCABs compared to standard PPI therapy in the Western population after being proven in multiple Asian studies,” he said.

Dr. Aggarwal noted that PCABs work the same way as PPIs, by blocking the proton pumps, but “the longer half-life of PCABs and action on both active and inactive proton channels result in greater acid inhibition.”

Long-term effects of PCAB therapy from stronger acid inhibition and resulting hypergastrinemia still remain to be determined, he said.

Earlier this year, the U.S. Food and Drug Administration accepted Phathom Pharmaceuticals’ new drug application for vonoprazan for the treatment of erosive esophagitis.

Last May, the FDA approved two vonoprazan-based therapies for the treatment of H. pylori infection.

The study was funded by Phathom Pharmaceuticals. Dr. Laine and several coauthors have disclosed financial relationships with the company. Dr. Aggarwal reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Mailing invitations for hepatocellular carcinoma (HCC) surveillance screening to patients with cirrhosis increased ultrasound uptake by 13 percentage points, but the majority of patients still did not receive the recommended semiannual screenings, according to findings published in Clinical Gastroenterology and Hepatology.

“These data highlight the need for more intensive interventions to further increase surveillance,” wrote Amit Singal, MD, of University of Texas Southwestern Medical Center and Parkland Health Hospital System in Dallas, and colleagues. “The underuse of HCC surveillance has been attributed to a combination of patient- and provider-level barriers, which can serve as future additional intervention targets.” These include transportation and financial barriers and possibly new blood-based screening modalities when they become available, thereby removing the need for a separate ultrasound appointment.

According to one study, more than 90% of hepatocellular carcinoma cases occur in people with chronic liver disease, and the cancer is a leading cause of death in those with compensated cirrhosis. Multiple medical associations therefore recommend an abdominal ultrasound every 6 months with or without alpha-fetoprotein (AFP) for surveillance in at-risk patients, including anyone with cirrhosis of any kind, but too few patients receive these surveillance ultrasounds, the authors write.

The researchers therefore conducted a pragmatic randomized clinical trial from March 2018 to September 2019 to compare surveillance ultrasound uptake for two groups of people with cirrhosis: 1,436 people who were mailed invitations to get a surveillance ultrasound and 1,436 people who received usual care, with surveillance recommended only at usual visits. The patients all received care at one of three health systems: a tertiary care referral center, a safety net health system, and a Veterans Affairs medical center. The primary outcome was semiannual surveillance in the patients over 1 year.

The researchers identified patients using ICD-9 and ICD-10 codes for cirrhosis and cirrhosis complications, as well as those with suspected but undocumented cirrhosis based on electronic medical record notes such as an elevated Fibrosis-4 index. They confirmed the diagnoses with chart review, confirmed that the patients had at least one outpatient visit in the previous year, and excluded those in whom surveillance is not recommended, who lacked contact information, or who spoke a language besides English or Spanish.

The mailing was a one-page letter in English and Spanish, written at a low literacy level, that explained hepatocellular carcinoma risk and recommended surveillance. Those who didn’t respond to the mailed invitation within 2 weeks received a reminder call to undergo surveillance, and those who scheduled an ultrasound received a reminder call about a week before the visit. Primary and subspecialty providers were blinded to the patients’ study arm assignments.

“We conducted the study as a pragmatic trial whereby patients in either arm could also be offered HCC surveillance by primary or specialty care providers during clinic visits,” the researchers wrote. “The frequency of the clinic visits and provider discussions regarding HCC surveillance were conducted per usual care and not dictated by the study protocol.”

Two-thirds of the patients (67.7%) were men, with a median age of 61.2 years. Just over a third (37.0%) were white, 31.9% were Hispanic, and 27.6% were Black. More than half the patients had hepatitis C (56.4%), 18.1% had alcohol-related liver disease, 14.5% had nonalcoholic fatty liver disease, and 2.4% had hepatitis B. Most of the patients had compensated cirrhosis, including 36.7% with ascites and 17.1% with hepatic encephalopathy.

Nearly a quarter of the patients in the outreach arm (23%) could not be contacted or lacked working phone numbers, but they remained in the intent-to-screen analysis. Just over a third of the patients who received mailed outreach (35.1%; 95% confidence interval, 32.6%-37.6%) received semiannual surveillance, compared to 21.9% (95% CI, 19.8%-24.2%) of the usual-care patients. The increased surveillance in the outreach group applied to most subgroups, including race/ethnicity and cirrhosis severity based on the Child-Turcotte-Pugh class.

“However, we observed site-level differences in the intervention effect, with significant increases in semiannual surveillance at the VA and safety net health systems (both P < .001) but not at the tertiary care referral center (P = .52),” the authors wrote. “In a post hoc subgroup analysis among patients with at least 1 primary care or gastroenterology outpatient visit during the study period, mailed outreach continued to increase semiannual surveillance, compared with usual care (46.8% vs. 32.7%; P < .001).”

Despite the improved rates from the intervention, the majority of patients still did not receive semiannual surveillance across all three sites, and almost 30% underwent no surveillance the entire year.

The research was funded by the National Cancer Institute, the Cancer Prevention Research Institute of Texas, and the Center for Innovations in Quality, Effectiveness and Safety. Dr. Singal has consulted for or served on the advisory boards of Bayer, FujiFilm Medical Sciences, Exact Sciences, Roche, Glycotest, and GRAIL. The other authors had no industry disclosures.

Mailing invitations for hepatocellular carcinoma (HCC) surveillance screening to patients with cirrhosis increased ultrasound uptake by 13 percentage points, but the majority of patients still did not receive the recommended semiannual screenings, according to findings published in Clinical Gastroenterology and Hepatology.

“These data highlight the need for more intensive interventions to further increase surveillance,” wrote Amit Singal, MD, of University of Texas Southwestern Medical Center and Parkland Health Hospital System in Dallas, and colleagues. “The underuse of HCC surveillance has been attributed to a combination of patient- and provider-level barriers, which can serve as future additional intervention targets.” These include transportation and financial barriers and possibly new blood-based screening modalities when they become available, thereby removing the need for a separate ultrasound appointment.

According to one study, more than 90% of hepatocellular carcinoma cases occur in people with chronic liver disease, and the cancer is a leading cause of death in those with compensated cirrhosis. Multiple medical associations therefore recommend an abdominal ultrasound every 6 months with or without alpha-fetoprotein (AFP) for surveillance in at-risk patients, including anyone with cirrhosis of any kind, but too few patients receive these surveillance ultrasounds, the authors write.

The researchers therefore conducted a pragmatic randomized clinical trial from March 2018 to September 2019 to compare surveillance ultrasound uptake for two groups of people with cirrhosis: 1,436 people who were mailed invitations to get a surveillance ultrasound and 1,436 people who received usual care, with surveillance recommended only at usual visits. The patients all received care at one of three health systems: a tertiary care referral center, a safety net health system, and a Veterans Affairs medical center. The primary outcome was semiannual surveillance in the patients over 1 year.

The researchers identified patients using ICD-9 and ICD-10 codes for cirrhosis and cirrhosis complications, as well as those with suspected but undocumented cirrhosis based on electronic medical record notes such as an elevated Fibrosis-4 index. They confirmed the diagnoses with chart review, confirmed that the patients had at least one outpatient visit in the previous year, and excluded those in whom surveillance is not recommended, who lacked contact information, or who spoke a language besides English or Spanish.

The mailing was a one-page letter in English and Spanish, written at a low literacy level, that explained hepatocellular carcinoma risk and recommended surveillance. Those who didn’t respond to the mailed invitation within 2 weeks received a reminder call to undergo surveillance, and those who scheduled an ultrasound received a reminder call about a week before the visit. Primary and subspecialty providers were blinded to the patients’ study arm assignments.

“We conducted the study as a pragmatic trial whereby patients in either arm could also be offered HCC surveillance by primary or specialty care providers during clinic visits,” the researchers wrote. “The frequency of the clinic visits and provider discussions regarding HCC surveillance were conducted per usual care and not dictated by the study protocol.”

Two-thirds of the patients (67.7%) were men, with a median age of 61.2 years. Just over a third (37.0%) were white, 31.9% were Hispanic, and 27.6% were Black. More than half the patients had hepatitis C (56.4%), 18.1% had alcohol-related liver disease, 14.5% had nonalcoholic fatty liver disease, and 2.4% had hepatitis B. Most of the patients had compensated cirrhosis, including 36.7% with ascites and 17.1% with hepatic encephalopathy.

Nearly a quarter of the patients in the outreach arm (23%) could not be contacted or lacked working phone numbers, but they remained in the intent-to-screen analysis. Just over a third of the patients who received mailed outreach (35.1%; 95% confidence interval, 32.6%-37.6%) received semiannual surveillance, compared to 21.9% (95% CI, 19.8%-24.2%) of the usual-care patients. The increased surveillance in the outreach group applied to most subgroups, including race/ethnicity and cirrhosis severity based on the Child-Turcotte-Pugh class.

“However, we observed site-level differences in the intervention effect, with significant increases in semiannual surveillance at the VA and safety net health systems (both P < .001) but not at the tertiary care referral center (P = .52),” the authors wrote. “In a post hoc subgroup analysis among patients with at least 1 primary care or gastroenterology outpatient visit during the study period, mailed outreach continued to increase semiannual surveillance, compared with usual care (46.8% vs. 32.7%; P < .001).”

Despite the improved rates from the intervention, the majority of patients still did not receive semiannual surveillance across all three sites, and almost 30% underwent no surveillance the entire year.

The research was funded by the National Cancer Institute, the Cancer Prevention Research Institute of Texas, and the Center for Innovations in Quality, Effectiveness and Safety. Dr. Singal has consulted for or served on the advisory boards of Bayer, FujiFilm Medical Sciences, Exact Sciences, Roche, Glycotest, and GRAIL. The other authors had no industry disclosures.

Mailing invitations for hepatocellular carcinoma (HCC) surveillance screening to patients with cirrhosis increased ultrasound uptake by 13 percentage points, but the majority of patients still did not receive the recommended semiannual screenings, according to findings published in Clinical Gastroenterology and Hepatology.

“These data highlight the need for more intensive interventions to further increase surveillance,” wrote Amit Singal, MD, of University of Texas Southwestern Medical Center and Parkland Health Hospital System in Dallas, and colleagues. “The underuse of HCC surveillance has been attributed to a combination of patient- and provider-level barriers, which can serve as future additional intervention targets.” These include transportation and financial barriers and possibly new blood-based screening modalities when they become available, thereby removing the need for a separate ultrasound appointment.

