News

The US House Appropriations Committee approved a $453 billion budget to fund the US Department of Veterans (VA), military construction, and other programs in 2026 by a 36-27 vote. The bill includes $34 billion proposed for community care programs, an increase of > 50% from 2025 community care funding levels.

The discretionary funding would also send $2.5 billion to the VA electronic health records modernization program. Mandatory spending includes $53 billion for the Toxic Exposures Fund, which supports benefits and health care costs associated with the PACT Act.

Although VA budget bills are typically bipartisan in nature, this bill passed by a much narrower margin than is typical. Rep. Debbie Wasserman Schultz (D-FL), ranking member of the Military Construction, Veterans Affairs and Related Agencies Appropriations Subcommittee, said the bill “diverts far too many resources away from the vital, VA-based care that veterans consistently tell us they want, and it pushes them into pricier, subpar corporate hospitals.” 

Committee Democrats offered dozens of amendments. All amendments were rejected except for a modification that would block staff reductions at the Veterans Crisis Line and other VA suicide prevention programs.

The bill now moves to the full House of Representatives for consideration. House leaders have not yet announced when that vote will take place; the House is in recess the week of June 16, 2025. 

The committee also released the Fiscal Year 2026 Military Construction, Veterans Affairs, and Related Agencies Bill, which would spend > $83 million, a 22% increase over the 2025.

The US House Appropriations Committee approved a $453 billion budget to fund the US Department of Veterans (VA), military construction, and other programs in 2026 by a 36-27 vote. The bill includes $34 billion proposed for community care programs, an increase of > 50% from 2025 community care funding levels.

The discretionary funding would also send $2.5 billion to the VA electronic health records modernization program. Mandatory spending includes $53 billion for the Toxic Exposures Fund, which supports benefits and health care costs associated with the PACT Act.

Although VA budget bills are typically bipartisan in nature, this bill passed by a much narrower margin than is typical. Rep. Debbie Wasserman Schultz (D-FL), ranking member of the Military Construction, Veterans Affairs and Related Agencies Appropriations Subcommittee, said the bill “diverts far too many resources away from the vital, VA-based care that veterans consistently tell us they want, and it pushes them into pricier, subpar corporate hospitals.” 

Committee Democrats offered dozens of amendments. All amendments were rejected except for a modification that would block staff reductions at the Veterans Crisis Line and other VA suicide prevention programs.

The bill now moves to the full House of Representatives for consideration. House leaders have not yet announced when that vote will take place; the House is in recess the week of June 16, 2025. 

The committee also released the Fiscal Year 2026 Military Construction, Veterans Affairs, and Related Agencies Bill, which would spend > $83 million, a 22% increase over the 2025.

The US House Appropriations Committee approved a $453 billion budget to fund the US Department of Veterans (VA), military construction, and other programs in 2026 by a 36-27 vote. The bill includes $34 billion proposed for community care programs, an increase of > 50% from 2025 community care funding levels.

The discretionary funding would also send $2.5 billion to the VA electronic health records modernization program. Mandatory spending includes $53 billion for the Toxic Exposures Fund, which supports benefits and health care costs associated with the PACT Act.

Although VA budget bills are typically bipartisan in nature, this bill passed by a much narrower margin than is typical. Rep. Debbie Wasserman Schultz (D-FL), ranking member of the Military Construction, Veterans Affairs and Related Agencies Appropriations Subcommittee, said the bill “diverts far too many resources away from the vital, VA-based care that veterans consistently tell us they want, and it pushes them into pricier, subpar corporate hospitals.” 

Committee Democrats offered dozens of amendments. All amendments were rejected except for a modification that would block staff reductions at the Veterans Crisis Line and other VA suicide prevention programs.

The bill now moves to the full House of Representatives for consideration. House leaders have not yet announced when that vote will take place; the House is in recess the week of June 16, 2025. 

The committee also released the Fiscal Year 2026 Military Construction, Veterans Affairs, and Related Agencies Bill, which would spend > $83 million, a 22% increase over the 2025.

Hepatic encephalopathy (HE) is no longer a rare complication – it’s an urgent clinical reality that’s a leading cause of hospitalization in patients with cirrhosis.¹ HE can be deceptively subtle or profoundly severe, presenting with a wide clinical spectrum – from mild cognitive slowing to life-threatening coma. Without clear disease biomarkers, HE remains a diagnosis of exclusion, making it critical for clinicians to remain vigilant, especially in patients with chronic liver disease (CLD).

The incidence of CLD is climbing, fueled by rising rates of alcohol-associated liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), and hepatitis C, which is often undiagnosed. For example:

• More than 2 million Americans had alcohol-associated cirrhosis as of 2017.²
• Currently, 38% of all adults and 7–14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to more than 55%.³
• The economic burden is staggering – from $1 billion⁴ in 2003 to over $7 billion⁵ in hospital costs for cirrhosis-related admissions today.

These figures aren’t just statistics – they represent a growing population of patients who are at risk of developing HE, sometimes without ever receiving a proper diagnosis or follow-up care.

Because HE mimics many other forms of neurological dysfunction – delirium, alcohol intoxication, diabetes-related confusion – it can be easy to miss or misdiagnose. But differentiating HE from other causes of altered mental status is critical, especially for patients who may ultimately require liver transplantation.^{6, 7}

Moreover, patients frequently leave the hospital without adequate education or maintenance medication for episodic overt HE. Without coordinated follow-up between primary care, hepatology, and caregivers, these patients are at risk for recurrence.

To close these practice gaps, education is key. AGA’s course, “Missing the Mark: Hepatic Encephalopathy,” provides clinicians with up-to-date guidance on:

• The changing epidemiology of cirrhosis and undiagnosed cirrhosis for patients with liver disease.
• Assessment guidelines and best practices for HE diagnosis and management.
• How to develop transition-of-care plans with patients, caretakers, and specialty providers after an initial HE diagnosis.

Take the course today: https://tinyurl.com/3muwhmj5

Don’t wait until HE is an emergency. Equip yourself with the tools to recognize it earlier, treat it effectively, and coordinate better care.

References

1. Wolf, DC. Hepatic Encephalopathy. Medscape. 2020 May 1. Retrieved from: https://emedicine.medscape.com/article/186101-overview

2. Singal AK, Mathurin P. Diagnosis and treatment of alcohol-associated liver disease A review. JAMA. 2021 Jul. doi:10.1001/jama.2021.7683.

3. Younossi ZM, et al. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol. 2025 Feb. doi: 10.3350/cmh.2024.0431.

4. Vilstrup H, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug. doi: 10.1002/hep.27210.

5. Desai AP, et al. Increasing Economic Burden in Hospitalized Patients With Cirrhosis: Analysis of a National Database. Clin Transl Gastroenterol. 2019 Jul. doi: 10.14309/ctg.0000000000000062.

6. Serper M, et al. Hepatic encephalopathy predicts early post-transplant cognitive and functional impairment: The Livcog cohort study. Hepatol Commun. 2025 Apr. doi: 10.1097/HC9.0000000000000696.

7. Montagnese S, Bajaj JS. Impact of Hepatic Encephalopathy in Cirrhosis on Quality-of-Life Issues. Drugs. 2019 Jan. doi: 10.1007/s40265-018-1019-y.

Hepatic encephalopathy (HE) is no longer a rare complication – it’s an urgent clinical reality that’s a leading cause of hospitalization in patients with cirrhosis.¹ HE can be deceptively subtle or profoundly severe, presenting with a wide clinical spectrum – from mild cognitive slowing to life-threatening coma. Without clear disease biomarkers, HE remains a diagnosis of exclusion, making it critical for clinicians to remain vigilant, especially in patients with chronic liver disease (CLD).

The incidence of CLD is climbing, fueled by rising rates of alcohol-associated liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), and hepatitis C, which is often undiagnosed. For example:

• More than 2 million Americans had alcohol-associated cirrhosis as of 2017.²
• Currently, 38% of all adults and 7–14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to more than 55%.³
• The economic burden is staggering – from $1 billion⁴ in 2003 to over $7 billion⁵ in hospital costs for cirrhosis-related admissions today.

These figures aren’t just statistics – they represent a growing population of patients who are at risk of developing HE, sometimes without ever receiving a proper diagnosis or follow-up care.

Because HE mimics many other forms of neurological dysfunction – delirium, alcohol intoxication, diabetes-related confusion – it can be easy to miss or misdiagnose. But differentiating HE from other causes of altered mental status is critical, especially for patients who may ultimately require liver transplantation.^{6, 7}

Moreover, patients frequently leave the hospital without adequate education or maintenance medication for episodic overt HE. Without coordinated follow-up between primary care, hepatology, and caregivers, these patients are at risk for recurrence.

To close these practice gaps, education is key. AGA’s course, “Missing the Mark: Hepatic Encephalopathy,” provides clinicians with up-to-date guidance on:

• The changing epidemiology of cirrhosis and undiagnosed cirrhosis for patients with liver disease.
• Assessment guidelines and best practices for HE diagnosis and management.
• How to develop transition-of-care plans with patients, caretakers, and specialty providers after an initial HE diagnosis.

