TOPLINE:

Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for precancerous colorectal adenomatous polyps in men and women, according to results of a large study.

METHODOLOGY:

• Researchers conducted a retrospective review of the medical records of adults who underwent abdominal ultrasound and colonoscopy at a single hospital in China from January 2018 to December 2022 to determine NAFLD status and presence of polyps.
• Multivariate logistic regression analysis was used to detect associations between NAFLD and adenomatous and nonadenomatous polyps.

TAKEAWAY:

• Overall, 36.6% of the 3,028 patients had adenomatous polyps, 10.7% had nonadenomatous polyps, and 52.7% were polyp free.
• The higher frequency of NAFLD was significant in adults with adenomatous polyps (66.9%) but not in patients with nonadenomatous polyps (57%) vs. adults with no polyps (52.3%).
• In the fully adjusted model, NAFLD was a significant independent risk factor for adenomatous polyps (odds ratio [OR], 1.6; P < .0001) but not for nonadenomatous polyps (OR, 1.0; P = .813).
• The association between NAFLD and adenomatous polyps was statistically significant in both men (OR, 1.8) and women (OR, 1.4).

IN PRACTICE:

“Our results clearly demonstrated that NAFLD is associated with the development of colorectal adenomatous polyps in males and females, but is not associated with an increased risk of nonadenomatous polyps. The findings provide new insight into the prevention of colorectal cancer in NAFLD patients,” the authors wrote.

SOURCE:

The study was co-led by Yingxue Yang and Yajie Teng, The First People’s Hospital of Kunshan, Suzhou, China. It was published online in the European Journal of Gastroenterology & Hepatology. The study had no specific funding.

LIMITATIONS:

The diagnosis of NAFLD was by ultrasound rather than by liver biopsy. The study’s cross-sectional design precludes conclusions about causality between NAFLD and the risk for colorectal adenomatous polyps. The study involved a single center.

DISCLOSURES:

The authors have disclosed no conflicts of interest.
 

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

TOPLINE:

Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for precancerous colorectal adenomatous polyps in men and women, according to results of a large study.

METHODOLOGY:

• Researchers conducted a retrospective review of the medical records of adults who underwent abdominal ultrasound and colonoscopy at a single hospital in China from January 2018 to December 2022 to determine NAFLD status and presence of polyps.
• Multivariate logistic regression analysis was used to detect associations between NAFLD and adenomatous and nonadenomatous polyps.

TAKEAWAY:

• Overall, 36.6% of the 3,028 patients had adenomatous polyps, 10.7% had nonadenomatous polyps, and 52.7% were polyp free.
• The higher frequency of NAFLD was significant in adults with adenomatous polyps (66.9%) but not in patients with nonadenomatous polyps (57%) vs. adults with no polyps (52.3%).
• In the fully adjusted model, NAFLD was a significant independent risk factor for adenomatous polyps (odds ratio [OR], 1.6; P < .0001) but not for nonadenomatous polyps (OR, 1.0; P = .813).
• The association between NAFLD and adenomatous polyps was statistically significant in both men (OR, 1.8) and women (OR, 1.4).

IN PRACTICE:

“Our results clearly demonstrated that NAFLD is associated with the development of colorectal adenomatous polyps in males and females, but is not associated with an increased risk of nonadenomatous polyps. The findings provide new insight into the prevention of colorectal cancer in NAFLD patients,” the authors wrote.

SOURCE:

The study was co-led by Yingxue Yang and Yajie Teng, The First People’s Hospital of Kunshan, Suzhou, China. It was published online in the European Journal of Gastroenterology & Hepatology. The study had no specific funding.

LIMITATIONS:

The diagnosis of NAFLD was by ultrasound rather than by liver biopsy. The study’s cross-sectional design precludes conclusions about causality between NAFLD and the risk for colorectal adenomatous polyps. The study involved a single center.

DISCLOSURES:

The authors have disclosed no conflicts of interest.
 

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

TOPLINE:

Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for precancerous colorectal adenomatous polyps in men and women, according to results of a large study.

METHODOLOGY:

• Researchers conducted a retrospective review of the medical records of adults who underwent abdominal ultrasound and colonoscopy at a single hospital in China from January 2018 to December 2022 to determine NAFLD status and presence of polyps.
• Multivariate logistic regression analysis was used to detect associations between NAFLD and adenomatous and nonadenomatous polyps.