According to one study, more than 90% of hepatocellular carcinoma cases occur in people with chronic liver disease, and the cancer is a leading cause of death in those with compensated cirrhosis. Multiple medical associations therefore recommend an abdominal ultrasound every 6 months with or without alpha-fetoprotein (AFP) for surveillance in at-risk patients, including anyone with cirrhosis of any kind, but too few patients receive these surveillance ultrasounds, the authors write.

The researchers therefore conducted a pragmatic randomized clinical trial from March 2018 to September 2019 to compare surveillance ultrasound uptake for two groups of people with cirrhosis: 1,436 people who were mailed invitations to get a surveillance ultrasound and 1,436 people who received usual care, with surveillance recommended only at usual visits. The patients all received care at one of three health systems: a tertiary care referral center, a safety net health system, and a Veterans Affairs medical center. The primary outcome was semiannual surveillance in the patients over 1 year.

The researchers identified patients using ICD-9 and ICD-10 codes for cirrhosis and cirrhosis complications, as well as those with suspected but undocumented cirrhosis based on electronic medical record notes such as an elevated Fibrosis-4 index. They confirmed the diagnoses with chart review, confirmed that the patients had at least one outpatient visit in the previous year, and excluded those in whom surveillance is not recommended, who lacked contact information, or who spoke a language besides English or Spanish.

The mailing was a one-page letter in English and Spanish, written at a low literacy level, that explained hepatocellular carcinoma risk and recommended surveillance. Those who didn’t respond to the mailed invitation within 2 weeks received a reminder call to undergo surveillance, and those who scheduled an ultrasound received a reminder call about a week before the visit. Primary and subspecialty providers were blinded to the patients’ study arm assignments.

“We conducted the study as a pragmatic trial whereby patients in either arm could also be offered HCC surveillance by primary or specialty care providers during clinic visits,” the researchers wrote. “The frequency of the clinic visits and provider discussions regarding HCC surveillance were conducted per usual care and not dictated by the study protocol.”

Two-thirds of the patients (67.7%) were men, with a median age of 61.2 years. Just over a third (37.0%) were white, 31.9% were Hispanic, and 27.6% were Black. More than half the patients had hepatitis C (56.4%), 18.1% had alcohol-related liver disease, 14.5% had nonalcoholic fatty liver disease, and 2.4% had hepatitis B. Most of the patients had compensated cirrhosis, including 36.7% with ascites and 17.1% with hepatic encephalopathy.

Nearly a quarter of the patients in the outreach arm (23%) could not be contacted or lacked working phone numbers, but they remained in the intent-to-screen analysis. Just over a third of the patients who received mailed outreach (35.1%; 95% confidence interval, 32.6%-37.6%) received semiannual surveillance, compared to 21.9% (95% CI, 19.8%-24.2%) of the usual-care patients. The increased surveillance in the outreach group applied to most subgroups, including race/ethnicity and cirrhosis severity based on the Child-Turcotte-Pugh class.

“However, we observed site-level differences in the intervention effect, with significant increases in semiannual surveillance at the VA and safety net health systems (both P < .001) but not at the tertiary care referral center (P = .52),” the authors wrote. “In a post hoc subgroup analysis among patients with at least 1 primary care or gastroenterology outpatient visit during the study period, mailed outreach continued to increase semiannual surveillance, compared with usual care (46.8% vs. 32.7%; P < .001).”

Despite the improved rates from the intervention, the majority of patients still did not receive semiannual surveillance across all three sites, and almost 30% underwent no surveillance the entire year.

The research was funded by the National Cancer Institute, the Cancer Prevention Research Institute of Texas, and the Center for Innovations in Quality, Effectiveness and Safety. Dr. Singal has consulted for or served on the advisory boards of Bayer, FujiFilm Medical Sciences, Exact Sciences, Roche, Glycotest, and GRAIL. The other authors had no industry disclosures.

Interleukin-22 may mitigate nonalcoholic fatty liver disease (NAFLD)–related fibrosis in females but not males, suggesting a sex-linked hepatoprotective pathway, according to investigators.

These differences between men and women should be considered when conducting clinical trials for IL-22–targeting therapies, reported lead author Mohamed N. Abdelnabi, MSc, of the Centre de Recherche du Centre Hospitalier de l’Université de Montréal and colleagues.

“IL-22 is a pleiotropic cytokine with both inflammatory and protective effects during injury and repair in various tissues including the liver,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, noting that IL-22 activity has been linked with both antifibrotic and profibrotic outcomes in previous preclinical studies. “These different observations highlight the dual nature of IL-22 that likely is dictated by multiple factors including the tissue involved, pathologic environment, endogenous vs. exogenous IL-22 level, and the time of exposure.”

Prior research has left some questions unanswered, the investigators noted, because many studies have relied on exogenous administration of IL-22 in mouse models, some of which lack all the metabolic abnormalities observed in human disease. Furthermore, these mice were all male, which has prevented detection of possible sex-linked differences in IL-22–related pathophysiology, they added.

To address these gaps, the investigators conducted a series of experiments involving men and women with NAFLD, plus mice of both sexes with NAFLD induced by a high-fat diet, both wild-type and with knock-out of the IL-22 receptor.
 

Human data

To characterize IL-22 activity in men versus women with NAFLD, the investigators first analyzed two publicly available microarray datasets. These revealed notably increased expression of hepatic IL-22 mRNA in the livers of females compared with males. Supporting this finding, liver biopsies from 11 men and 9 women with NAFLD with similar levels of fibrosis showed significantly increased IL-22–producing cells in female patients compared with male patients.

“These results suggest a sexual dimorphic expression of IL-22 in the context of NAFLD,” the investigators wrote.
 

Mouse data

Echoing the human data, the livers of female wild-type mice with NAFLD had significantly greater IL-22 expression than male mice at both mRNA and protein levels.

Next, the investigators explored the effects of IL-22–receptor knockout. In addition to NAFLD, these knockout mice developed weight gain and metabolic alterations, especially insulin resistance, supporting previous work that highlighted the protective role of IL-22 against these outcomes. More relevant to the present study, female knockout mice had significantly worse hepatic liver injury, apoptosis, inflammation, and fibrosis than male knockout mice, suggesting that IL-22 signaling confers hepatoprotection in females but not males.

“These observations may suggest a regulation of IL-22 expression by the female sex hormone estrogen,” the investigators wrote. “Indeed, estrogen is known to modulate inflammatory responses in NAFLD, but the underlying mechanisms remain undefined. ... Further in vivo studies are warranted to investigate whether endogenous estrogen regulates hepatic IL-22 expression in the context of NAFLD.”

In the meantime, the present data may steer drug development.

“These findings should be considered in clinical trials testing IL-22–based therapeutic approaches in treatment of female vs. male subjects with NAFLD,” the investigators concluded.

The study was partially funded by the Canadian Liver Foundation and the Canadian Institutes of Health Research, the Bourse d’Exemption des Droits de Scolarité Supplémentaires from the Université de Montréal, the Canadian Network on Hepatitis, and others. The investigators disclosed no competing interests.

Interleukin-22 may mitigate nonalcoholic fatty liver disease (NAFLD)–related fibrosis in females but not males, suggesting a sex-linked hepatoprotective pathway, according to investigators.

These differences between men and women should be considered when conducting clinical trials for IL-22–targeting therapies, reported lead author Mohamed N. Abdelnabi, MSc, of the Centre de Recherche du Centre Hospitalier de l’Université de Montréal and colleagues.

“IL-22 is a pleiotropic cytokine with both inflammatory and protective effects during injury and repair in various tissues including the liver,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, noting that IL-22 activity has been linked with both antifibrotic and profibrotic outcomes in previous preclinical studies. “These different observations highlight the dual nature of IL-22 that likely is dictated by multiple factors including the tissue involved, pathologic environment, endogenous vs. exogenous IL-22 level, and the time of exposure.”

Prior research has left some questions unanswered, the investigators noted, because many studies have relied on exogenous administration of IL-22 in mouse models, some of which lack all the metabolic abnormalities observed in human disease. Furthermore, these mice were all male, which has prevented detection of possible sex-linked differences in IL-22–related pathophysiology, they added.

To address these gaps, the investigators conducted a series of experiments involving men and women with NAFLD, plus mice of both sexes with NAFLD induced by a high-fat diet, both wild-type and with knock-out of the IL-22 receptor.
 

Human data

To characterize IL-22 activity in men versus women with NAFLD, the investigators first analyzed two publicly available microarray datasets. These revealed notably increased expression of hepatic IL-22 mRNA in the livers of females compared with males. Supporting this finding, liver biopsies from 11 men and 9 women with NAFLD with similar levels of fibrosis showed significantly increased IL-22–producing cells in female patients compared with male patients.

“These results suggest a sexual dimorphic expression of IL-22 in the context of NAFLD,” the investigators wrote.
 

Mouse data

Echoing the human data, the livers of female wild-type mice with NAFLD had significantly greater IL-22 expression than male mice at both mRNA and protein levels.

Next, the investigators explored the effects of IL-22–receptor knockout. In addition to NAFLD, these knockout mice developed weight gain and metabolic alterations, especially insulin resistance, supporting previous work that highlighted the protective role of IL-22 against these outcomes. More relevant to the present study, female knockout mice had significantly worse hepatic liver injury, apoptosis, inflammation, and fibrosis than male knockout mice, suggesting that IL-22 signaling confers hepatoprotection in females but not males.

“These observations may suggest a regulation of IL-22 expression by the female sex hormone estrogen,” the investigators wrote. “Indeed, estrogen is known to modulate inflammatory responses in NAFLD, but the underlying mechanisms remain undefined. ... Further in vivo studies are warranted to investigate whether endogenous estrogen regulates hepatic IL-22 expression in the context of NAFLD.”

In the meantime, the present data may steer drug development.

“These findings should be considered in clinical trials testing IL-22–based therapeutic approaches in treatment of female vs. male subjects with NAFLD,” the investigators concluded.

The study was partially funded by the Canadian Liver Foundation and the Canadian Institutes of Health Research, the Bourse d’Exemption des Droits de Scolarité Supplémentaires from the Université de Montréal, the Canadian Network on Hepatitis, and others. The investigators disclosed no competing interests.