Take the course today: https://tinyurl.com/3muwhmj5

Don’t wait until HE is an emergency. Equip yourself with the tools to recognize it earlier, treat it effectively, and coordinate better care.

References

1. Wolf, DC. Hepatic Encephalopathy. Medscape. 2020 May 1. Retrieved from: https://emedicine.medscape.com/article/186101-overview

2. Singal AK, Mathurin P. Diagnosis and treatment of alcohol-associated liver disease A review. JAMA. 2021 Jul. doi:10.1001/jama.2021.7683.

3. Younossi ZM, et al. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol. 2025 Feb. doi: 10.3350/cmh.2024.0431.

4. Vilstrup H, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug. doi: 10.1002/hep.27210.

5. Desai AP, et al. Increasing Economic Burden in Hospitalized Patients With Cirrhosis: Analysis of a National Database. Clin Transl Gastroenterol. 2019 Jul. doi: 10.14309/ctg.0000000000000062.

6. Serper M, et al. Hepatic encephalopathy predicts early post-transplant cognitive and functional impairment: The Livcog cohort study. Hepatol Commun. 2025 Apr. doi: 10.1097/HC9.0000000000000696.

7. Montagnese S, Bajaj JS. Impact of Hepatic Encephalopathy in Cirrhosis on Quality-of-Life Issues. Drugs. 2019 Jan. doi: 10.1007/s40265-018-1019-y.

Hepatic encephalopathy (HE) is no longer a rare complication – it’s an urgent clinical reality that’s a leading cause of hospitalization in patients with cirrhosis.¹ HE can be deceptively subtle or profoundly severe, presenting with a wide clinical spectrum – from mild cognitive slowing to life-threatening coma. Without clear disease biomarkers, HE remains a diagnosis of exclusion, making it critical for clinicians to remain vigilant, especially in patients with chronic liver disease (CLD).

The incidence of CLD is climbing, fueled by rising rates of alcohol-associated liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), and hepatitis C, which is often undiagnosed. For example:

• More than 2 million Americans had alcohol-associated cirrhosis as of 2017.²
• Currently, 38% of all adults and 7–14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to more than 55%.³
• The economic burden is staggering – from $1 billion⁴ in 2003 to over $7 billion⁵ in hospital costs for cirrhosis-related admissions today.

These figures aren’t just statistics – they represent a growing population of patients who are at risk of developing HE, sometimes without ever receiving a proper diagnosis or follow-up care.

Because HE mimics many other forms of neurological dysfunction – delirium, alcohol intoxication, diabetes-related confusion – it can be easy to miss or misdiagnose. But differentiating HE from other causes of altered mental status is critical, especially for patients who may ultimately require liver transplantation.^{6, 7}

Moreover, patients frequently leave the hospital without adequate education or maintenance medication for episodic overt HE. Without coordinated follow-up between primary care, hepatology, and caregivers, these patients are at risk for recurrence.

To close these practice gaps, education is key. AGA’s course, “Missing the Mark: Hepatic Encephalopathy,” provides clinicians with up-to-date guidance on:

• The changing epidemiology of cirrhosis and undiagnosed cirrhosis for patients with liver disease.
• Assessment guidelines and best practices for HE diagnosis and management.
• How to develop transition-of-care plans with patients, caretakers, and specialty providers after an initial HE diagnosis.

Take the course today: https://tinyurl.com/3muwhmj5

Don’t wait until HE is an emergency. Equip yourself with the tools to recognize it earlier, treat it effectively, and coordinate better care.

References

1. Wolf, DC. Hepatic Encephalopathy. Medscape. 2020 May 1. Retrieved from: https://emedicine.medscape.com/article/186101-overview

2. Singal AK, Mathurin P. Diagnosis and treatment of alcohol-associated liver disease A review. JAMA. 2021 Jul. doi:10.1001/jama.2021.7683.

3. Younossi ZM, et al. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol. 2025 Feb. doi: 10.3350/cmh.2024.0431.

4. Vilstrup H, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug. doi: 10.1002/hep.27210.

5. Desai AP, et al. Increasing Economic Burden in Hospitalized Patients With Cirrhosis: Analysis of a National Database. Clin Transl Gastroenterol. 2019 Jul. doi: 10.14309/ctg.0000000000000062.

6. Serper M, et al. Hepatic encephalopathy predicts early post-transplant cognitive and functional impairment: The Livcog cohort study. Hepatol Commun. 2025 Apr. doi: 10.1097/HC9.0000000000000696.

7. Montagnese S, Bajaj JS. Impact of Hepatic Encephalopathy in Cirrhosis on Quality-of-Life Issues. Drugs. 2019 Jan. doi: 10.1007/s40265-018-1019-y.

SAN DIEGO –A novel gene risk score, informed by machine learning, predicted weight-loss outcomes after Roux-en-Y gastric bypass (RYGB) surgery, a new analysis showed.

The findings suggested that the MyPhenome test (Phenomix Sciences) can help clinicians identify the patients most likely to benefit from bariatric procedures and at a greater risk for long-term weight regain after surgery.

“Patients with both a high genetic risk score and rare mutations in the leptin-melanocortin pathway (LMP) had significantly worse outcomes, maintaining only 4.9% total body weight loss [TBWL] over 15 years compared to up to 24.8% in other genetic groups,” Phenomix Sciences Co-founder Andres Acosta, MD, PhD, told GI & Hepatology News.

The study included details on the score’s development and predictive capability. It was presented at Digestive Disease Week^® (DDW) 2025

‘More Precise Bariatric Care’

The researchers recently developed a machine learning-assisted gene risk score for calories to satiation (CTSGRS), which mainly involves genes in the LMP. To assess the role of the score with or without LMP gene variants on weight loss and weight recurrence after RYGB, they identified 707 patients with a history of bariatric procedures from the Mayo Clinic Biobank. Patients with duodenal switch, revisional procedures, or who used antiobesity medications or became pregnant during follow-up were excluded.

To make predictions for 442 of the patients, the team first collected anthropometric data up to 15 years after RYGB. Then they used a two-step approach: Assessing for monogenic variants in the LMP and defining participants as carriers (LMP+) or noncarriers (LMP-). Then they defined the gene risk score (CTSGRS+ or CTSGRS-).

The result was four groups: LMP+/CTSGRS+, LMP+/CTSGRS-, LMP-/CTSGRS+, and LMP-/CTSGRS-. Multiple regression analysis was used to analyze TBWL percentage (TBWL%) between the groups at different timepoints, adjusting for baseline weight, age, and gender.

At the 10-year follow-up, the LMP+/CTSGRS+ group demonstrated a significantly higher weight recurrence (regain) of TBW% compared to the other groups.

At 15 years post-RYGB, the mean TBWL% for LMP+/CTSGRS+ was -4.9 vs -20.3 for LMP+/CTSGRS-, -18.0 for LMP-/CTSGRS+, and -24.8 for LMP-/CTSGRS-.

Further analyses showed that the LMP+/CTSGRS+ group had significantly less weight loss than LMP+/CTSGRS- and LMP-/CTSGRS- groups.

Based on the findings, the authors wrote, “Genotyping patients could improve the implementation of individualized weight-loss interventions, enhance weight-loss outcomes, and/or may explain one of the etiological factors associated with weight recurrence after RYGB.”

Acosta noted, “We’re actively expanding our research to include more diverse populations by age, sex, and race. This includes ongoing analysis to understand whether certain demographic or physiological characteristics affect how the test performs, particularly in the context of bariatric surgery.”

The team also is investigating the benefits of phenotyping for obesity comorbidities such as heart disease and diabetes, he said, and exploring whether early interventions in high-risk patients can prevent long-term weight regain and improve outcomes.

In addition, Acosta said, the team recently launched “the first prospective, placebo-controlled clinical trial using the MyPhenome test to predict response to semaglutide.” That study is based on earlier findings showing that patients identified with a Hungry Gut phenotype lost nearly twice as much weight on semaglutide compared with those who tested negative.

Overall, he concluded, “These findings open the door to more precise bariatric care. When we understand a patient’s biological drivers of obesity, we can make better decisions about the right procedure, follow-up, and long-term support. This moves us away from a one-size-fits-all model to care rooted in each patient’s unique biology.”

 

Potentially Paradigm-Shifting

Onur Kutlu, MD, associate professor of surgery and director of the Metabolic Surgery and Metabolic Health Program at the Miller School of Medicine, University of Miami, in Miami, Florida, commented on the study for GI & Hepatology News. “By integrating polygenic risk scores into predictive models, the authors offer an innovative method for identifying patients at elevated risk for weight regain following RYGB.”

“Their findings support the hypothesis that genetic predisposition — particularly involving energy homeostasis pathways — may underlie differential postoperative trajectories,” he said. “This approach has the potential to shift the paradigm from reactive to proactive management of weight recurrence.”

Because current options for treat weight regain are “suboptimal,” he said, “prevention becomes paramount. Preoperative identification of high-risk individuals could inform surgical decision-making, enable earlier interventions, and facilitate personalized postoperative monitoring and support.”