TAKEAWAY:

• Overall, 36.6% of the 3,028 patients had adenomatous polyps, 10.7% had nonadenomatous polyps, and 52.7% were polyp free.
• The higher frequency of NAFLD was significant in adults with adenomatous polyps (66.9%) but not in patients with nonadenomatous polyps (57%) vs. adults with no polyps (52.3%).
• In the fully adjusted model, NAFLD was a significant independent risk factor for adenomatous polyps (odds ratio [OR], 1.6; P < .0001) but not for nonadenomatous polyps (OR, 1.0; P = .813).
• The association between NAFLD and adenomatous polyps was statistically significant in both men (OR, 1.8) and women (OR, 1.4).

IN PRACTICE:

“Our results clearly demonstrated that NAFLD is associated with the development of colorectal adenomatous polyps in males and females, but is not associated with an increased risk of nonadenomatous polyps. The findings provide new insight into the prevention of colorectal cancer in NAFLD patients,” the authors wrote.

SOURCE:

The study was co-led by Yingxue Yang and Yajie Teng, The First People’s Hospital of Kunshan, Suzhou, China. It was published online in the European Journal of Gastroenterology & Hepatology. The study had no specific funding.

LIMITATIONS:

The diagnosis of NAFLD was by ultrasound rather than by liver biopsy. The study’s cross-sectional design precludes conclusions about causality between NAFLD and the risk for colorectal adenomatous polyps. The study involved a single center.

DISCLOSURES:

The authors have disclosed no conflicts of interest.
 

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

AMSTERDAM – For patients hospitalized for acute heart failure, initiating treatment with the SGLT2 inhibitor dapagliflozin (Farxiga, AstraZeneca) before hospital discharge was safe, it appeared to improve diuresis and natriuresis while reducing the administered diuretic dose, and it meant quicker initiation of guideline-directed therapy in a controlled study of 238 patients.

Treatment with dapagliflozin was begun for people with heart failure on their first day of hospitalization for an acute episode. Such treatment “can be safely started to optimize a key medication,” Zachary Cox, PharmD, said at the annual congress of the European Society of Cardiology. It improved fluid removal, as evidenced in the “totality of diuretic measures,” it resulted in reduced doses of IV diuretics, and it shortened length of stay in the hospital.

In current U.S. practice, about 80% of people hospitalized with heart failure do not initially receive treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor during their hospital stay when they are not already taking an agent from the class, noted Dr. Cox, professor of pharmacy at Lipscomb University College of Pharmacy in Nashville, Tenn.

Physicians are often uncomfortable changing a patient’s medications on the first day of a hospitalization, he noted. “Our results should embolden physicians” to begin treatment with an SGLT2 inhibitor early during hospitalization and to then continue it chronically, Dr. Cox said in a press briefing.

“Despite the messaging [from guidelines], we still see hesitancy. We hope more evidence of safety will improve uptake.” The study’s “key message is to start guideline-directed medical therapy early,” prior to hospital discharge, Dr. Cox concluded.
 

“Some support” for SGLT2 inhibitors

The study results “provide some support for SGLT2 inhibitors facilitating decongestion and hospital discharge without observed safety issues,” said Stephen D. Wiviott, MD, designated discussant for the report and a cardiologist and professor at Harvard Medical School in Boston.

While initiation of an SGLT2 inhibitor during an acute heart failure hospitalization received endorsement as a top management priority in both the 2023 heart failure guidelines of the European Society of Cardiology and in 2022 U.S. guidelines, evidence of the safety and efficacy of this approach has been scanty, Dr. Wiviott noted.

Two prior studies addressed the issue. The SOLOIST-WHF trial tested the combined SGLT1 and SGLT2 inhibitor sotagliflozin (Inpefa, Lexicon) for patients recently hospitalized for heart failure, but only 142 of the 596 participants who were randomly assigned to receive sotagliflozin began receiving it at least a day before hospital discharge; for the remaining 454, treatment with sotagliflozin began on their discharge day, noted Dr. Wiviott.