Interleukin-22 may mitigate nonalcoholic fatty liver disease (NAFLD)–related fibrosis in females but not males, suggesting a sex-linked hepatoprotective pathway, according to investigators.

These differences between men and women should be considered when conducting clinical trials for IL-22–targeting therapies, reported lead author Mohamed N. Abdelnabi, MSc, of the Centre de Recherche du Centre Hospitalier de l’Université de Montréal and colleagues.

“IL-22 is a pleiotropic cytokine with both inflammatory and protective effects during injury and repair in various tissues including the liver,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, noting that IL-22 activity has been linked with both antifibrotic and profibrotic outcomes in previous preclinical studies. “These different observations highlight the dual nature of IL-22 that likely is dictated by multiple factors including the tissue involved, pathologic environment, endogenous vs. exogenous IL-22 level, and the time of exposure.”

Prior research has left some questions unanswered, the investigators noted, because many studies have relied on exogenous administration of IL-22 in mouse models, some of which lack all the metabolic abnormalities observed in human disease. Furthermore, these mice were all male, which has prevented detection of possible sex-linked differences in IL-22–related pathophysiology, they added.

To address these gaps, the investigators conducted a series of experiments involving men and women with NAFLD, plus mice of both sexes with NAFLD induced by a high-fat diet, both wild-type and with knock-out of the IL-22 receptor.
 

Human data

To characterize IL-22 activity in men versus women with NAFLD, the investigators first analyzed two publicly available microarray datasets. These revealed notably increased expression of hepatic IL-22 mRNA in the livers of females compared with males. Supporting this finding, liver biopsies from 11 men and 9 women with NAFLD with similar levels of fibrosis showed significantly increased IL-22–producing cells in female patients compared with male patients.

“These results suggest a sexual dimorphic expression of IL-22 in the context of NAFLD,” the investigators wrote.
 

Mouse data

Echoing the human data, the livers of female wild-type mice with NAFLD had significantly greater IL-22 expression than male mice at both mRNA and protein levels.

Next, the investigators explored the effects of IL-22–receptor knockout. In addition to NAFLD, these knockout mice developed weight gain and metabolic alterations, especially insulin resistance, supporting previous work that highlighted the protective role of IL-22 against these outcomes. More relevant to the present study, female knockout mice had significantly worse hepatic liver injury, apoptosis, inflammation, and fibrosis than male knockout mice, suggesting that IL-22 signaling confers hepatoprotection in females but not males.

“These observations may suggest a regulation of IL-22 expression by the female sex hormone estrogen,” the investigators wrote. “Indeed, estrogen is known to modulate inflammatory responses in NAFLD, but the underlying mechanisms remain undefined. ... Further in vivo studies are warranted to investigate whether endogenous estrogen regulates hepatic IL-22 expression in the context of NAFLD.”

In the meantime, the present data may steer drug development.

“These findings should be considered in clinical trials testing IL-22–based therapeutic approaches in treatment of female vs. male subjects with NAFLD,” the investigators concluded.

The study was partially funded by the Canadian Liver Foundation and the Canadian Institutes of Health Research, the Bourse d’Exemption des Droits de Scolarité Supplémentaires from the Université de Montréal, the Canadian Network on Hepatitis, and others. The investigators disclosed no competing interests.

A real-world analysis confirms that fecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection (rCDI) – and there is no difference between delivery by capsule (cap-FMT) and colonoscopy (colo-FMT).

“We present one of the largest cohorts involving people who received capsule FMT. The finding that capsule FMT is as safe and effective as colonoscopy FMT has practical implications for anyone suffering with rCDI today,” Byron Vaughn, MD, with the division of gastroenterology, hepatology, and nutrition, University of Minnesota, Minneapolis, said in an interview.

The study was published online in Clinical Gastroenterology and Hepatology.

The Food and Drug Administration allows FMT to be used for patients who have failed standard treatment for rCDI under a policy of enforcement discretion.

The past decade has seen an increase in the use of FMT in clinical practice, owing to an increase in cases of rCDI after failure of standard antibiotic therapy.

Unlike antibiotics, which perpetuate and worsen intestinal dysbiosis, FMT restores the diversity and function of host microbiota, effectively breaking the cycle of rCDI, the authors of the study noted. But it’s been unclear whether the efficacy and safety of FMT vary by route of administration.
 

Effective without procedural risks

To investigate, Dr. Vaughn and colleagues evaluated clinical outcomes and adverse events in 170 patients with rCDI who underwent cap-FMT and 96 peers who underwent colo-FMT.

FMT was performed using one of two standardized formulations of microbiota manufactured by the University of Minnesota microbiota therapeutics program: freeze-dried/encapsulated or frozen-thawed/liquid.

Overall, the cure rates of CDI were 86% at 1 month and 81% at 2 months. There was no statistically significant difference at either time between cap-FMT and colo-FMT.

The 1-month cure rate was 84% with cap-FMT and 91% with colo-FMT; at 2 months, the cure rates were 81% and 83%, respectively.

Cap-FMT has a safety and effectiveness profile similar to that of colo-FMT, without the procedural risks of colonoscopy, the researchers concluded.

They cautioned that, although FMT is highly effective overall, patient selection is a key factor to optimizing FMT success.

Older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression.

“These risk factors can help determine if a patient should receive FMT or an alternative therapy for rCDI. This is not to say FMT should be avoided in older patients or those on dialysis, but clinicians should be aware of these associations in light of other options for rCDI,” Dr. Vaughn said.

Confirming prior studies, antibiotic use after FMT was a major factor in its failure. Patient selection for FMT should include an assessment of the potential need for antibiotics after transplant, the researchers noted.

One serious adverse event (aspiration pneumonia) was related to colonoscopy; otherwise, no new safety signals were identified.

As reported in other studies, changes in bowel function, including diarrhea, constipation, gas, and bloating were common, although it’s tough to disentangle gastrointestinal symptoms related to FMT from those after CDI, the researchers said. Importantly, no transmission of an infectious agent related to FMT was identified.
 

Two good options

The researchers said their findings are “highly generalizable” because the population reflects all FMT use by participating institutions and contains a mix of academic centers and private practices.

Many patients included in the study would not have been eligible for a clinical trial, owing to their having many comorbid conditions, including immune compromise and inflammatory bowel disease, the authors noted.

“FMT is recommended by major gastroenterology and infectious disease society guidelines,” Dr. Vaughn said. “Our group, and others, have consistently found strategies that incorporate FMT as cost-effective strategies for treating rCDI.”

However, lack of access to FMT products often is a barrier to treatment, he said.

“A stool banking model, similar to the nonprofit blood banking model, may be a useful solution to ensure equitable access to FMT to all who need it,” Dr. Vaughn added.

Reached for comment, Majdi Osman, MD, MPH, told this news organization that the study is valuable, “as it nicely shows in a real-world setting that capsules and colonoscopy are good options for patients who need this.”

Dr. Osman is chief medical officer of OpenBiome, a nonprofit organization that operates a public stool bank and is the major FMT source in the United States. The organization has provided over 63,000 FMT treatments to over 1,200 hospitals in the United States.

“FMT has become standard of care for patients who failed antibiotic therapy, and certainly is being used widely as a treatment option for these patients who have often run out of existing options,” Dr. Osman said.

Support for the study was provided by a donation from Achieving Cures Together, a nonprofit organization dedicated to advancing microbiome-based research. Dr. Vaughn receives grant support from Takeda, Roche, Celgene, and Diasorin and has received consulting fees from Prometheus and AbbVie. Dr. Osman reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A real-world analysis confirms that fecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection (rCDI) – and there is no difference between delivery by capsule (cap-FMT) and colonoscopy (colo-FMT).

“We present one of the largest cohorts involving people who received capsule FMT. The finding that capsule FMT is as safe and effective as colonoscopy FMT has practical implications for anyone suffering with rCDI today,” Byron Vaughn, MD, with the division of gastroenterology, hepatology, and nutrition, University of Minnesota, Minneapolis, said in an interview.

The study was published online in Clinical Gastroenterology and Hepatology.

The Food and Drug Administration allows FMT to be used for patients who have failed standard treatment for rCDI under a policy of enforcement discretion.

The past decade has seen an increase in the use of FMT in clinical practice, owing to an increase in cases of rCDI after failure of standard antibiotic therapy.

Unlike antibiotics, which perpetuate and worsen intestinal dysbiosis, FMT restores the diversity and function of host microbiota, effectively breaking the cycle of rCDI, the authors of the study noted. But it’s been unclear whether the efficacy and safety of FMT vary by route of administration.
 

Effective without procedural risks

To investigate, Dr. Vaughn and colleagues evaluated clinical outcomes and adverse events in 170 patients with rCDI who underwent cap-FMT and 96 peers who underwent colo-FMT.

FMT was performed using one of two standardized formulations of microbiota manufactured by the University of Minnesota microbiota therapeutics program: freeze-dried/encapsulated or frozen-thawed/liquid.

Overall, the cure rates of CDI were 86% at 1 month and 81% at 2 months. There was no statistically significant difference at either time between cap-FMT and colo-FMT.

The 1-month cure rate was 84% with cap-FMT and 91% with colo-FMT; at 2 months, the cure rates were 81% and 83%, respectively.

Cap-FMT has a safety and effectiveness profile similar to that of colo-FMT, without the procedural risks of colonoscopy, the researchers concluded.

They cautioned that, although FMT is highly effective overall, patient selection is a key factor to optimizing FMT success.

Older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression.

“These risk factors can help determine if a patient should receive FMT or an alternative therapy for rCDI. This is not to say FMT should be avoided in older patients or those on dialysis, but clinicians should be aware of these associations in light of other options for rCDI,” Dr. Vaughn said.

Confirming prior studies, antibiotic use after FMT was a major factor in its failure. Patient selection for FMT should include an assessment of the potential need for antibiotics after transplant, the researchers noted.

One serious adverse event (aspiration pneumonia) was related to colonoscopy; otherwise, no new safety signals were identified.

As reported in other studies, changes in bowel function, including diarrhea, constipation, gas, and bloating were common, although it’s tough to disentangle gastrointestinal symptoms related to FMT from those after CDI, the researchers said. Importantly, no transmission of an infectious agent related to FMT was identified.
 

Two good options

The researchers said their findings are “highly generalizable” because the population reflects all FMT use by participating institutions and contains a mix of academic centers and private practices.

Many patients included in the study would not have been eligible for a clinical trial, owing to their having many comorbid conditions, including immune compromise and inflammatory bowel disease, the authors noted.