“If validated in larger, prospective cohorts, genetic risk stratification could enhance the precision of bariatric care and improve long-term outcomes,” he added. “Future studies should aim to validate these genetic models across diverse populations and explore how integration of behavioral, psychological, and genetic data may further refine patient selection and care pathways.”

The study was funded by Mayo Clinic and Phenomix Sciences. Gila Therapeutics and Phenomix Sciences licensed Acosta’s research technologies from the University of Florida and Mayo Clinic. Acosta declared receiving consultant fees in the past 5 years from Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, BI, Currax, Nestle, Phenomix Sciences, Bausch Health, and RareDiseases, as well as funding support from the National Institutes of Health, Vivus Pharmaceuticals, Novo Nordisk, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical, and Rhythm Pharmaceuticals. Kutlu declared having no conflicts of interest.

A version of this article appeared on Medscape.com.

SAN DIEGO –A novel gene risk score, informed by machine learning, predicted weight-loss outcomes after Roux-en-Y gastric bypass (RYGB) surgery, a new analysis showed.

The findings suggested that the MyPhenome test (Phenomix Sciences) can help clinicians identify the patients most likely to benefit from bariatric procedures and at a greater risk for long-term weight regain after surgery.

“Patients with both a high genetic risk score and rare mutations in the leptin-melanocortin pathway (LMP) had significantly worse outcomes, maintaining only 4.9% total body weight loss [TBWL] over 15 years compared to up to 24.8% in other genetic groups,” Phenomix Sciences Co-founder Andres Acosta, MD, PhD, told GI & Hepatology News.

The study included details on the score’s development and predictive capability. It was presented at Digestive Disease Week^® (DDW) 2025

‘More Precise Bariatric Care’

The researchers recently developed a machine learning-assisted gene risk score for calories to satiation (CTSGRS), which mainly involves genes in the LMP. To assess the role of the score with or without LMP gene variants on weight loss and weight recurrence after RYGB, they identified 707 patients with a history of bariatric procedures from the Mayo Clinic Biobank. Patients with duodenal switch, revisional procedures, or who used antiobesity medications or became pregnant during follow-up were excluded.

To make predictions for 442 of the patients, the team first collected anthropometric data up to 15 years after RYGB. Then they used a two-step approach: Assessing for monogenic variants in the LMP and defining participants as carriers (LMP+) or noncarriers (LMP-). Then they defined the gene risk score (CTSGRS+ or CTSGRS-).

The result was four groups: LMP+/CTSGRS+, LMP+/CTSGRS-, LMP-/CTSGRS+, and LMP-/CTSGRS-. Multiple regression analysis was used to analyze TBWL percentage (TBWL%) between the groups at different timepoints, adjusting for baseline weight, age, and gender.

At the 10-year follow-up, the LMP+/CTSGRS+ group demonstrated a significantly higher weight recurrence (regain) of TBW% compared to the other groups.

At 15 years post-RYGB, the mean TBWL% for LMP+/CTSGRS+ was -4.9 vs -20.3 for LMP+/CTSGRS-, -18.0 for LMP-/CTSGRS+, and -24.8 for LMP-/CTSGRS-.

Further analyses showed that the LMP+/CTSGRS+ group had significantly less weight loss than LMP+/CTSGRS- and LMP-/CTSGRS- groups.

Based on the findings, the authors wrote, “Genotyping patients could improve the implementation of individualized weight-loss interventions, enhance weight-loss outcomes, and/or may explain one of the etiological factors associated with weight recurrence after RYGB.”

Acosta noted, “We’re actively expanding our research to include more diverse populations by age, sex, and race. This includes ongoing analysis to understand whether certain demographic or physiological characteristics affect how the test performs, particularly in the context of bariatric surgery.”

The team also is investigating the benefits of phenotyping for obesity comorbidities such as heart disease and diabetes, he said, and exploring whether early interventions in high-risk patients can prevent long-term weight regain and improve outcomes.

In addition, Acosta said, the team recently launched “the first prospective, placebo-controlled clinical trial using the MyPhenome test to predict response to semaglutide.” That study is based on earlier findings showing that patients identified with a Hungry Gut phenotype lost nearly twice as much weight on semaglutide compared with those who tested negative.

Overall, he concluded, “These findings open the door to more precise bariatric care. When we understand a patient’s biological drivers of obesity, we can make better decisions about the right procedure, follow-up, and long-term support. This moves us away from a one-size-fits-all model to care rooted in each patient’s unique biology.”

 

Potentially Paradigm-Shifting

Onur Kutlu, MD, associate professor of surgery and director of the Metabolic Surgery and Metabolic Health Program at the Miller School of Medicine, University of Miami, in Miami, Florida, commented on the study for GI & Hepatology News. “By integrating polygenic risk scores into predictive models, the authors offer an innovative method for identifying patients at elevated risk for weight regain following RYGB.”

“Their findings support the hypothesis that genetic predisposition — particularly involving energy homeostasis pathways — may underlie differential postoperative trajectories,” he said. “This approach has the potential to shift the paradigm from reactive to proactive management of weight recurrence.”

Because current options for treat weight regain are “suboptimal,” he said, “prevention becomes paramount. Preoperative identification of high-risk individuals could inform surgical decision-making, enable earlier interventions, and facilitate personalized postoperative monitoring and support.”

“If validated in larger, prospective cohorts, genetic risk stratification could enhance the precision of bariatric care and improve long-term outcomes,” he added. “Future studies should aim to validate these genetic models across diverse populations and explore how integration of behavioral, psychological, and genetic data may further refine patient selection and care pathways.”

The study was funded by Mayo Clinic and Phenomix Sciences. Gila Therapeutics and Phenomix Sciences licensed Acosta’s research technologies from the University of Florida and Mayo Clinic. Acosta declared receiving consultant fees in the past 5 years from Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, BI, Currax, Nestle, Phenomix Sciences, Bausch Health, and RareDiseases, as well as funding support from the National Institutes of Health, Vivus Pharmaceuticals, Novo Nordisk, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical, and Rhythm Pharmaceuticals. Kutlu declared having no conflicts of interest.

A version of this article appeared on Medscape.com.

SAN DIEGO –A novel gene risk score, informed by machine learning, predicted weight-loss outcomes after Roux-en-Y gastric bypass (RYGB) surgery, a new analysis showed.

The findings suggested that the MyPhenome test (Phenomix Sciences) can help clinicians identify the patients most likely to benefit from bariatric procedures and at a greater risk for long-term weight regain after surgery.

“Patients with both a high genetic risk score and rare mutations in the leptin-melanocortin pathway (LMP) had significantly worse outcomes, maintaining only 4.9% total body weight loss [TBWL] over 15 years compared to up to 24.8% in other genetic groups,” Phenomix Sciences Co-founder Andres Acosta, MD, PhD, told GI & Hepatology News.

The study included details on the score’s development and predictive capability. It was presented at Digestive Disease Week^® (DDW) 2025

‘More Precise Bariatric Care’

The researchers recently developed a machine learning-assisted gene risk score for calories to satiation (CTSGRS), which mainly involves genes in the LMP. To assess the role of the score with or without LMP gene variants on weight loss and weight recurrence after RYGB, they identified 707 patients with a history of bariatric procedures from the Mayo Clinic Biobank. Patients with duodenal switch, revisional procedures, or who used antiobesity medications or became pregnant during follow-up were excluded.

To make predictions for 442 of the patients, the team first collected anthropometric data up to 15 years after RYGB. Then they used a two-step approach: Assessing for monogenic variants in the LMP and defining participants as carriers (LMP+) or noncarriers (LMP-). Then they defined the gene risk score (CTSGRS+ or CTSGRS-).

The result was four groups: LMP+/CTSGRS+, LMP+/CTSGRS-, LMP-/CTSGRS+, and LMP-/CTSGRS-. Multiple regression analysis was used to analyze TBWL percentage (TBWL%) between the groups at different timepoints, adjusting for baseline weight, age, and gender.

At the 10-year follow-up, the LMP+/CTSGRS+ group demonstrated a significantly higher weight recurrence (regain) of TBW% compared to the other groups.

At 15 years post-RYGB, the mean TBWL% for LMP+/CTSGRS+ was -4.9 vs -20.3 for LMP+/CTSGRS-, -18.0 for LMP-/CTSGRS+, and -24.8 for LMP-/CTSGRS-.

Further analyses showed that the LMP+/CTSGRS+ group had significantly less weight loss than LMP+/CTSGRS- and LMP-/CTSGRS- groups.

Based on the findings, the authors wrote, “Genotyping patients could improve the implementation of individualized weight-loss interventions, enhance weight-loss outcomes, and/or may explain one of the etiological factors associated with weight recurrence after RYGB.”

Acosta noted, “We’re actively expanding our research to include more diverse populations by age, sex, and race. This includes ongoing analysis to understand whether certain demographic or physiological characteristics affect how the test performs, particularly in the context of bariatric surgery.”

The team also is investigating the benefits of phenotyping for obesity comorbidities such as heart disease and diabetes, he said, and exploring whether early interventions in high-risk patients can prevent long-term weight regain and improve outcomes.