In the EMPULSE trial, 530 people hospitalized for acute heart failure were randomly assigned to initially receive empagliflozin (Jardiance, Boehringer Ingelheim and Lilly) or placebo during hospitalization. The primary endpoint was largely driven by an improvement in the patient-reported outcome, as assessed on the basis of the Kansas City Cardiomyopathy Questionnaire Total Symptom Score, Dr. Wiviott added.

The DICTATE-AHF study included 238 adults who were within 24 hours of first presenting to any of six participating U.S. hospitals with hypervolemic acute heart failure. All patients underwent a standard treatment protocol with IV loop diuretics, and half received additional, open-label treatment with a daily 10-mg dose of dapagliflozin.

The average age of the patients was 65 years, 71% had type 2 diabetes (the study excluded people with type 1 diabetes), and about half had a left ventricular ejection fraction of 40% or less.
 

Similar weight loss with lower diuretics dose

The study’s primary outcome was a measure of diuretic efficiency, calculated as a person’s cumulative weight change divided by the cumulative dose of loop diuretics.

Both treatment arms experienced nearly identical weight loss, but for the people who received dapagliflozin, this occurred with a lower cumulative dose of diuretics. The diuretic efficiency with dapagliflozin produced comparable weight loss with a 35% lower amount of loop diuretic dose, a difference that fell just short of significance (P = .06).

However, treatment with dapagliflozin also significantly boosted 24-hour natriuresis and 24-hour diuresis, and it significantly shortened the time to stopping treatment with IV diuretics and to hospital discharge, Dr. Cox reported. Dapagliflozin initiation and ongoing treatment was also safe and well tolerated compared with usual care.

The fact that the primary endpoint fell short of significance was “largely related” to the study’s relatively small size, Dr. Wiviott suggested. He noted that the DAPA ACT HF-TIMI 68 study, which is a much larger and potentially more definitive study of the safety and efficacy of dapagliflozin in comparison with usual care for patients with acute heart failure, is in progress. The study includes about 2,400 patients.

The primary outcome is the combined rate of cardiovascular death or worsening heart failure during the 2 months following randomization. Results are expected in 2024.

DICTATE-AHF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Cox has received research funding from AstraZeneca and has been a consultant to Roche and Translational Catalyst. Dr. Wiviott has received research funding from AstraZeneca and from Merck and has been a consultant to Icon Clinical and Novo Nordisk.
 

A version of this article appeared on Medscape.com.

AMSTERDAM – For patients hospitalized for acute heart failure, initiating treatment with the SGLT2 inhibitor dapagliflozin (Farxiga, AstraZeneca) before hospital discharge was safe, it appeared to improve diuresis and natriuresis while reducing the administered diuretic dose, and it meant quicker initiation of guideline-directed therapy in a controlled study of 238 patients.

Treatment with dapagliflozin was begun for people with heart failure on their first day of hospitalization for an acute episode. Such treatment “can be safely started to optimize a key medication,” Zachary Cox, PharmD, said at the annual congress of the European Society of Cardiology. It improved fluid removal, as evidenced in the “totality of diuretic measures,” it resulted in reduced doses of IV diuretics, and it shortened length of stay in the hospital.

In current U.S. practice, about 80% of people hospitalized with heart failure do not initially receive treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor during their hospital stay when they are not already taking an agent from the class, noted Dr. Cox, professor of pharmacy at Lipscomb University College of Pharmacy in Nashville, Tenn.

Physicians are often uncomfortable changing a patient’s medications on the first day of a hospitalization, he noted. “Our results should embolden physicians” to begin treatment with an SGLT2 inhibitor early during hospitalization and to then continue it chronically, Dr. Cox said in a press briefing.

“Despite the messaging [from guidelines], we still see hesitancy. We hope more evidence of safety will improve uptake.” The study’s “key message is to start guideline-directed medical therapy early,” prior to hospital discharge, Dr. Cox concluded.
 

“Some support” for SGLT2 inhibitors

The study results “provide some support for SGLT2 inhibitors facilitating decongestion and hospital discharge without observed safety issues,” said Stephen D. Wiviott, MD, designated discussant for the report and a cardiologist and professor at Harvard Medical School in Boston.

While initiation of an SGLT2 inhibitor during an acute heart failure hospitalization received endorsement as a top management priority in both the 2023 heart failure guidelines of the European Society of Cardiology and in 2022 U.S. guidelines, evidence of the safety and efficacy of this approach has been scanty, Dr. Wiviott noted.