“FMT is recommended by major gastroenterology and infectious disease society guidelines,” Dr. Vaughn said. “Our group, and others, have consistently found strategies that incorporate FMT as cost-effective strategies for treating rCDI.”

However, lack of access to FMT products often is a barrier to treatment, he said.

“A stool banking model, similar to the nonprofit blood banking model, may be a useful solution to ensure equitable access to FMT to all who need it,” Dr. Vaughn added.

Reached for comment, Majdi Osman, MD, MPH, told this news organization that the study is valuable, “as it nicely shows in a real-world setting that capsules and colonoscopy are good options for patients who need this.”

Dr. Osman is chief medical officer of OpenBiome, a nonprofit organization that operates a public stool bank and is the major FMT source in the United States. The organization has provided over 63,000 FMT treatments to over 1,200 hospitals in the United States.

“FMT has become standard of care for patients who failed antibiotic therapy, and certainly is being used widely as a treatment option for these patients who have often run out of existing options,” Dr. Osman said.

Support for the study was provided by a donation from Achieving Cures Together, a nonprofit organization dedicated to advancing microbiome-based research. Dr. Vaughn receives grant support from Takeda, Roche, Celgene, and Diasorin and has received consulting fees from Prometheus and AbbVie. Dr. Osman reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A real-world analysis confirms that fecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection (rCDI) – and there is no difference between delivery by capsule (cap-FMT) and colonoscopy (colo-FMT).

“We present one of the largest cohorts involving people who received capsule FMT. The finding that capsule FMT is as safe and effective as colonoscopy FMT has practical implications for anyone suffering with rCDI today,” Byron Vaughn, MD, with the division of gastroenterology, hepatology, and nutrition, University of Minnesota, Minneapolis, said in an interview.

The study was published online in Clinical Gastroenterology and Hepatology.

The Food and Drug Administration allows FMT to be used for patients who have failed standard treatment for rCDI under a policy of enforcement discretion.

The past decade has seen an increase in the use of FMT in clinical practice, owing to an increase in cases of rCDI after failure of standard antibiotic therapy.

Unlike antibiotics, which perpetuate and worsen intestinal dysbiosis, FMT restores the diversity and function of host microbiota, effectively breaking the cycle of rCDI, the authors of the study noted. But it’s been unclear whether the efficacy and safety of FMT vary by route of administration.
 

Effective without procedural risks

To investigate, Dr. Vaughn and colleagues evaluated clinical outcomes and adverse events in 170 patients with rCDI who underwent cap-FMT and 96 peers who underwent colo-FMT.

FMT was performed using one of two standardized formulations of microbiota manufactured by the University of Minnesota microbiota therapeutics program: freeze-dried/encapsulated or frozen-thawed/liquid.

Overall, the cure rates of CDI were 86% at 1 month and 81% at 2 months. There was no statistically significant difference at either time between cap-FMT and colo-FMT.

The 1-month cure rate was 84% with cap-FMT and 91% with colo-FMT; at 2 months, the cure rates were 81% and 83%, respectively.

Cap-FMT has a safety and effectiveness profile similar to that of colo-FMT, without the procedural risks of colonoscopy, the researchers concluded.

They cautioned that, although FMT is highly effective overall, patient selection is a key factor to optimizing FMT success.

Older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression.

“These risk factors can help determine if a patient should receive FMT or an alternative therapy for rCDI. This is not to say FMT should be avoided in older patients or those on dialysis, but clinicians should be aware of these associations in light of other options for rCDI,” Dr. Vaughn said.

Confirming prior studies, antibiotic use after FMT was a major factor in its failure. Patient selection for FMT should include an assessment of the potential need for antibiotics after transplant, the researchers noted.

One serious adverse event (aspiration pneumonia) was related to colonoscopy; otherwise, no new safety signals were identified.

As reported in other studies, changes in bowel function, including diarrhea, constipation, gas, and bloating were common, although it’s tough to disentangle gastrointestinal symptoms related to FMT from those after CDI, the researchers said. Importantly, no transmission of an infectious agent related to FMT was identified.
 

Two good options

The researchers said their findings are “highly generalizable” because the population reflects all FMT use by participating institutions and contains a mix of academic centers and private practices.

Many patients included in the study would not have been eligible for a clinical trial, owing to their having many comorbid conditions, including immune compromise and inflammatory bowel disease, the authors noted.

“FMT is recommended by major gastroenterology and infectious disease society guidelines,” Dr. Vaughn said. “Our group, and others, have consistently found strategies that incorporate FMT as cost-effective strategies for treating rCDI.”

However, lack of access to FMT products often is a barrier to treatment, he said.

“A stool banking model, similar to the nonprofit blood banking model, may be a useful solution to ensure equitable access to FMT to all who need it,” Dr. Vaughn added.

Reached for comment, Majdi Osman, MD, MPH, told this news organization that the study is valuable, “as it nicely shows in a real-world setting that capsules and colonoscopy are good options for patients who need this.”

Dr. Osman is chief medical officer of OpenBiome, a nonprofit organization that operates a public stool bank and is the major FMT source in the United States. The organization has provided over 63,000 FMT treatments to over 1,200 hospitals in the United States.

“FMT has become standard of care for patients who failed antibiotic therapy, and certainly is being used widely as a treatment option for these patients who have often run out of existing options,” Dr. Osman said.

Support for the study was provided by a donation from Achieving Cures Together, a nonprofit organization dedicated to advancing microbiome-based research. Dr. Vaughn receives grant support from Takeda, Roche, Celgene, and Diasorin and has received consulting fees from Prometheus and AbbVie. Dr. Osman reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Four major professional medical societies in the United States have called for urgent action to create a more sustainable model for digestive health care that decreases the environmental impact of gastroenterology practice, according to a new joint strategic plan published simultaneously in Gastroenterology, Gastrointestinal Endoscopy, American Journal of Gastroenterology, and Hepatology.

The plan outlines numerous strategic goals and objectives across clinical care, education, research, and industry to support sustainable practices. With first author Heiko Pohl, MD, a gastroenterologist and hepatologist at the Veterans Affairs Medical Center in White River Junction, Vermont, and professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H., the joint statement includes task force members from the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy.

“It is clear that the evolving climate crisis, with its deleterious effects on planetary ecosystems, also poses harm to the health of humankind,” the authors wrote in Gastroenterology.

“Climate change affects many social and environmental determinants of health, including water and food security, shelter, physical activity, and accessible health care,” they added. These changes influence gastrointestinal practice (for example, increased risk of obesity and fatty liver disease, disruption of the microbiome, compromised gut immune function).

At the same time, health care delivery contributes to climate change and greenhouse gas emissions worldwide, they wrote. As a procedure-intensive specialty, digestive health care adds to the health care carbon footprint through single-use supplies and high levels of waste.

“As is the case for the impact of climate change by and on health care systems, there is a vicious cycle whereby climate change negatively impacts individual digestive health, which accelerates specialized health care activity, which further contributes to the climate crisis,” the authors wrote.

The multisociety task force noted the transition to a more sustainable model will be challenging and require major modification of current habits in practice. However, the long-term effects “will promote health, save cost, and ... correspond with a broader shared vision of planetary health,” they wrote.

The strategic plan covers seven domains: clinical settings, education, research, society efforts, intersociety efforts, industry, and advocacy. Each domain has specific initiatives for 2023 to 2027. Years 1 and 2 are conceived as a period of self-assessment and planning, followed by implementation and assessment during years 3-5.

In the plan, clinical settings would assess the carbon footprint and waste within all areas of practice and identify low-carbon and low-waste alternatives, such as immediate, short-term, and long-term solutions. This involves creating a framework for GI practices to develop sustainability metrics and offer affordable testing and treatment alternatives with a favorable environmental impact.

Through education, the societies would raise awareness and share sustainability practices with health care leadership, practitioners, and patients regarding the interactions among climate change, digestive health, and health care services. This would include discussions about the professional and ethical implications of old and new patterns of shared resource utilization.

The societies also support raising and allocating resources for research related to the intersections of climate change, digestive health, and health care, with an emphasis on vulnerable groups. This would encourage the inclusion of environmental considerations in research proposals.

At the GI society level, the groups suggest assessing and monitoring the current environmental impact of society-related activities. This entails identifying and implementing measures that would decrease the carbon footprint and reduce waste, as well as track financial costs and savings and environmental benefits from efforts included in a sustainability model.

At the intersociety level, the U.S. groups would collaborate with national and international GI and hepatology societies to support sustainability efforts and use validated metrics to evaluate their efforts. The multisociety plan has received endorsements from nearly two-dozen groups, including the Crohn’s & Colitis Foundation, World Endoscopy Organization, and World Gastroenterology Organisation.

The plan calls for engagement with GI- and hepatology-focused industry and pharmaceutical partners to develop environmentally friendly products, publish information on carbon footprint implications, and promote options for recycling.

Through advocacy efforts, the societies would also identify and incorporate principles of sustainable health care among the goals of relevant political action committees, as well as leverage collaborative advocacy efforts with national and international health care and research agencies, political leaders, and payors.

“We are grateful that several other GI organizations have endorsed our plan, which reflects the importance and timeliness of the opportunity to work together and share best practices to overcome the burden of climate change on digestive health and help mitigate the environmental impact of GI practice,” the authors concluded.

The authors did not declare a funding source for the report. Several of the authors declared financial relationships with pharmaceutical companies, serving as a consultant or receiving research funding.

Four major professional medical societies in the United States have called for urgent action to create a more sustainable model for digestive health care that decreases the environmental impact of gastroenterology practice, according to a new joint strategic plan published simultaneously in Gastroenterology, Gastrointestinal Endoscopy, American Journal of Gastroenterology, and Hepatology.

The plan outlines numerous strategic goals and objectives across clinical care, education, research, and industry to support sustainable practices. With first author Heiko Pohl, MD, a gastroenterologist and hepatologist at the Veterans Affairs Medical Center in White River Junction, Vermont, and professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H., the joint statement includes task force members from the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy.

“It is clear that the evolving climate crisis, with its deleterious effects on planetary ecosystems, also poses harm to the health of humankind,” the authors wrote in Gastroenterology.

“Climate change affects many social and environmental determinants of health, including water and food security, shelter, physical activity, and accessible health care,” they added. These changes influence gastrointestinal practice (for example, increased risk of obesity and fatty liver disease, disruption of the microbiome, compromised gut immune function).