In addition, Acosta said, the team recently launched “the first prospective, placebo-controlled clinical trial using the MyPhenome test to predict response to semaglutide.” That study is based on earlier findings showing that patients identified with a Hungry Gut phenotype lost nearly twice as much weight on semaglutide compared with those who tested negative.

Overall, he concluded, “These findings open the door to more precise bariatric care. When we understand a patient’s biological drivers of obesity, we can make better decisions about the right procedure, follow-up, and long-term support. This moves us away from a one-size-fits-all model to care rooted in each patient’s unique biology.”

 

Potentially Paradigm-Shifting

Onur Kutlu, MD, associate professor of surgery and director of the Metabolic Surgery and Metabolic Health Program at the Miller School of Medicine, University of Miami, in Miami, Florida, commented on the study for GI & Hepatology News. “By integrating polygenic risk scores into predictive models, the authors offer an innovative method for identifying patients at elevated risk for weight regain following RYGB.”

“Their findings support the hypothesis that genetic predisposition — particularly involving energy homeostasis pathways — may underlie differential postoperative trajectories,” he said. “This approach has the potential to shift the paradigm from reactive to proactive management of weight recurrence.”

Because current options for treat weight regain are “suboptimal,” he said, “prevention becomes paramount. Preoperative identification of high-risk individuals could inform surgical decision-making, enable earlier interventions, and facilitate personalized postoperative monitoring and support.”

“If validated in larger, prospective cohorts, genetic risk stratification could enhance the precision of bariatric care and improve long-term outcomes,” he added. “Future studies should aim to validate these genetic models across diverse populations and explore how integration of behavioral, psychological, and genetic data may further refine patient selection and care pathways.”

The study was funded by Mayo Clinic and Phenomix Sciences. Gila Therapeutics and Phenomix Sciences licensed Acosta’s research technologies from the University of Florida and Mayo Clinic. Acosta declared receiving consultant fees in the past 5 years from Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, BI, Currax, Nestle, Phenomix Sciences, Bausch Health, and RareDiseases, as well as funding support from the National Institutes of Health, Vivus Pharmaceuticals, Novo Nordisk, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical, and Rhythm Pharmaceuticals. Kutlu declared having no conflicts of interest.

A version of this article appeared on Medscape.com.

Research on cannabis use disorder (CUD) has mainly focused on individuals aged < 65 years, but a recently published study in JAMA Network Open found one-third of older veterans who had used cannabis in the previous 30 days screened positive for CUD.

The cross-sectional study of 4503 veterans aged 65 to 84 years from the US Department of Veterans Affairs (VA) Cannabis and Aging Cohort found 57% of participants reported lifetime cannabis use, with 29% citing medical reasons, usually for pain management. About 10% reported using cannabis in the previous 30 days, with 52% reporting use for ≥ 20 days in a month. The odds of CUD were higher among men, respondents aged < 76 years, individuals with anxiety, and individuals who reported any illicit drug use or frequent cannabis use.

In 2019, 9.8% of veterans reported using cannabis in the previous year. In 2019 to 2020, > 20% of veterans aged 18 to 44 years said they had used cannabis in the previous 6 months. According to VA Health Systems Research, about 1 in 11 veterans had used cannabis in the previous year. Compared to the general US population, recent cannabis use was similar or slightly lower among veterans. Among those with previous year use, however, the percentage of veterans using cannabis for medical purposes was more than double that of the general population.

Older veterans are particularly at risk for CUD. Cannabis use can increase the chance of neuropsychiatric disorders, respiratory symptoms, and cardiovascular outcomes—all leading causes of death in older adults. They also have an elevated risk of suicidal ideation and therefore may be particularly susceptible to adverse effects of cannabis, even if used for therapeutic purposes.

In addition to CUD, older veterans may be at risk for tetrahydrocannabinol (THC) intoxication if they are unable to tolerate cannabis potency or the latent THC components found in products marketed as only having cannabidiol. THC is the primary psychoactive compound found in the cannabis plant and interacts with brain cannabinoid receptors to affect mood, perception, and various bodily functions. Cannabis potency has increased from about 3% in the 1980s to about 15% in recent years; the average THC-to-CBD ratio has increased substantially over the past decade.

Unlike veterans aged 18 to 25 years, those aged ≥ 65 years are less likely to use recreational cannabis, are more likely to use medicinal cannabis recommended by a health care professional, and report use for pain management, insomnia, and mental health (including posttraumatic stress disorder [PTSD]). Some research indicates that rates of cannabis use and CUD are particularly elevated among veterans with PTSD and major depressive disorder who may use cannabis as a means of coping with negative affect and sleep disturbances. PTSD is recognized as a qualifying condition by states that have legalized medicinal cannabis. 

Sleep disturbance, especially in conjunction with PTSD, is associated with CUD among veterans. According to the VA, research does not support cannabis as an effective PTSD treatment, a reason the 2023 VA/DoD Clinical Practice Guideline for PTSD does not recommend it for that use. In 2020, lifetime prevalence of CUD among veterans was 9.2%; the prevalence of past-6-month CUD diagnoses among veterans was 2.7%. Among veterans with PTSD, however, CUD rates were much higher (12.1%).

Current VA guidelines recommend that patients with CUD be offered referral to mental health services for evidence-based treatments, including motivational interviews, contingency management, and cognitive behavioral therapy. The JAMA Network Open study notes the importance of screening and informing older veterans about the risks of cannabis use: “Unidentified, patients cannot be offered existing evidence-based treatments. Despite increasing cannabis use among older adults, there is an inadequate evidence base on therapeutic benefits and potential harms from cannabis use among older people.”

Research on cannabis use disorder (CUD) has mainly focused on individuals aged < 65 years, but a recently published study in JAMA Network Open found one-third of older veterans who had used cannabis in the previous 30 days screened positive for CUD.

The cross-sectional study of 4503 veterans aged 65 to 84 years from the US Department of Veterans Affairs (VA) Cannabis and Aging Cohort found 57% of participants reported lifetime cannabis use, with 29% citing medical reasons, usually for pain management. About 10% reported using cannabis in the previous 30 days, with 52% reporting use for ≥ 20 days in a month. The odds of CUD were higher among men, respondents aged < 76 years, individuals with anxiety, and individuals who reported any illicit drug use or frequent cannabis use.

In 2019, 9.8% of veterans reported using cannabis in the previous year. In 2019 to 2020, > 20% of veterans aged 18 to 44 years said they had used cannabis in the previous 6 months. According to VA Health Systems Research, about 1 in 11 veterans had used cannabis in the previous year. Compared to the general US population, recent cannabis use was similar or slightly lower among veterans. Among those with previous year use, however, the percentage of veterans using cannabis for medical purposes was more than double that of the general population.

Older veterans are particularly at risk for CUD. Cannabis use can increase the chance of neuropsychiatric disorders, respiratory symptoms, and cardiovascular outcomes—all leading causes of death in older adults. They also have an elevated risk of suicidal ideation and therefore may be particularly susceptible to adverse effects of cannabis, even if used for therapeutic purposes.

In addition to CUD, older veterans may be at risk for tetrahydrocannabinol (THC) intoxication if they are unable to tolerate cannabis potency or the latent THC components found in products marketed as only having cannabidiol. THC is the primary psychoactive compound found in the cannabis plant and interacts with brain cannabinoid receptors to affect mood, perception, and various bodily functions. Cannabis potency has increased from about 3% in the 1980s to about 15% in recent years; the average THC-to-CBD ratio has increased substantially over the past decade.

Unlike veterans aged 18 to 25 years, those aged ≥ 65 years are less likely to use recreational cannabis, are more likely to use medicinal cannabis recommended by a health care professional, and report use for pain management, insomnia, and mental health (including posttraumatic stress disorder [PTSD]). Some research indicates that rates of cannabis use and CUD are particularly elevated among veterans with PTSD and major depressive disorder who may use cannabis as a means of coping with negative affect and sleep disturbances. PTSD is recognized as a qualifying condition by states that have legalized medicinal cannabis. 

Sleep disturbance, especially in conjunction with PTSD, is associated with CUD among veterans. According to the VA, research does not support cannabis as an effective PTSD treatment, a reason the 2023 VA/DoD Clinical Practice Guideline for PTSD does not recommend it for that use. In 2020, lifetime prevalence of CUD among veterans was 9.2%; the prevalence of past-6-month CUD diagnoses among veterans was 2.7%. Among veterans with PTSD, however, CUD rates were much higher (12.1%).

Current VA guidelines recommend that patients with CUD be offered referral to mental health services for evidence-based treatments, including motivational interviews, contingency management, and cognitive behavioral therapy. The JAMA Network Open study notes the importance of screening and informing older veterans about the risks of cannabis use: “Unidentified, patients cannot be offered existing evidence-based treatments. Despite increasing cannabis use among older adults, there is an inadequate evidence base on therapeutic benefits and potential harms from cannabis use among older people.”

Research on cannabis use disorder (CUD) has mainly focused on individuals aged < 65 years, but a recently published study in JAMA Network Open found one-third of older veterans who had used cannabis in the previous 30 days screened positive for CUD.