Two prior studies addressed the issue. The SOLOIST-WHF trial tested the combined SGLT1 and SGLT2 inhibitor sotagliflozin (Inpefa, Lexicon) for patients recently hospitalized for heart failure, but only 142 of the 596 participants who were randomly assigned to receive sotagliflozin began receiving it at least a day before hospital discharge; for the remaining 454, treatment with sotagliflozin began on their discharge day, noted Dr. Wiviott.

In the EMPULSE trial, 530 people hospitalized for acute heart failure were randomly assigned to initially receive empagliflozin (Jardiance, Boehringer Ingelheim and Lilly) or placebo during hospitalization. The primary endpoint was largely driven by an improvement in the patient-reported outcome, as assessed on the basis of the Kansas City Cardiomyopathy Questionnaire Total Symptom Score, Dr. Wiviott added.

The DICTATE-AHF study included 238 adults who were within 24 hours of first presenting to any of six participating U.S. hospitals with hypervolemic acute heart failure. All patients underwent a standard treatment protocol with IV loop diuretics, and half received additional, open-label treatment with a daily 10-mg dose of dapagliflozin.

The average age of the patients was 65 years, 71% had type 2 diabetes (the study excluded people with type 1 diabetes), and about half had a left ventricular ejection fraction of 40% or less.
 

Similar weight loss with lower diuretics dose

The study’s primary outcome was a measure of diuretic efficiency, calculated as a person’s cumulative weight change divided by the cumulative dose of loop diuretics.

Both treatment arms experienced nearly identical weight loss, but for the people who received dapagliflozin, this occurred with a lower cumulative dose of diuretics. The diuretic efficiency with dapagliflozin produced comparable weight loss with a 35% lower amount of loop diuretic dose, a difference that fell just short of significance (P = .06).

However, treatment with dapagliflozin also significantly boosted 24-hour natriuresis and 24-hour diuresis, and it significantly shortened the time to stopping treatment with IV diuretics and to hospital discharge, Dr. Cox reported. Dapagliflozin initiation and ongoing treatment was also safe and well tolerated compared with usual care.

The fact that the primary endpoint fell short of significance was “largely related” to the study’s relatively small size, Dr. Wiviott suggested. He noted that the DAPA ACT HF-TIMI 68 study, which is a much larger and potentially more definitive study of the safety and efficacy of dapagliflozin in comparison with usual care for patients with acute heart failure, is in progress. The study includes about 2,400 patients.

The primary outcome is the combined rate of cardiovascular death or worsening heart failure during the 2 months following randomization. Results are expected in 2024.

DICTATE-AHF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Cox has received research funding from AstraZeneca and has been a consultant to Roche and Translational Catalyst. Dr. Wiviott has received research funding from AstraZeneca and from Merck and has been a consultant to Icon Clinical and Novo Nordisk.
 

A version of this article appeared on Medscape.com.

AMSTERDAM – For patients hospitalized for acute heart failure, initiating treatment with the SGLT2 inhibitor dapagliflozin (Farxiga, AstraZeneca) before hospital discharge was safe, it appeared to improve diuresis and natriuresis while reducing the administered diuretic dose, and it meant quicker initiation of guideline-directed therapy in a controlled study of 238 patients.

Treatment with dapagliflozin was begun for people with heart failure on their first day of hospitalization for an acute episode. Such treatment “can be safely started to optimize a key medication,” Zachary Cox, PharmD, said at the annual congress of the European Society of Cardiology. It improved fluid removal, as evidenced in the “totality of diuretic measures,” it resulted in reduced doses of IV diuretics, and it shortened length of stay in the hospital.

In current U.S. practice, about 80% of people hospitalized with heart failure do not initially receive treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor during their hospital stay when they are not already taking an agent from the class, noted Dr. Cox, professor of pharmacy at Lipscomb University College of Pharmacy in Nashville, Tenn.

Physicians are often uncomfortable changing a patient’s medications on the first day of a hospitalization, he noted. “Our results should embolden physicians” to begin treatment with an SGLT2 inhibitor early during hospitalization and to then continue it chronically, Dr. Cox said in a press briefing.

“Despite the messaging [from guidelines], we still see hesitancy. We hope more evidence of safety will improve uptake.” The study’s “key message is to start guideline-directed medical therapy early,” prior to hospital discharge, Dr. Cox concluded.
 