At the same time, health care delivery contributes to climate change and greenhouse gas emissions worldwide, they wrote. As a procedure-intensive specialty, digestive health care adds to the health care carbon footprint through single-use supplies and high levels of waste.

“As is the case for the impact of climate change by and on health care systems, there is a vicious cycle whereby climate change negatively impacts individual digestive health, which accelerates specialized health care activity, which further contributes to the climate crisis,” the authors wrote.

The multisociety task force noted the transition to a more sustainable model will be challenging and require major modification of current habits in practice. However, the long-term effects “will promote health, save cost, and ... correspond with a broader shared vision of planetary health,” they wrote.

The strategic plan covers seven domains: clinical settings, education, research, society efforts, intersociety efforts, industry, and advocacy. Each domain has specific initiatives for 2023 to 2027. Years 1 and 2 are conceived as a period of self-assessment and planning, followed by implementation and assessment during years 3-5.

In the plan, clinical settings would assess the carbon footprint and waste within all areas of practice and identify low-carbon and low-waste alternatives, such as immediate, short-term, and long-term solutions. This involves creating a framework for GI practices to develop sustainability metrics and offer affordable testing and treatment alternatives with a favorable environmental impact.

Through education, the societies would raise awareness and share sustainability practices with health care leadership, practitioners, and patients regarding the interactions among climate change, digestive health, and health care services. This would include discussions about the professional and ethical implications of old and new patterns of shared resource utilization.

The societies also support raising and allocating resources for research related to the intersections of climate change, digestive health, and health care, with an emphasis on vulnerable groups. This would encourage the inclusion of environmental considerations in research proposals.

At the GI society level, the groups suggest assessing and monitoring the current environmental impact of society-related activities. This entails identifying and implementing measures that would decrease the carbon footprint and reduce waste, as well as track financial costs and savings and environmental benefits from efforts included in a sustainability model.

At the intersociety level, the U.S. groups would collaborate with national and international GI and hepatology societies to support sustainability efforts and use validated metrics to evaluate their efforts. The multisociety plan has received endorsements from nearly two-dozen groups, including the Crohn’s & Colitis Foundation, World Endoscopy Organization, and World Gastroenterology Organisation.

The plan calls for engagement with GI- and hepatology-focused industry and pharmaceutical partners to develop environmentally friendly products, publish information on carbon footprint implications, and promote options for recycling.

Through advocacy efforts, the societies would also identify and incorporate principles of sustainable health care among the goals of relevant political action committees, as well as leverage collaborative advocacy efforts with national and international health care and research agencies, political leaders, and payors.

“We are grateful that several other GI organizations have endorsed our plan, which reflects the importance and timeliness of the opportunity to work together and share best practices to overcome the burden of climate change on digestive health and help mitigate the environmental impact of GI practice,” the authors concluded.

The authors did not declare a funding source for the report. Several of the authors declared financial relationships with pharmaceutical companies, serving as a consultant or receiving research funding.

Four major professional medical societies in the United States have called for urgent action to create a more sustainable model for digestive health care that decreases the environmental impact of gastroenterology practice, according to a new joint strategic plan published simultaneously in Gastroenterology, Gastrointestinal Endoscopy, American Journal of Gastroenterology, and Hepatology.

The plan outlines numerous strategic goals and objectives across clinical care, education, research, and industry to support sustainable practices. With first author Heiko Pohl, MD, a gastroenterologist and hepatologist at the Veterans Affairs Medical Center in White River Junction, Vermont, and professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H., the joint statement includes task force members from the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy.

“It is clear that the evolving climate crisis, with its deleterious effects on planetary ecosystems, also poses harm to the health of humankind,” the authors wrote in Gastroenterology.

“Climate change affects many social and environmental determinants of health, including water and food security, shelter, physical activity, and accessible health care,” they added. These changes influence gastrointestinal practice (for example, increased risk of obesity and fatty liver disease, disruption of the microbiome, compromised gut immune function).

At the same time, health care delivery contributes to climate change and greenhouse gas emissions worldwide, they wrote. As a procedure-intensive specialty, digestive health care adds to the health care carbon footprint through single-use supplies and high levels of waste.

“As is the case for the impact of climate change by and on health care systems, there is a vicious cycle whereby climate change negatively impacts individual digestive health, which accelerates specialized health care activity, which further contributes to the climate crisis,” the authors wrote.

The multisociety task force noted the transition to a more sustainable model will be challenging and require major modification of current habits in practice. However, the long-term effects “will promote health, save cost, and ... correspond with a broader shared vision of planetary health,” they wrote.

The strategic plan covers seven domains: clinical settings, education, research, society efforts, intersociety efforts, industry, and advocacy. Each domain has specific initiatives for 2023 to 2027. Years 1 and 2 are conceived as a period of self-assessment and planning, followed by implementation and assessment during years 3-5.

In the plan, clinical settings would assess the carbon footprint and waste within all areas of practice and identify low-carbon and low-waste alternatives, such as immediate, short-term, and long-term solutions. This involves creating a framework for GI practices to develop sustainability metrics and offer affordable testing and treatment alternatives with a favorable environmental impact.

Through education, the societies would raise awareness and share sustainability practices with health care leadership, practitioners, and patients regarding the interactions among climate change, digestive health, and health care services. This would include discussions about the professional and ethical implications of old and new patterns of shared resource utilization.

The societies also support raising and allocating resources for research related to the intersections of climate change, digestive health, and health care, with an emphasis on vulnerable groups. This would encourage the inclusion of environmental considerations in research proposals.

At the GI society level, the groups suggest assessing and monitoring the current environmental impact of society-related activities. This entails identifying and implementing measures that would decrease the carbon footprint and reduce waste, as well as track financial costs and savings and environmental benefits from efforts included in a sustainability model.

At the intersociety level, the U.S. groups would collaborate with national and international GI and hepatology societies to support sustainability efforts and use validated metrics to evaluate their efforts. The multisociety plan has received endorsements from nearly two-dozen groups, including the Crohn’s & Colitis Foundation, World Endoscopy Organization, and World Gastroenterology Organisation.

The plan calls for engagement with GI- and hepatology-focused industry and pharmaceutical partners to develop environmentally friendly products, publish information on carbon footprint implications, and promote options for recycling.

Through advocacy efforts, the societies would also identify and incorporate principles of sustainable health care among the goals of relevant political action committees, as well as leverage collaborative advocacy efforts with national and international health care and research agencies, political leaders, and payors.

“We are grateful that several other GI organizations have endorsed our plan, which reflects the importance and timeliness of the opportunity to work together and share best practices to overcome the burden of climate change on digestive health and help mitigate the environmental impact of GI practice,” the authors concluded.

The authors did not declare a funding source for the report. Several of the authors declared financial relationships with pharmaceutical companies, serving as a consultant or receiving research funding.

In a gluten challenge trial, latiglutenase (IMGX003) reduced symptom severity and mucosal deterioration in patients with celiac disease, according to a new study published in Gastroenterology.

Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.

For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.

“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.

In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”

The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.

The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”

Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.

Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.

The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.

The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.

The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.

“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”

The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.

In a gluten challenge trial, latiglutenase (IMGX003) reduced symptom severity and mucosal deterioration in patients with celiac disease, according to a new study published in Gastroenterology.

Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.

For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.

“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.

In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”

The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.

The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”

Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.

Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.

The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.

The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.

The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.

“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”

The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.

In a gluten challenge trial, latiglutenase (IMGX003) reduced symptom severity and mucosal deterioration in patients with celiac disease, according to a new study published in Gastroenterology.

Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.

For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.

“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.

In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”

The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.

The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”

Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.

Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.

The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.

The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.

The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.

“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”

The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.

Acute kidney injury (AKI) in patients with cirrhosis is potentially preventable, and there are clear steps that can be taken to manage and reverse the condition, concludes a clinical practice update from the American Gastroenterological Association.

AKI occurs in 47% of patients hospitalized with complications of cirrhosis and in approximately 30% of outpatients with cirrhosis, resulting in a total cost in the United States of $4 billion, explained Patrick S. Kamath, MD, division of gastroenterology and hepatology, Mayo Medical School, Rochester, Minn., one of the authors of this update.

Moreover, Dr. Kamath told this news organization, among patients with cirrhosis and AKI, morbidity and mortality is sevenfold higher in comparison to those without cirrhosis, and repeated episodes of AKI increase the risk of progression to chronic kidney disease.

To provide practical advice for the clinical management of patients with cirrhosis and AKI, the authors conducted an expert review of the best available published evidence and gathered expert opinion.

The update was published online in Clinical Gastroenterology and Hepatology.
 

Some key takeaways

Among its 14 best practice statements, it describes three situations indicative of AKI:

• A serum creatinine increase of 0.3 mg/dL or more within 48 hours, or
• A serum creatinine increase of 50% or more from baseline, which is a stable serum creatinine in the past 3 months.
• Reduction in urine output of up to 0.5 mL/kg per hour for more than 6 hours.

The update also emphasizes the importance of an accurate diagnosis, inasmuch as not all cases of AKI are due to hepatorenal syndrome (HRS), for example. It goes on to advise that the specific type of AKI be identified through medical history and physical examination, as well as with blood biochemistry, urine microscopic examination, urine chemistry, selected urinary biomarkers, and renal ultrasound.

Additionally, it underscores the need to identify and treat infections and to closely monitor fluid status.

Nancy S. Reau, MD, Rush Medical College, Chicago, who was not involved in the update, commented to this news organization that fluid status is important when giving albumin replacement therapy because of the increased risk for pulmonary edema.

She also highlighted that this update advises against transjugular intrahepatic portosystemic shunts (TIPSs) as a specific treatment for HRS-AKI, noting that, although the 2022 North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension do not advocate for TIPS for this indication, they also indicated that there was enough evidence to advise against it.

In other key best practice advice statements, the update advises clinicians to hold diuretics and nonselective beta blockers and to discontinue nonsteroidal anti-inflammatory drugs (NSAIDs).
 

‘Timely’ update

Overall, Dr. Reau believes that the update is “timely, especially in light of the recent [U.S.] approval of terlipressin, which will change our treatment options.”

This update also supports the American Association for the Study of Liver Diseases (AASLD) 2021 Practice Guidance guidelines on HRS, she added.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., who was not involved in writing the update, told this news organization that the document is important because of the huge increase in mortality among patients with cirrhosis and AKI.