The cross-sectional study of 4503 veterans aged 65 to 84 years from the US Department of Veterans Affairs (VA) Cannabis and Aging Cohort found 57% of participants reported lifetime cannabis use, with 29% citing medical reasons, usually for pain management. About 10% reported using cannabis in the previous 30 days, with 52% reporting use for ≥ 20 days in a month. The odds of CUD were higher among men, respondents aged < 76 years, individuals with anxiety, and individuals who reported any illicit drug use or frequent cannabis use.

In 2019, 9.8% of veterans reported using cannabis in the previous year. In 2019 to 2020, > 20% of veterans aged 18 to 44 years said they had used cannabis in the previous 6 months. According to VA Health Systems Research, about 1 in 11 veterans had used cannabis in the previous year. Compared to the general US population, recent cannabis use was similar or slightly lower among veterans. Among those with previous year use, however, the percentage of veterans using cannabis for medical purposes was more than double that of the general population.

Older veterans are particularly at risk for CUD. Cannabis use can increase the chance of neuropsychiatric disorders, respiratory symptoms, and cardiovascular outcomes—all leading causes of death in older adults. They also have an elevated risk of suicidal ideation and therefore may be particularly susceptible to adverse effects of cannabis, even if used for therapeutic purposes.

In addition to CUD, older veterans may be at risk for tetrahydrocannabinol (THC) intoxication if they are unable to tolerate cannabis potency or the latent THC components found in products marketed as only having cannabidiol. THC is the primary psychoactive compound found in the cannabis plant and interacts with brain cannabinoid receptors to affect mood, perception, and various bodily functions. Cannabis potency has increased from about 3% in the 1980s to about 15% in recent years; the average THC-to-CBD ratio has increased substantially over the past decade.

Unlike veterans aged 18 to 25 years, those aged ≥ 65 years are less likely to use recreational cannabis, are more likely to use medicinal cannabis recommended by a health care professional, and report use for pain management, insomnia, and mental health (including posttraumatic stress disorder [PTSD]). Some research indicates that rates of cannabis use and CUD are particularly elevated among veterans with PTSD and major depressive disorder who may use cannabis as a means of coping with negative affect and sleep disturbances. PTSD is recognized as a qualifying condition by states that have legalized medicinal cannabis. 

Sleep disturbance, especially in conjunction with PTSD, is associated with CUD among veterans. According to the VA, research does not support cannabis as an effective PTSD treatment, a reason the 2023 VA/DoD Clinical Practice Guideline for PTSD does not recommend it for that use. In 2020, lifetime prevalence of CUD among veterans was 9.2%; the prevalence of past-6-month CUD diagnoses among veterans was 2.7%. Among veterans with PTSD, however, CUD rates were much higher (12.1%).

Current VA guidelines recommend that patients with CUD be offered referral to mental health services for evidence-based treatments, including motivational interviews, contingency management, and cognitive behavioral therapy. The JAMA Network Open study notes the importance of screening and informing older veterans about the risks of cannabis use: “Unidentified, patients cannot be offered existing evidence-based treatments. Despite increasing cannabis use among older adults, there is an inadequate evidence base on therapeutic benefits and potential harms from cannabis use among older people.”

Adding the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib to abiraterone acetate plus prednisone delayed disease progression and postponed the onset of symptoms in patients with metastatic castration-sensitive prostate cancer with homologous recombination repair (HRR) genetic alterations, according to findings from the AMPLITUDE trial.

An interim analysis also demonstrated an early trend toward improved overall survival in patients who received niraparib.

These findings support adding niraparib to abiraterone acetate plus prednisone “as a new treatment option” in patients with HRR alterations, said Study Chief Gerhardt Attard, MD, PhD, chair of medical oncology, University College London Cancer Institute, London, England, speaking at the American Society of Clinical Oncology (ASCO) 2025 annual meeting.

The findings also highlight that “it’s going to be incredibly important that patients who get diagnosed with hormone-sensitive prostate cancer are tested to see if they have these mutations, so they can be offered the right therapy at the right time,” Outside Expert Bradley McGregor, MD, with Dana-Farber Cancer Institute in Boston, said during a press briefing.

Ultimately, “you don’t know if you don’t test,” McGregor added.

About one quarter of patients with metastatic castration-sensitive prostate cancer have alterations in HRR genes, about half of which are BRCA mutations. These patients typically experience faster disease progression and worse outcomes. An androgen receptor pathway inhibitor, such as abiraterone, alongside androgen deprivation therapy with or without docetaxel, is standard therapy for these patients, but “there is still a need for treatments that are tailored to patients whose tumors harbor HRR alterations,” Attard said in a press release.

Adding niraparib to this standard regimen could help improve survival in these patients.

In 2023, the FDA approved niraparib and abiraterone acetate to treat BRCA-mutated metastatic castration-resistant prostate cancer, after findings from the MAGNITUDE study demonstrated improved progression-free survival (PFS).

The phase 3 AMPLITUDE trial set out to evaluate whether this combination would yield similar survival benefits in metastatic castration-sensitive prostate cancer with HRR mutations.

In the study, 696 patients (median age, 68 years) with metastatic castration-sensitive prostate cancer and one or more HRR gene alterations were randomly allocated (1:1) to niraparib with abiraterone acetate plus prednisone or placebo with abiraterone acetate plus prednisone.

Exclusion criteria included any prior PARP inhibitor therapy or androgen receptor pathway inhibitor other than abiraterone. Eligible patients could have received at most 6 months of androgen deprivation therapy, ≤ 6 cycles of docetaxel, ≤ 45 days of abiraterone acetate plus prednisone and palliative radiation.

Baseline characteristics were well balanced between the groups. Just over half the patients in each group had BRCA1 or BRCA2 alterations. The majority had an electrocorticogram performance status of 0, but high-risk features with a predominance for synchronous metastatic disease and metastatic high volume. About 16% had received prior docetaxel, in keeping with real world data, Attard noted.

At a median follow-up of 30.8 months, niraparib plus standard therapy led to a significant 37% reduction in the risk for radiographic progression or death. The median radiographic PFS (rPFS) was not reached in the niraparib group vs 29.5 months in the placebo group (hazard ratio [HR], 0.63; P = .0001).

Patients with BRCA alterations, in particular, showed the greatest benefit, with niraparib reducing the risk for radiographic progression or death by 48% compared to placebo (median rPFS not reached vs 26 months; HR, 0.52; P < .0001).

On the key secondary endpoint of time to symptomatic progression, adding niraparib led to a “statistically and clinically” significant benefit — a 50% lower in the risk for symptomatic progression in the full population (HR, 0.50), and a 56% lower risk in BRCA-mutant group (HR, 0.44).

The first interim analysis also showed an early trend toward improved overall survival favoring the niraparib combination, with a reduction in the risk for death of 21% in the HRR-mutant population (HR, 0.79; P = .10) and 25% (HR, 0.75; P = .15) in the BRCA-mutant population.

Grade 3/4 adverse events were more common with the niraparib combination group compared to the placebo group (75% vs 59%), with anemia and hypertension being the most common. However, treatment discontinuations due to adverse remained low (15% with niraparib vs 10% with placebo).

Attard noted, however, that half the target number of patients required for the final analysis died. Still, “in my view, there’s a clear trend for favoring survival in the patients randomized to niraparib,” he told attendees.

 

‘Exciting News’ for Patients 

The AMPLITUDE results are “really exciting news for our patients,” McGregor said.

Considering the poor prognosis of patients with metastatic castration-sensitive prostate cancer, “it is reasonable to prioritize early access to PARP inhibitors for these men, at least for the ones with BRCA mutations,” added ASCO discussant Joaquin Mateo, MD, PhD, with Vall d’Hebron Institute of Oncology, Barcelona, Spain.

However, Mateo explained, “I think that for patients with mutations in the other genes, I will be more prudent, and I’ll be on the lookout for the overall survival data to mature.”

The other key conclusion, Mateo said, is that genomic profiling “should be moved earlier into the patient course, and I am confident that embedding genomic profiling into the diagnostic evaluations of metastatic prostate cancer is also going to result in better quality of testing, more efficacious testing, and also a more equitable framework of access to testing for patients.”



This study was funded by Janssen Research & Development, LLC. Attard and Mateo disclosed relationships with Janssen and other pharmaceutical companies. McGregor disclosed relationships with Arcus Biosciences, Astellas, AVEO, Bristol Myers Squibb, Daiichi Sankyo, AstraZeneca, and other companies.

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

Adding the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib to abiraterone acetate plus prednisone delayed disease progression and postponed the onset of symptoms in patients with metastatic castration-sensitive prostate cancer with homologous recombination repair (HRR) genetic alterations, according to findings from the AMPLITUDE trial.

An interim analysis also demonstrated an early trend toward improved overall survival in patients who received niraparib.

These findings support adding niraparib to abiraterone acetate plus prednisone “as a new treatment option” in patients with HRR alterations, said Study Chief Gerhardt Attard, MD, PhD, chair of medical oncology, University College London Cancer Institute, London, England, speaking at the American Society of Clinical Oncology (ASCO) 2025 annual meeting.