He commented that there has been much advancement in understanding the condition, with updated nomenclature and novel medical treatments, and that this makes the update timely.

Moreover, the update will help clinicians who are involved in the care of patients with cirrhosis, he added.

Dr. Younossi said the update offers a very clearly stated algorithm for how to identify patients whose condition is easily reversible with volume repletion, in comparison with those patients who require medical treatment or even liver transplantation.

“Those things are important because that pathway gives clinicians an idea of how to do this properly,” he said.

“The key for clinicians is to make sure they understand, in the context of cirrhosis, some of the easy things that they can do to prevent AKI,” he continued. He added that the use of NSAIDs in these patients is “going to be problematic.”

Dr. Kamath has a relationship with Sequana Medical. Other authors’ relevant financial relationships are listed in the original article. Dr. Reau has relationships with Salix and Intercept. Dr. Younossi has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This article was updated 12/12/2022.

Acute kidney injury (AKI) in patients with cirrhosis is potentially preventable, and there are clear steps that can be taken to manage and reverse the condition, concludes a clinical practice update from the American Gastroenterological Association.

AKI occurs in 47% of patients hospitalized with complications of cirrhosis and in approximately 30% of outpatients with cirrhosis, resulting in a total cost in the United States of $4 billion, explained Patrick S. Kamath, MD, division of gastroenterology and hepatology, Mayo Medical School, Rochester, Minn., one of the authors of this update.

Moreover, Dr. Kamath told this news organization, among patients with cirrhosis and AKI, morbidity and mortality is sevenfold higher in comparison to those without cirrhosis, and repeated episodes of AKI increase the risk of progression to chronic kidney disease.

To provide practical advice for the clinical management of patients with cirrhosis and AKI, the authors conducted an expert review of the best available published evidence and gathered expert opinion.

The update was published online in Clinical Gastroenterology and Hepatology.
 

Some key takeaways

Among its 14 best practice statements, it describes three situations indicative of AKI:

• A serum creatinine increase of 0.3 mg/dL or more within 48 hours, or
• A serum creatinine increase of 50% or more from baseline, which is a stable serum creatinine in the past 3 months.
• Reduction in urine output of up to 0.5 mL/kg per hour for more than 6 hours.

The update also emphasizes the importance of an accurate diagnosis, inasmuch as not all cases of AKI are due to hepatorenal syndrome (HRS), for example. It goes on to advise that the specific type of AKI be identified through medical history and physical examination, as well as with blood biochemistry, urine microscopic examination, urine chemistry, selected urinary biomarkers, and renal ultrasound.

Additionally, it underscores the need to identify and treat infections and to closely monitor fluid status.

Nancy S. Reau, MD, Rush Medical College, Chicago, who was not involved in the update, commented to this news organization that fluid status is important when giving albumin replacement therapy because of the increased risk for pulmonary edema.

She also highlighted that this update advises against transjugular intrahepatic portosystemic shunts (TIPSs) as a specific treatment for HRS-AKI, noting that, although the 2022 North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension do not advocate for TIPS for this indication, they also indicated that there was enough evidence to advise against it.

In other key best practice advice statements, the update advises clinicians to hold diuretics and nonselective beta blockers and to discontinue nonsteroidal anti-inflammatory drugs (NSAIDs).
 

‘Timely’ update

Overall, Dr. Reau believes that the update is “timely, especially in light of the recent [U.S.] approval of terlipressin, which will change our treatment options.”

This update also supports the American Association for the Study of Liver Diseases (AASLD) 2021 Practice Guidance guidelines on HRS, she added.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., who was not involved in writing the update, told this news organization that the document is important because of the huge increase in mortality among patients with cirrhosis and AKI.

He commented that there has been much advancement in understanding the condition, with updated nomenclature and novel medical treatments, and that this makes the update timely.

Moreover, the update will help clinicians who are involved in the care of patients with cirrhosis, he added.

Dr. Younossi said the update offers a very clearly stated algorithm for how to identify patients whose condition is easily reversible with volume repletion, in comparison with those patients who require medical treatment or even liver transplantation.

“Those things are important because that pathway gives clinicians an idea of how to do this properly,” he said.

“The key for clinicians is to make sure they understand, in the context of cirrhosis, some of the easy things that they can do to prevent AKI,” he continued. He added that the use of NSAIDs in these patients is “going to be problematic.”

Dr. Kamath has a relationship with Sequana Medical. Other authors’ relevant financial relationships are listed in the original article. Dr. Reau has relationships with Salix and Intercept. Dr. Younossi has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This article was updated 12/12/2022.

Acute kidney injury (AKI) in patients with cirrhosis is potentially preventable, and there are clear steps that can be taken to manage and reverse the condition, concludes a clinical practice update from the American Gastroenterological Association.

AKI occurs in 47% of patients hospitalized with complications of cirrhosis and in approximately 30% of outpatients with cirrhosis, resulting in a total cost in the United States of $4 billion, explained Patrick S. Kamath, MD, division of gastroenterology and hepatology, Mayo Medical School, Rochester, Minn., one of the authors of this update.

Moreover, Dr. Kamath told this news organization, among patients with cirrhosis and AKI, morbidity and mortality is sevenfold higher in comparison to those without cirrhosis, and repeated episodes of AKI increase the risk of progression to chronic kidney disease.

To provide practical advice for the clinical management of patients with cirrhosis and AKI, the authors conducted an expert review of the best available published evidence and gathered expert opinion.

The update was published online in Clinical Gastroenterology and Hepatology.
 

Some key takeaways

Among its 14 best practice statements, it describes three situations indicative of AKI:

• A serum creatinine increase of 0.3 mg/dL or more within 48 hours, or
• A serum creatinine increase of 50% or more from baseline, which is a stable serum creatinine in the past 3 months.
• Reduction in urine output of up to 0.5 mL/kg per hour for more than 6 hours.

The update also emphasizes the importance of an accurate diagnosis, inasmuch as not all cases of AKI are due to hepatorenal syndrome (HRS), for example. It goes on to advise that the specific type of AKI be identified through medical history and physical examination, as well as with blood biochemistry, urine microscopic examination, urine chemistry, selected urinary biomarkers, and renal ultrasound.

Additionally, it underscores the need to identify and treat infections and to closely monitor fluid status.

Nancy S. Reau, MD, Rush Medical College, Chicago, who was not involved in the update, commented to this news organization that fluid status is important when giving albumin replacement therapy because of the increased risk for pulmonary edema.

She also highlighted that this update advises against transjugular intrahepatic portosystemic shunts (TIPSs) as a specific treatment for HRS-AKI, noting that, although the 2022 North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension do not advocate for TIPS for this indication, they also indicated that there was enough evidence to advise against it.

In other key best practice advice statements, the update advises clinicians to hold diuretics and nonselective beta blockers and to discontinue nonsteroidal anti-inflammatory drugs (NSAIDs).
 

‘Timely’ update

Overall, Dr. Reau believes that the update is “timely, especially in light of the recent [U.S.] approval of terlipressin, which will change our treatment options.”

This update also supports the American Association for the Study of Liver Diseases (AASLD) 2021 Practice Guidance guidelines on HRS, she added.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., who was not involved in writing the update, told this news organization that the document is important because of the huge increase in mortality among patients with cirrhosis and AKI.

He commented that there has been much advancement in understanding the condition, with updated nomenclature and novel medical treatments, and that this makes the update timely.

Moreover, the update will help clinicians who are involved in the care of patients with cirrhosis, he added.

Dr. Younossi said the update offers a very clearly stated algorithm for how to identify patients whose condition is easily reversible with volume repletion, in comparison with those patients who require medical treatment or even liver transplantation.

“Those things are important because that pathway gives clinicians an idea of how to do this properly,” he said.

“The key for clinicians is to make sure they understand, in the context of cirrhosis, some of the easy things that they can do to prevent AKI,” he continued. He added that the use of NSAIDs in these patients is “going to be problematic.”

Dr. Kamath has a relationship with Sequana Medical. Other authors’ relevant financial relationships are listed in the original article. Dr. Reau has relationships with Salix and Intercept. Dr. Younossi has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This article was updated 12/12/2022.

Increasing mentorship opportunities for gastroenterology and hepatology residents and medical students from populations underrepresented in medicine is essential to increase diversity in the specialty and improve health disparities among patients, according to a special report published simultaneously in Gastroenterology and three other journals.

“This study helps to establish priorities for diversity, equity and inclusion in our field and informs future interventions to improve workforce diversity and eliminate health care disparities among the patients we serve,” Folasade P. May, MD, PhD, MPhil, the study’s corresponding author and an associate professor of medicine at the University of California, Los Angeles, said in a prepared statement.

The report, the result of a partnership between researchers at UCLA and the Intersociety Group on Diversity, reveals the findings of a survey aimed at assessing current perspectives on individuals underrepresented in medicine and health equity within gastroenterology and hepatology. The collaboration involved five gastroenterology professional societies: the American Association for the Study of Liver Disease; American College of Gastroenterology; American Gastroenterological Association; American Society of Gastrointestinal Endoscopy; and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

”The current racial and ethnic composition of the GI and hepatology workforce does not reflect the population of patients served or the current matriculants in medicine,” Harman K. Rahal, MD, of UCLA and Cedars-Sinai Medical Center, Los Angeles, and James H. Tabibian, MD, PhD, of UCLA and Olive View–UCLA Medical Center, and colleagues wrote. “As there are several conditions in GI and hepatology with disparities in incidence, treatment, and outcomes, representation of UIM [underrepresented in medicine] individuals is critical to address health disparities.”

The term “underrepresented in medicine” is defined by the Association of American Medical Colleges as “those racial and ethnic populations that are underrepresented in the medical profession relative to their numbers in the general population.” The authors explained that these groups “have traditionally included Latino (i.e., Latino/a/x), Black (or African American), Native American (namely, American Indian, Alaska Native, and Native Hawaiian), Pacific Islander, and mainland Puerto Rican individuals.”

The five gastroenterology and hepatology societies partnered with investigators at UCLA to develop a 33-question electronic survey “to determine perspectives of current racial, ethnic, and gender diversity within GI and hepatology; to assess current views on interventions needed to increase racial, ethnic, and gender diversity in the field; and to collect data on the experiences of UIM individuals and women in our field,” according to the report’s authors. The survey was then distributed to members of those societies, with 1,219 respondents.