The findings also highlight that “it’s going to be incredibly important that patients who get diagnosed with hormone-sensitive prostate cancer are tested to see if they have these mutations, so they can be offered the right therapy at the right time,” Outside Expert Bradley McGregor, MD, with Dana-Farber Cancer Institute in Boston, said during a press briefing.

Ultimately, “you don’t know if you don’t test,” McGregor added.

About one quarter of patients with metastatic castration-sensitive prostate cancer have alterations in HRR genes, about half of which are BRCA mutations. These patients typically experience faster disease progression and worse outcomes. An androgen receptor pathway inhibitor, such as abiraterone, alongside androgen deprivation therapy with or without docetaxel, is standard therapy for these patients, but “there is still a need for treatments that are tailored to patients whose tumors harbor HRR alterations,” Attard said in a press release.

Adding niraparib to this standard regimen could help improve survival in these patients.

In 2023, the FDA approved niraparib and abiraterone acetate to treat BRCA-mutated metastatic castration-resistant prostate cancer, after findings from the MAGNITUDE study demonstrated improved progression-free survival (PFS).

The phase 3 AMPLITUDE trial set out to evaluate whether this combination would yield similar survival benefits in metastatic castration-sensitive prostate cancer with HRR mutations.

In the study, 696 patients (median age, 68 years) with metastatic castration-sensitive prostate cancer and one or more HRR gene alterations were randomly allocated (1:1) to niraparib with abiraterone acetate plus prednisone or placebo with abiraterone acetate plus prednisone.

Exclusion criteria included any prior PARP inhibitor therapy or androgen receptor pathway inhibitor other than abiraterone. Eligible patients could have received at most 6 months of androgen deprivation therapy, ≤ 6 cycles of docetaxel, ≤ 45 days of abiraterone acetate plus prednisone and palliative radiation.

Baseline characteristics were well balanced between the groups. Just over half the patients in each group had BRCA1 or BRCA2 alterations. The majority had an electrocorticogram performance status of 0, but high-risk features with a predominance for synchronous metastatic disease and metastatic high volume. About 16% had received prior docetaxel, in keeping with real world data, Attard noted.

At a median follow-up of 30.8 months, niraparib plus standard therapy led to a significant 37% reduction in the risk for radiographic progression or death. The median radiographic PFS (rPFS) was not reached in the niraparib group vs 29.5 months in the placebo group (hazard ratio [HR], 0.63; P = .0001).

Patients with BRCA alterations, in particular, showed the greatest benefit, with niraparib reducing the risk for radiographic progression or death by 48% compared to placebo (median rPFS not reached vs 26 months; HR, 0.52; P < .0001).

On the key secondary endpoint of time to symptomatic progression, adding niraparib led to a “statistically and clinically” significant benefit — a 50% lower in the risk for symptomatic progression in the full population (HR, 0.50), and a 56% lower risk in BRCA-mutant group (HR, 0.44).

The first interim analysis also showed an early trend toward improved overall survival favoring the niraparib combination, with a reduction in the risk for death of 21% in the HRR-mutant population (HR, 0.79; P = .10) and 25% (HR, 0.75; P = .15) in the BRCA-mutant population.

Grade 3/4 adverse events were more common with the niraparib combination group compared to the placebo group (75% vs 59%), with anemia and hypertension being the most common. However, treatment discontinuations due to adverse remained low (15% with niraparib vs 10% with placebo).

Attard noted, however, that half the target number of patients required for the final analysis died. Still, “in my view, there’s a clear trend for favoring survival in the patients randomized to niraparib,” he told attendees.

 

‘Exciting News’ for Patients 

The AMPLITUDE results are “really exciting news for our patients,” McGregor said.

Considering the poor prognosis of patients with metastatic castration-sensitive prostate cancer, “it is reasonable to prioritize early access to PARP inhibitors for these men, at least for the ones with BRCA mutations,” added ASCO discussant Joaquin Mateo, MD, PhD, with Vall d’Hebron Institute of Oncology, Barcelona, Spain.

However, Mateo explained, “I think that for patients with mutations in the other genes, I will be more prudent, and I’ll be on the lookout for the overall survival data to mature.”

The other key conclusion, Mateo said, is that genomic profiling “should be moved earlier into the patient course, and I am confident that embedding genomic profiling into the diagnostic evaluations of metastatic prostate cancer is also going to result in better quality of testing, more efficacious testing, and also a more equitable framework of access to testing for patients.”



This study was funded by Janssen Research & Development, LLC. Attard and Mateo disclosed relationships with Janssen and other pharmaceutical companies. McGregor disclosed relationships with Arcus Biosciences, Astellas, AVEO, Bristol Myers Squibb, Daiichi Sankyo, AstraZeneca, and other companies.

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

Adding the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib to abiraterone acetate plus prednisone delayed disease progression and postponed the onset of symptoms in patients with metastatic castration-sensitive prostate cancer with homologous recombination repair (HRR) genetic alterations, according to findings from the AMPLITUDE trial.

An interim analysis also demonstrated an early trend toward improved overall survival in patients who received niraparib.

These findings support adding niraparib to abiraterone acetate plus prednisone “as a new treatment option” in patients with HRR alterations, said Study Chief Gerhardt Attard, MD, PhD, chair of medical oncology, University College London Cancer Institute, London, England, speaking at the American Society of Clinical Oncology (ASCO) 2025 annual meeting.

The findings also highlight that “it’s going to be incredibly important that patients who get diagnosed with hormone-sensitive prostate cancer are tested to see if they have these mutations, so they can be offered the right therapy at the right time,” Outside Expert Bradley McGregor, MD, with Dana-Farber Cancer Institute in Boston, said during a press briefing.

Ultimately, “you don’t know if you don’t test,” McGregor added.

About one quarter of patients with metastatic castration-sensitive prostate cancer have alterations in HRR genes, about half of which are BRCA mutations. These patients typically experience faster disease progression and worse outcomes. An androgen receptor pathway inhibitor, such as abiraterone, alongside androgen deprivation therapy with or without docetaxel, is standard therapy for these patients, but “there is still a need for treatments that are tailored to patients whose tumors harbor HRR alterations,” Attard said in a press release.

Adding niraparib to this standard regimen could help improve survival in these patients.

In 2023, the FDA approved niraparib and abiraterone acetate to treat BRCA-mutated metastatic castration-resistant prostate cancer, after findings from the MAGNITUDE study demonstrated improved progression-free survival (PFS).

The phase 3 AMPLITUDE trial set out to evaluate whether this combination would yield similar survival benefits in metastatic castration-sensitive prostate cancer with HRR mutations.

In the study, 696 patients (median age, 68 years) with metastatic castration-sensitive prostate cancer and one or more HRR gene alterations were randomly allocated (1:1) to niraparib with abiraterone acetate plus prednisone or placebo with abiraterone acetate plus prednisone.

Exclusion criteria included any prior PARP inhibitor therapy or androgen receptor pathway inhibitor other than abiraterone. Eligible patients could have received at most 6 months of androgen deprivation therapy, ≤ 6 cycles of docetaxel, ≤ 45 days of abiraterone acetate plus prednisone and palliative radiation.

Baseline characteristics were well balanced between the groups. Just over half the patients in each group had BRCA1 or BRCA2 alterations. The majority had an electrocorticogram performance status of 0, but high-risk features with a predominance for synchronous metastatic disease and metastatic high volume. About 16% had received prior docetaxel, in keeping with real world data, Attard noted.

At a median follow-up of 30.8 months, niraparib plus standard therapy led to a significant 37% reduction in the risk for radiographic progression or death. The median radiographic PFS (rPFS) was not reached in the niraparib group vs 29.5 months in the placebo group (hazard ratio [HR], 0.63; P = .0001).

Patients with BRCA alterations, in particular, showed the greatest benefit, with niraparib reducing the risk for radiographic progression or death by 48% compared to placebo (median rPFS not reached vs 26 months; HR, 0.52; P < .0001).

On the key secondary endpoint of time to symptomatic progression, adding niraparib led to a “statistically and clinically” significant benefit — a 50% lower in the risk for symptomatic progression in the full population (HR, 0.50), and a 56% lower risk in BRCA-mutant group (HR, 0.44).

The first interim analysis also showed an early trend toward improved overall survival favoring the niraparib combination, with a reduction in the risk for death of 21% in the HRR-mutant population (HR, 0.79; P = .10) and 25% (HR, 0.75; P = .15) in the BRCA-mutant population.

Grade 3/4 adverse events were more common with the niraparib combination group compared to the placebo group (75% vs 59%), with anemia and hypertension being the most common. However, treatment discontinuations due to adverse remained low (15% with niraparib vs 10% with placebo).

Attard noted, however, that half the target number of patients required for the final analysis died. Still, “in my view, there’s a clear trend for favoring survival in the patients randomized to niraparib,” he told attendees.

 

‘Exciting News’ for Patients 

The AMPLITUDE results are “really exciting news for our patients,” McGregor said.