The report found that inadequate representation of people from those underrepresented groups in the education and training pipeline was the most frequently reported barrier to improving racial and ethnic diversity in the field (35.4%), followed by insufficient racial and ethnic minority group representation in professional leadership (27.9%) and insufficient racial and ethnic minority group representation among practicing GI and hepatology professionals in the workplace (26.6%). Only 9% of fellows in GI and hepatology are from groups underrepresented in medicine, according to data from the Accreditation Council for Graduate Medical Education. Furthermore, one study has shown that the proportion of UIM in academic faculty has never exceeded 10% at each academic rank; there has even been a decline recently among junior academic faculty positions. That study also found that only 9% of academic gastroenterologists in the United states identify as underrepresented in medicine, with little change over the last decade.

Potential contributors to this low level of representation, the authors wrote, include “lack of racial and ethnic diversity in the medical training pipeline, nondiverse leadership, bias, racial discrimination, and the notion that UIM physicians may be less likely to promote themselves or be promoted.”

Another potential contributor, however, may be complacency within the field about the need to improve diversity and taking actions to do so.

Increasing mentorship opportunities for gastroenterology and hepatology residents and medical students from populations underrepresented in medicine is essential to increase diversity in the specialty and improve health disparities among patients, according to a special report published simultaneously in Gastroenterology and three other journals.

“This study helps to establish priorities for diversity, equity and inclusion in our field and informs future interventions to improve workforce diversity and eliminate health care disparities among the patients we serve,” Folasade P. May, MD, PhD, MPhil, the study’s corresponding author and an associate professor of medicine at the University of California, Los Angeles, said in a prepared statement.

The report, the result of a partnership between researchers at UCLA and the Intersociety Group on Diversity, reveals the findings of a survey aimed at assessing current perspectives on individuals underrepresented in medicine and health equity within gastroenterology and hepatology. The collaboration involved five gastroenterology professional societies: the American Association for the Study of Liver Disease; American College of Gastroenterology; American Gastroenterological Association; American Society of Gastrointestinal Endoscopy; and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

”The current racial and ethnic composition of the GI and hepatology workforce does not reflect the population of patients served or the current matriculants in medicine,” Harman K. Rahal, MD, of UCLA and Cedars-Sinai Medical Center, Los Angeles, and James H. Tabibian, MD, PhD, of UCLA and Olive View–UCLA Medical Center, and colleagues wrote. “As there are several conditions in GI and hepatology with disparities in incidence, treatment, and outcomes, representation of UIM [underrepresented in medicine] individuals is critical to address health disparities.”

The term “underrepresented in medicine” is defined by the Association of American Medical Colleges as “those racial and ethnic populations that are underrepresented in the medical profession relative to their numbers in the general population.” The authors explained that these groups “have traditionally included Latino (i.e., Latino/a/x), Black (or African American), Native American (namely, American Indian, Alaska Native, and Native Hawaiian), Pacific Islander, and mainland Puerto Rican individuals.”

The five gastroenterology and hepatology societies partnered with investigators at UCLA to develop a 33-question electronic survey “to determine perspectives of current racial, ethnic, and gender diversity within GI and hepatology; to assess current views on interventions needed to increase racial, ethnic, and gender diversity in the field; and to collect data on the experiences of UIM individuals and women in our field,” according to the report’s authors. The survey was then distributed to members of those societies, with 1,219 respondents.

The report found that inadequate representation of people from those underrepresented groups in the education and training pipeline was the most frequently reported barrier to improving racial and ethnic diversity in the field (35.4%), followed by insufficient racial and ethnic minority group representation in professional leadership (27.9%) and insufficient racial and ethnic minority group representation among practicing GI and hepatology professionals in the workplace (26.6%). Only 9% of fellows in GI and hepatology are from groups underrepresented in medicine, according to data from the Accreditation Council for Graduate Medical Education. Furthermore, one study has shown that the proportion of UIM in academic faculty has never exceeded 10% at each academic rank; there has even been a decline recently among junior academic faculty positions. That study also found that only 9% of academic gastroenterologists in the United states identify as underrepresented in medicine, with little change over the last decade.

Potential contributors to this low level of representation, the authors wrote, include “lack of racial and ethnic diversity in the medical training pipeline, nondiverse leadership, bias, racial discrimination, and the notion that UIM physicians may be less likely to promote themselves or be promoted.”

Another potential contributor, however, may be complacency within the field about the need to improve diversity and taking actions to do so.

Increasing mentorship opportunities for gastroenterology and hepatology residents and medical students from populations underrepresented in medicine is essential to increase diversity in the specialty and improve health disparities among patients, according to a special report published simultaneously in Gastroenterology and three other journals.

“This study helps to establish priorities for diversity, equity and inclusion in our field and informs future interventions to improve workforce diversity and eliminate health care disparities among the patients we serve,” Folasade P. May, MD, PhD, MPhil, the study’s corresponding author and an associate professor of medicine at the University of California, Los Angeles, said in a prepared statement.

The report, the result of a partnership between researchers at UCLA and the Intersociety Group on Diversity, reveals the findings of a survey aimed at assessing current perspectives on individuals underrepresented in medicine and health equity within gastroenterology and hepatology. The collaboration involved five gastroenterology professional societies: the American Association for the Study of Liver Disease; American College of Gastroenterology; American Gastroenterological Association; American Society of Gastrointestinal Endoscopy; and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

”The current racial and ethnic composition of the GI and hepatology workforce does not reflect the population of patients served or the current matriculants in medicine,” Harman K. Rahal, MD, of UCLA and Cedars-Sinai Medical Center, Los Angeles, and James H. Tabibian, MD, PhD, of UCLA and Olive View–UCLA Medical Center, and colleagues wrote. “As there are several conditions in GI and hepatology with disparities in incidence, treatment, and outcomes, representation of UIM [underrepresented in medicine] individuals is critical to address health disparities.”

The term “underrepresented in medicine” is defined by the Association of American Medical Colleges as “those racial and ethnic populations that are underrepresented in the medical profession relative to their numbers in the general population.” The authors explained that these groups “have traditionally included Latino (i.e., Latino/a/x), Black (or African American), Native American (namely, American Indian, Alaska Native, and Native Hawaiian), Pacific Islander, and mainland Puerto Rican individuals.”

The five gastroenterology and hepatology societies partnered with investigators at UCLA to develop a 33-question electronic survey “to determine perspectives of current racial, ethnic, and gender diversity within GI and hepatology; to assess current views on interventions needed to increase racial, ethnic, and gender diversity in the field; and to collect data on the experiences of UIM individuals and women in our field,” according to the report’s authors. The survey was then distributed to members of those societies, with 1,219 respondents.

The report found that inadequate representation of people from those underrepresented groups in the education and training pipeline was the most frequently reported barrier to improving racial and ethnic diversity in the field (35.4%), followed by insufficient racial and ethnic minority group representation in professional leadership (27.9%) and insufficient racial and ethnic minority group representation among practicing GI and hepatology professionals in the workplace (26.6%). Only 9% of fellows in GI and hepatology are from groups underrepresented in medicine, according to data from the Accreditation Council for Graduate Medical Education. Furthermore, one study has shown that the proportion of UIM in academic faculty has never exceeded 10% at each academic rank; there has even been a decline recently among junior academic faculty positions. That study also found that only 9% of academic gastroenterologists in the United states identify as underrepresented in medicine, with little change over the last decade.

Potential contributors to this low level of representation, the authors wrote, include “lack of racial and ethnic diversity in the medical training pipeline, nondiverse leadership, bias, racial discrimination, and the notion that UIM physicians may be less likely to promote themselves or be promoted.”

Another potential contributor, however, may be complacency within the field about the need to improve diversity and taking actions to do so.

The diversity of neuroendocrine tumors (NETs) – which includes variation in location, mutational profile, and response to therapy – may be due to divergent cellular origins in different tissue sites, according to a new study.

The pathogenesis of gastroenteropancreatic neoplasms (GEP-NENs) is poorly understood, in part because of a lack of modeling systems, according to Suzann Duan, PhD, and colleagues. They are a heterogeneous group of tumors that are increasingly prevalent in the United States. GEP-NENs arise from endocrine-producing cells and include gastric carcinoids, gastrinomas, and pancreatic NETs.

Despite the general mystery surrounding GEP-NENs, there is at least one clue in the form of the MEN1 gene. Both inherited and sporadic mutations of this gene are associated with GEP-NENs. Menin is a tumor suppressor protein, and previous studies have shown that inactivation of MEN1 leads to loss of that protein and is associated with endocrine tumors in the pancreas, pituitary, and upper GI tract.

In new research published in Cellular and Molecular Gastroenterology and Hepatology, researchers investigated the role of MEN1 in neuroendocrine cell development and traced it to a potential role in the development of NETs.

Patients with MEN1 mutations are at increased risk of gastrinomas, which lead to increased production of the peptide hormone gastrin. Gastrin increases acid production and can lead to hyperplasia in parietal and enterochromaffin cells. These generally develop in Brunner’s glands within the submucosa of the duodenum. At time of diagnosis, more than half of such tumors have developed lymph node metastases.

It remains unclear how loss of MEN1 suppresses gastrin production. Previous research showed that homozygous MEN1 deletion in mice is lethal to embryos, while leaving one copy intact leads to heightened risk of endocrine tumors in the pancreas and pituitary gland, but not in the GI tract. The studies did not reveal the tumor’s origin cell.

The researchers developed a novel mouse model in which MEN1 is conditionally deleted from the GI tract epithelium. This led to hyperplasia of gastrin-producing cells (G cells) in the antrum, as well as hypergastrinemia and development of gastric NETs. Exposure to a proton pump inhibitor accelerated gastric NET development, and the researchers identified expansion of enteric glial cells that expressed gastrin and GFAP. Glial cells that differentiated into endocrine phenotype were associated with a reversible loss of menin. “Taken together, these observations suggest that hyperplastic G cells might emerge from reprogrammed neural crest–derived cells in addition to endoderm-derived enteroendocrine cells,” the authors wrote.

That idea is supported by previous research indicating that multipotent glial cells expressing GFAP or SOX10 may play a developmental role in formation of neuroendocrine cells.

With this in mind, the researchers deleted MEN1 in GFAP-expressing cells to see if it would promote neuroendocrine cell development.