Considering the poor prognosis of patients with metastatic castration-sensitive prostate cancer, “it is reasonable to prioritize early access to PARP inhibitors for these men, at least for the ones with BRCA mutations,” added ASCO discussant Joaquin Mateo, MD, PhD, with Vall d’Hebron Institute of Oncology, Barcelona, Spain.

However, Mateo explained, “I think that for patients with mutations in the other genes, I will be more prudent, and I’ll be on the lookout for the overall survival data to mature.”

The other key conclusion, Mateo said, is that genomic profiling “should be moved earlier into the patient course, and I am confident that embedding genomic profiling into the diagnostic evaluations of metastatic prostate cancer is also going to result in better quality of testing, more efficacious testing, and also a more equitable framework of access to testing for patients.”



This study was funded by Janssen Research & Development, LLC. Attard and Mateo disclosed relationships with Janssen and other pharmaceutical companies. McGregor disclosed relationships with Arcus Biosciences, Astellas, AVEO, Bristol Myers Squibb, Daiichi Sankyo, AstraZeneca, and other companies.

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

A new combination modality demonstrated excellent sensitivity and negative predictive value compared with endoscopy in a prospective study of at-risk veterans screened for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC), a small comparative study in US veterans found.

BE is up to three times more prevalent in veterans than in the general population.

This and other minimally invasive approaches may reduce patient anxiety and increase screening rates, according to investigators led by Katarina B. Greer, MD, MS, of the VA Northeast Ohio Healthcare System and Case Western University in Cleveland. Such screening platforms are expected to open a window on improved prognosis for EAC by offering well-tolerated, office-based testing, the authors wrote in The American Journal of Gastroenterology.

Greer and colleagues compared standard upper endoscopy with EsoCheck (EC), a nonendoscopic esophageal balloon cell-sampling device coupled with EsoGuard (EG), a DNA-based precancer screening assay, with standard upper endoscopy, an FDA-approved minimally invasive alternative.

Sensitivity and specificity of combined EC/EG for esophagogastroduodenoscopy (EGD)-detected BE/EAC were 92.9% (95% CI, 66.1-99.8) and 72.2% (95% CI, 62.1-80.8), respectively. Positive and negative predictive values were 32.5% (95% CI, 18.6-49.1) and 98.6% (95% CI, 92.4-100), respectively.

“With its strong negative predictive power, this screening modality could be a first-line tool available to a greater number of patients,” Greer and associates wrote. “Data from this test support the notion that EC could be performed as a triaging test to increase the yield of diagnostic upper endoscopy 2.5-fold.”

The US rates of EAC have increased more than six-fold in the past four decades and continue to rise. In 2023, 21,560 cases of EAC were diagnosed here. The prognosis for EAC is still poor, with fewer than 22% of patients surviving beyond 5 years.

Current guidelines recommend sedated EGD for patients with chronic gastroesophageal reflux disease (GERD) and additional BE risk factors such as smoking, obesity, and family history. This strategy, however, often fails to detect BE when symptoms are well controlled with over-the-counter or physician-prescribed therapies, Greer and colleagues noted. It also fails to detect BE in individuals without GERD, who comprise 40% of those who develop EAC.

Fewer than 5% of EACs are diagnosed as early-stage lesions caught by surveillance of patients with previously detected BE.

 

Study Details

The researchers recruited veterans meeting American College of Gastroenterology criteria for endoscopic BE and EAC screening at the Louis Stokes Cleveland Veterans Affairs Medical Center.

Of 782 eligible veterans, 130 (16.6%) entered the study and 124 completed screening. Common reasons for nonparticipation included completion of upper endoscopy outside of the VA healthcare system, lack of interest in joining a research study, and no recommendation for screening from referring gastroenterology or primary care providers. Eligible candidates had gastroesophageal reflux disorder plus three additional risk factors, such as smoking, higher BMI, male sex, age 50 years or older, and family history. The mean number of risk factors was 4.1.

“Available data suggest that family history is the strongest predictor of BE diagnosis, as prevalence of BE among those with family history was 23%,” Greer’s group wrote. “This points to high priority of pursuing screening in patients with family history of the condition, followed by patients who share multiple risk factors.”

All participants completed unsedated EC-guided distal esophageal sampling followed by a sedated EGD on the same day. The prevalence of BE/EAC was 12.9% (n = 14/2), based on standard EGD.

“The study was not powered to prospectively determine EC diagnostic accuracy for subgroups of nondysplastic and dysplastic BE and EAC. These data are reported for this device in development studies but not available for our study population,” the authors wrote. In comparison, they noted, the Cytosponge-TFF3, another nonendoscopic screening device for EAC and BE, exhibited lower sensitivity of 79.5%-87.2%, depending on lesion length, but higher specificity of 92.4%.

 

Procedural Anxiety

Baseline scores on the short-form six-item Spielberger State-Trait Anxiety Inventory-6 (STAI-6) revealed notable levels of periprocedural anxiety. STAI-6 scores range from 20 to 80, with higher scores indicating more severe anxiety. In the VA study, scores ranged from 20 to 60, and most domains constituting the scores were the same before and after the procedure. Participants did, however, report a statistically significant decrease in sense of worry after EC and reported good tolerability for both EC and EG.

Offering an outsider’s perspective on the study, Joshua Sloan, DO, an esophageal gastroenterologist at University of Minnesota Medical Center in Minneapolis, said that with the acceleration of US rates of EAC, developing a nonendoscopic screening tool to improve identification of Barrett’s and perhaps early EAC is important. “The study by Greer et al helps support the use of nonendoscopic screening with EsoCheck and EsoGuard to identify these conditions,” he told GI & Hepatology News. “It will be interesting to see similar studies in the non-VA population as well. As the study notes, veterans are an enriched population with a higher prevalence of Barrett’s esophagus.”

Ultimately, Sloan added, “the hope is to increase our ability to identify and manage BE before it becomes EAC. Nonendoscopic screening tools have the potential to increase diagnosis and funnel the appropriate patients for endoscopic surveillance.”

 

The Bottom Line 

“Calculations regarding effectiveness of the two-step screening strategy afforded by EC indicate that the burden of screening would be reduced by at least half (53%),” the authors wrote. Since the estimated size of the US screen-eligible population ranges from 19.7 million to 120.1 million, noninvasive tools could significantly decrease EGD procedures. A formal cost effectiveness analysis is being conducted and will be published separately.

This study was funded by a Department of Defense award.

Co-Author Chak reported device patents assigned to Case Western Reserve University and licensed to Lucid Diagnostics. The other authors had no competing interests to declare. Sloan disclosed speaking and/or advisory work for Sanofi-Regeneron, Phathom Pharmaceuticals, and Takeda Pharmaceuticals unrelated to his comments.

A version of this article appeared on Medscape.com.

A new combination modality demonstrated excellent sensitivity and negative predictive value compared with endoscopy in a prospective study of at-risk veterans screened for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC), a small comparative study in US veterans found.

BE is up to three times more prevalent in veterans than in the general population.

This and other minimally invasive approaches may reduce patient anxiety and increase screening rates, according to investigators led by Katarina B. Greer, MD, MS, of the VA Northeast Ohio Healthcare System and Case Western University in Cleveland. Such screening platforms are expected to open a window on improved prognosis for EAC by offering well-tolerated, office-based testing, the authors wrote in The American Journal of Gastroenterology.

Greer and colleagues compared standard upper endoscopy with EsoCheck (EC), a nonendoscopic esophageal balloon cell-sampling device coupled with EsoGuard (EG), a DNA-based precancer screening assay, with standard upper endoscopy, an FDA-approved minimally invasive alternative.

Sensitivity and specificity of combined EC/EG for esophagogastroduodenoscopy (EGD)-detected BE/EAC were 92.9% (95% CI, 66.1-99.8) and 72.2% (95% CI, 62.1-80.8), respectively. Positive and negative predictive values were 32.5% (95% CI, 18.6-49.1) and 98.6% (95% CI, 92.4-100), respectively.

“With its strong negative predictive power, this screening modality could be a first-line tool available to a greater number of patients,” Greer and associates wrote. “Data from this test support the notion that EC could be performed as a triaging test to increase the yield of diagnostic upper endoscopy 2.5-fold.”

The US rates of EAC have increased more than six-fold in the past four decades and continue to rise. In 2023, 21,560 cases of EAC were diagnosed here. The prognosis for EAC is still poor, with fewer than 22% of patients surviving beyond 5 years.

Current guidelines recommend sedated EGD for patients with chronic gastroesophageal reflux disease (GERD) and additional BE risk factors such as smoking, obesity, and family history. This strategy, however, often fails to detect BE when symptoms are well controlled with over-the-counter or physician-prescribed therapies, Greer and colleagues noted. It also fails to detect BE in individuals without GERD, who comprise 40% of those who develop EAC.

Fewer than 5% of EACs are diagnosed as early-stage lesions caught by surveillance of patients with previously detected BE.

 

Study Details

The researchers recruited veterans meeting American College of Gastroenterology criteria for endoscopic BE and EAC screening at the Louis Stokes Cleveland Veterans Affairs Medical Center.