The result was hyperplasia in the gastric antrum and NETs in the pituitary and pancreas. To the researchers’ surprise, NET development was associated with loss of GFAP expression as well as activation of neuronal and neuroendocrine-related genes in the stomach, pancreas, and pituitary. There was universal reduction of GFAP protein expression in pituitary and pancreatic NETs, but GFAP transcript levels stayed steady in the gastric antra despite a reduction in GFAP-reporter expression. This could indicate that the menin protein interacts with GFAP. If so, eliminating menin in GFAP-positive cells could change the localization of GFAP, which may in turn lead to changes in glial cell identity.

When the researchers compared transcriptomes of hyperplastic antral tissues to well-differentiated NETs, they found that NETs exhibited a greater loss of glial-restricted progenitor lineage–associated genes as well as more downregulation of gliogenesis-directing factors. “Thus, the transition from a glial-to-neuronal cell phenotype appears to promote the progression from neuroendocrine cell hyperplasia to tumor development,” the authors wrote. They also found that NETs have higher levels of expression of genes associated with neural stem and progenitor cells, as well as upregulation of factors secreted from neural crest cells that promote neurogenesis and restrict the glial cell fate. Many of these factors are part of the Hedgehog signaling pathway, and menin is known to repress Hedgehog signaling.

Intestinal glial cells have a high degree of plasticity. They can become neuronal progenitor cells and yet they can dedifferentiate to differentiate again into other cell lineages.

The research could eventually lead to identification of unique cells-of-origin for these tumors. The authors say that the diversity of the tumors – which includes variation in location, mutational profile, and response to therapy – may be due to divergent cellular origins in different tissue sites. “Defining the cells-of-origin and the events preceding neoplastic transformation will be critical to informing molecular signaling pathways that can then be targeted therapeutically,” the authors wrote.

The authors disclosed no conflicts of interest.

The diversity of neuroendocrine tumors (NETs) – which includes variation in location, mutational profile, and response to therapy – may be due to divergent cellular origins in different tissue sites, according to a new study.

The pathogenesis of gastroenteropancreatic neoplasms (GEP-NENs) is poorly understood, in part because of a lack of modeling systems, according to Suzann Duan, PhD, and colleagues. They are a heterogeneous group of tumors that are increasingly prevalent in the United States. GEP-NENs arise from endocrine-producing cells and include gastric carcinoids, gastrinomas, and pancreatic NETs.

Despite the general mystery surrounding GEP-NENs, there is at least one clue in the form of the MEN1 gene. Both inherited and sporadic mutations of this gene are associated with GEP-NENs. Menin is a tumor suppressor protein, and previous studies have shown that inactivation of MEN1 leads to loss of that protein and is associated with endocrine tumors in the pancreas, pituitary, and upper GI tract.

In new research published in Cellular and Molecular Gastroenterology and Hepatology, researchers investigated the role of MEN1 in neuroendocrine cell development and traced it to a potential role in the development of NETs.

Patients with MEN1 mutations are at increased risk of gastrinomas, which lead to increased production of the peptide hormone gastrin. Gastrin increases acid production and can lead to hyperplasia in parietal and enterochromaffin cells. These generally develop in Brunner’s glands within the submucosa of the duodenum. At time of diagnosis, more than half of such tumors have developed lymph node metastases.

It remains unclear how loss of MEN1 suppresses gastrin production. Previous research showed that homozygous MEN1 deletion in mice is lethal to embryos, while leaving one copy intact leads to heightened risk of endocrine tumors in the pancreas and pituitary gland, but not in the GI tract. The studies did not reveal the tumor’s origin cell.

The researchers developed a novel mouse model in which MEN1 is conditionally deleted from the GI tract epithelium. This led to hyperplasia of gastrin-producing cells (G cells) in the antrum, as well as hypergastrinemia and development of gastric NETs. Exposure to a proton pump inhibitor accelerated gastric NET development, and the researchers identified expansion of enteric glial cells that expressed gastrin and GFAP. Glial cells that differentiated into endocrine phenotype were associated with a reversible loss of menin. “Taken together, these observations suggest that hyperplastic G cells might emerge from reprogrammed neural crest–derived cells in addition to endoderm-derived enteroendocrine cells,” the authors wrote.

That idea is supported by previous research indicating that multipotent glial cells expressing GFAP or SOX10 may play a developmental role in formation of neuroendocrine cells.

With this in mind, the researchers deleted MEN1 in GFAP-expressing cells to see if it would promote neuroendocrine cell development.

The result was hyperplasia in the gastric antrum and NETs in the pituitary and pancreas. To the researchers’ surprise, NET development was associated with loss of GFAP expression as well as activation of neuronal and neuroendocrine-related genes in the stomach, pancreas, and pituitary. There was universal reduction of GFAP protein expression in pituitary and pancreatic NETs, but GFAP transcript levels stayed steady in the gastric antra despite a reduction in GFAP-reporter expression. This could indicate that the menin protein interacts with GFAP. If so, eliminating menin in GFAP-positive cells could change the localization of GFAP, which may in turn lead to changes in glial cell identity.

When the researchers compared transcriptomes of hyperplastic antral tissues to well-differentiated NETs, they found that NETs exhibited a greater loss of glial-restricted progenitor lineage–associated genes as well as more downregulation of gliogenesis-directing factors. “Thus, the transition from a glial-to-neuronal cell phenotype appears to promote the progression from neuroendocrine cell hyperplasia to tumor development,” the authors wrote. They also found that NETs have higher levels of expression of genes associated with neural stem and progenitor cells, as well as upregulation of factors secreted from neural crest cells that promote neurogenesis and restrict the glial cell fate. Many of these factors are part of the Hedgehog signaling pathway, and menin is known to repress Hedgehog signaling.

Intestinal glial cells have a high degree of plasticity. They can become neuronal progenitor cells and yet they can dedifferentiate to differentiate again into other cell lineages.

The research could eventually lead to identification of unique cells-of-origin for these tumors. The authors say that the diversity of the tumors – which includes variation in location, mutational profile, and response to therapy – may be due to divergent cellular origins in different tissue sites. “Defining the cells-of-origin and the events preceding neoplastic transformation will be critical to informing molecular signaling pathways that can then be targeted therapeutically,” the authors wrote.

The authors disclosed no conflicts of interest.

The diversity of neuroendocrine tumors (NETs) – which includes variation in location, mutational profile, and response to therapy – may be due to divergent cellular origins in different tissue sites, according to a new study.

The pathogenesis of gastroenteropancreatic neoplasms (GEP-NENs) is poorly understood, in part because of a lack of modeling systems, according to Suzann Duan, PhD, and colleagues. They are a heterogeneous group of tumors that are increasingly prevalent in the United States. GEP-NENs arise from endocrine-producing cells and include gastric carcinoids, gastrinomas, and pancreatic NETs.

Despite the general mystery surrounding GEP-NENs, there is at least one clue in the form of the MEN1 gene. Both inherited and sporadic mutations of this gene are associated with GEP-NENs. Menin is a tumor suppressor protein, and previous studies have shown that inactivation of MEN1 leads to loss of that protein and is associated with endocrine tumors in the pancreas, pituitary, and upper GI tract.

In new research published in Cellular and Molecular Gastroenterology and Hepatology, researchers investigated the role of MEN1 in neuroendocrine cell development and traced it to a potential role in the development of NETs.

Patients with MEN1 mutations are at increased risk of gastrinomas, which lead to increased production of the peptide hormone gastrin. Gastrin increases acid production and can lead to hyperplasia in parietal and enterochromaffin cells. These generally develop in Brunner’s glands within the submucosa of the duodenum. At time of diagnosis, more than half of such tumors have developed lymph node metastases.

It remains unclear how loss of MEN1 suppresses gastrin production. Previous research showed that homozygous MEN1 deletion in mice is lethal to embryos, while leaving one copy intact leads to heightened risk of endocrine tumors in the pancreas and pituitary gland, but not in the GI tract. The studies did not reveal the tumor’s origin cell.

The researchers developed a novel mouse model in which MEN1 is conditionally deleted from the GI tract epithelium. This led to hyperplasia of gastrin-producing cells (G cells) in the antrum, as well as hypergastrinemia and development of gastric NETs. Exposure to a proton pump inhibitor accelerated gastric NET development, and the researchers identified expansion of enteric glial cells that expressed gastrin and GFAP. Glial cells that differentiated into endocrine phenotype were associated with a reversible loss of menin. “Taken together, these observations suggest that hyperplastic G cells might emerge from reprogrammed neural crest–derived cells in addition to endoderm-derived enteroendocrine cells,” the authors wrote.

That idea is supported by previous research indicating that multipotent glial cells expressing GFAP or SOX10 may play a developmental role in formation of neuroendocrine cells.

With this in mind, the researchers deleted MEN1 in GFAP-expressing cells to see if it would promote neuroendocrine cell development.

The result was hyperplasia in the gastric antrum and NETs in the pituitary and pancreas. To the researchers’ surprise, NET development was associated with loss of GFAP expression as well as activation of neuronal and neuroendocrine-related genes in the stomach, pancreas, and pituitary. There was universal reduction of GFAP protein expression in pituitary and pancreatic NETs, but GFAP transcript levels stayed steady in the gastric antra despite a reduction in GFAP-reporter expression. This could indicate that the menin protein interacts with GFAP. If so, eliminating menin in GFAP-positive cells could change the localization of GFAP, which may in turn lead to changes in glial cell identity.

When the researchers compared transcriptomes of hyperplastic antral tissues to well-differentiated NETs, they found that NETs exhibited a greater loss of glial-restricted progenitor lineage–associated genes as well as more downregulation of gliogenesis-directing factors. “Thus, the transition from a glial-to-neuronal cell phenotype appears to promote the progression from neuroendocrine cell hyperplasia to tumor development,” the authors wrote. They also found that NETs have higher levels of expression of genes associated with neural stem and progenitor cells, as well as upregulation of factors secreted from neural crest cells that promote neurogenesis and restrict the glial cell fate. Many of these factors are part of the Hedgehog signaling pathway, and menin is known to repress Hedgehog signaling.

Intestinal glial cells have a high degree of plasticity. They can become neuronal progenitor cells and yet they can dedifferentiate to differentiate again into other cell lineages.

The research could eventually lead to identification of unique cells-of-origin for these tumors. The authors say that the diversity of the tumors – which includes variation in location, mutational profile, and response to therapy – may be due to divergent cellular origins in different tissue sites. “Defining the cells-of-origin and the events preceding neoplastic transformation will be critical to informing molecular signaling pathways that can then be targeted therapeutically,” the authors wrote.

The authors disclosed no conflicts of interest.