Of 782 eligible veterans, 130 (16.6%) entered the study and 124 completed screening. Common reasons for nonparticipation included completion of upper endoscopy outside of the VA healthcare system, lack of interest in joining a research study, and no recommendation for screening from referring gastroenterology or primary care providers. Eligible candidates had gastroesophageal reflux disorder plus three additional risk factors, such as smoking, higher BMI, male sex, age 50 years or older, and family history. The mean number of risk factors was 4.1.

“Available data suggest that family history is the strongest predictor of BE diagnosis, as prevalence of BE among those with family history was 23%,” Greer’s group wrote. “This points to high priority of pursuing screening in patients with family history of the condition, followed by patients who share multiple risk factors.”

All participants completed unsedated EC-guided distal esophageal sampling followed by a sedated EGD on the same day. The prevalence of BE/EAC was 12.9% (n = 14/2), based on standard EGD.

“The study was not powered to prospectively determine EC diagnostic accuracy for subgroups of nondysplastic and dysplastic BE and EAC. These data are reported for this device in development studies but not available for our study population,” the authors wrote. In comparison, they noted, the Cytosponge-TFF3, another nonendoscopic screening device for EAC and BE, exhibited lower sensitivity of 79.5%-87.2%, depending on lesion length, but higher specificity of 92.4%.

 

Procedural Anxiety

Baseline scores on the short-form six-item Spielberger State-Trait Anxiety Inventory-6 (STAI-6) revealed notable levels of periprocedural anxiety. STAI-6 scores range from 20 to 80, with higher scores indicating more severe anxiety. In the VA study, scores ranged from 20 to 60, and most domains constituting the scores were the same before and after the procedure. Participants did, however, report a statistically significant decrease in sense of worry after EC and reported good tolerability for both EC and EG.

Offering an outsider’s perspective on the study, Joshua Sloan, DO, an esophageal gastroenterologist at University of Minnesota Medical Center in Minneapolis, said that with the acceleration of US rates of EAC, developing a nonendoscopic screening tool to improve identification of Barrett’s and perhaps early EAC is important. “The study by Greer et al helps support the use of nonendoscopic screening with EsoCheck and EsoGuard to identify these conditions,” he told GI & Hepatology News. “It will be interesting to see similar studies in the non-VA population as well. As the study notes, veterans are an enriched population with a higher prevalence of Barrett’s esophagus.”

Ultimately, Sloan added, “the hope is to increase our ability to identify and manage BE before it becomes EAC. Nonendoscopic screening tools have the potential to increase diagnosis and funnel the appropriate patients for endoscopic surveillance.”

 

The Bottom Line 

“Calculations regarding effectiveness of the two-step screening strategy afforded by EC indicate that the burden of screening would be reduced by at least half (53%),” the authors wrote. Since the estimated size of the US screen-eligible population ranges from 19.7 million to 120.1 million, noninvasive tools could significantly decrease EGD procedures. A formal cost effectiveness analysis is being conducted and will be published separately.

This study was funded by a Department of Defense award.

Co-Author Chak reported device patents assigned to Case Western Reserve University and licensed to Lucid Diagnostics. The other authors had no competing interests to declare. Sloan disclosed speaking and/or advisory work for Sanofi-Regeneron, Phathom Pharmaceuticals, and Takeda Pharmaceuticals unrelated to his comments.

A version of this article appeared on Medscape.com.

A new combination modality demonstrated excellent sensitivity and negative predictive value compared with endoscopy in a prospective study of at-risk veterans screened for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC), a small comparative study in US veterans found.

BE is up to three times more prevalent in veterans than in the general population.

This and other minimally invasive approaches may reduce patient anxiety and increase screening rates, according to investigators led by Katarina B. Greer, MD, MS, of the VA Northeast Ohio Healthcare System and Case Western University in Cleveland. Such screening platforms are expected to open a window on improved prognosis for EAC by offering well-tolerated, office-based testing, the authors wrote in The American Journal of Gastroenterology.

Greer and colleagues compared standard upper endoscopy with EsoCheck (EC), a nonendoscopic esophageal balloon cell-sampling device coupled with EsoGuard (EG), a DNA-based precancer screening assay, with standard upper endoscopy, an FDA-approved minimally invasive alternative.

Sensitivity and specificity of combined EC/EG for esophagogastroduodenoscopy (EGD)-detected BE/EAC were 92.9% (95% CI, 66.1-99.8) and 72.2% (95% CI, 62.1-80.8), respectively. Positive and negative predictive values were 32.5% (95% CI, 18.6-49.1) and 98.6% (95% CI, 92.4-100), respectively.

“With its strong negative predictive power, this screening modality could be a first-line tool available to a greater number of patients,” Greer and associates wrote. “Data from this test support the notion that EC could be performed as a triaging test to increase the yield of diagnostic upper endoscopy 2.5-fold.”

The US rates of EAC have increased more than six-fold in the past four decades and continue to rise. In 2023, 21,560 cases of EAC were diagnosed here. The prognosis for EAC is still poor, with fewer than 22% of patients surviving beyond 5 years.

Current guidelines recommend sedated EGD for patients with chronic gastroesophageal reflux disease (GERD) and additional BE risk factors such as smoking, obesity, and family history. This strategy, however, often fails to detect BE when symptoms are well controlled with over-the-counter or physician-prescribed therapies, Greer and colleagues noted. It also fails to detect BE in individuals without GERD, who comprise 40% of those who develop EAC.

Fewer than 5% of EACs are diagnosed as early-stage lesions caught by surveillance of patients with previously detected BE.

 

Study Details

The researchers recruited veterans meeting American College of Gastroenterology criteria for endoscopic BE and EAC screening at the Louis Stokes Cleveland Veterans Affairs Medical Center.

Of 782 eligible veterans, 130 (16.6%) entered the study and 124 completed screening. Common reasons for nonparticipation included completion of upper endoscopy outside of the VA healthcare system, lack of interest in joining a research study, and no recommendation for screening from referring gastroenterology or primary care providers. Eligible candidates had gastroesophageal reflux disorder plus three additional risk factors, such as smoking, higher BMI, male sex, age 50 years or older, and family history. The mean number of risk factors was 4.1.

“Available data suggest that family history is the strongest predictor of BE diagnosis, as prevalence of BE among those with family history was 23%,” Greer’s group wrote. “This points to high priority of pursuing screening in patients with family history of the condition, followed by patients who share multiple risk factors.”

All participants completed unsedated EC-guided distal esophageal sampling followed by a sedated EGD on the same day. The prevalence of BE/EAC was 12.9% (n = 14/2), based on standard EGD.

“The study was not powered to prospectively determine EC diagnostic accuracy for subgroups of nondysplastic and dysplastic BE and EAC. These data are reported for this device in development studies but not available for our study population,” the authors wrote. In comparison, they noted, the Cytosponge-TFF3, another nonendoscopic screening device for EAC and BE, exhibited lower sensitivity of 79.5%-87.2%, depending on lesion length, but higher specificity of 92.4%.

 

Procedural Anxiety

Baseline scores on the short-form six-item Spielberger State-Trait Anxiety Inventory-6 (STAI-6) revealed notable levels of periprocedural anxiety. STAI-6 scores range from 20 to 80, with higher scores indicating more severe anxiety. In the VA study, scores ranged from 20 to 60, and most domains constituting the scores were the same before and after the procedure. Participants did, however, report a statistically significant decrease in sense of worry after EC and reported good tolerability for both EC and EG.

Offering an outsider’s perspective on the study, Joshua Sloan, DO, an esophageal gastroenterologist at University of Minnesota Medical Center in Minneapolis, said that with the acceleration of US rates of EAC, developing a nonendoscopic screening tool to improve identification of Barrett’s and perhaps early EAC is important. “The study by Greer et al helps support the use of nonendoscopic screening with EsoCheck and EsoGuard to identify these conditions,” he told GI & Hepatology News. “It will be interesting to see similar studies in the non-VA population as well. As the study notes, veterans are an enriched population with a higher prevalence of Barrett’s esophagus.”

Ultimately, Sloan added, “the hope is to increase our ability to identify and manage BE before it becomes EAC. Nonendoscopic screening tools have the potential to increase diagnosis and funnel the appropriate patients for endoscopic surveillance.”

 

The Bottom Line 

“Calculations regarding effectiveness of the two-step screening strategy afforded by EC indicate that the burden of screening would be reduced by at least half (53%),” the authors wrote. Since the estimated size of the US screen-eligible population ranges from 19.7 million to 120.1 million, noninvasive tools could significantly decrease EGD procedures. A formal cost effectiveness analysis is being conducted and will be published separately.

This study was funded by a Department of Defense award.

Co-Author Chak reported device patents assigned to Case Western Reserve University and licensed to Lucid Diagnostics. The other authors had no competing interests to declare. Sloan disclosed speaking and/or advisory work for Sanofi-Regeneron, Phathom Pharmaceuticals, and Takeda Pharmaceuticals unrelated to his comments.

A version of this article appeared on Medscape.com.