“Some support” for SGLT2 inhibitors

The study results “provide some support for SGLT2 inhibitors facilitating decongestion and hospital discharge without observed safety issues,” said Stephen D. Wiviott, MD, designated discussant for the report and a cardiologist and professor at Harvard Medical School in Boston.

While initiation of an SGLT2 inhibitor during an acute heart failure hospitalization received endorsement as a top management priority in both the 2023 heart failure guidelines of the European Society of Cardiology and in 2022 U.S. guidelines, evidence of the safety and efficacy of this approach has been scanty, Dr. Wiviott noted.

Two prior studies addressed the issue. The SOLOIST-WHF trial tested the combined SGLT1 and SGLT2 inhibitor sotagliflozin (Inpefa, Lexicon) for patients recently hospitalized for heart failure, but only 142 of the 596 participants who were randomly assigned to receive sotagliflozin began receiving it at least a day before hospital discharge; for the remaining 454, treatment with sotagliflozin began on their discharge day, noted Dr. Wiviott.

In the EMPULSE trial, 530 people hospitalized for acute heart failure were randomly assigned to initially receive empagliflozin (Jardiance, Boehringer Ingelheim and Lilly) or placebo during hospitalization. The primary endpoint was largely driven by an improvement in the patient-reported outcome, as assessed on the basis of the Kansas City Cardiomyopathy Questionnaire Total Symptom Score, Dr. Wiviott added.

The DICTATE-AHF study included 238 adults who were within 24 hours of first presenting to any of six participating U.S. hospitals with hypervolemic acute heart failure. All patients underwent a standard treatment protocol with IV loop diuretics, and half received additional, open-label treatment with a daily 10-mg dose of dapagliflozin.

The average age of the patients was 65 years, 71% had type 2 diabetes (the study excluded people with type 1 diabetes), and about half had a left ventricular ejection fraction of 40% or less.
 

Similar weight loss with lower diuretics dose

The study’s primary outcome was a measure of diuretic efficiency, calculated as a person’s cumulative weight change divided by the cumulative dose of loop diuretics.

Both treatment arms experienced nearly identical weight loss, but for the people who received dapagliflozin, this occurred with a lower cumulative dose of diuretics. The diuretic efficiency with dapagliflozin produced comparable weight loss with a 35% lower amount of loop diuretic dose, a difference that fell just short of significance (P = .06).

However, treatment with dapagliflozin also significantly boosted 24-hour natriuresis and 24-hour diuresis, and it significantly shortened the time to stopping treatment with IV diuretics and to hospital discharge, Dr. Cox reported. Dapagliflozin initiation and ongoing treatment was also safe and well tolerated compared with usual care.

The fact that the primary endpoint fell short of significance was “largely related” to the study’s relatively small size, Dr. Wiviott suggested. He noted that the DAPA ACT HF-TIMI 68 study, which is a much larger and potentially more definitive study of the safety and efficacy of dapagliflozin in comparison with usual care for patients with acute heart failure, is in progress. The study includes about 2,400 patients.

The primary outcome is the combined rate of cardiovascular death or worsening heart failure during the 2 months following randomization. Results are expected in 2024.

DICTATE-AHF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Cox has received research funding from AstraZeneca and has been a consultant to Roche and Translational Catalyst. Dr. Wiviott has received research funding from AstraZeneca and from Merck and has been a consultant to Icon Clinical and Novo Nordisk.
 

A version of this article appeared on Medscape.com.

With the advent of artificial intelligence (AI), the era of double reading of mammograms is likely coming to a close, according to Liane Philpotts, MD, a radiology and biomedical imaging professor at Yale University in New Haven, Conn.

The reason is because AI is proving to be as good as humans in interpreting mammograms, at least in the research setting.

In one of the latest reports, published online in Radiology, British investigators found that the performance of a commercially available AI system (INSIGHT MMG version 1.1.7.1 – Lunit) was essentially equivalent to over 500 specialized readers. The results are in line with other recent AI studies.

Double reading – having mammograms read by two clinicians to increase cancer detection rates – is common in the United Kingdom and elsewhere in Europe.

The British team compared the performance of 552 readers with Lunit’s AI program on the Personal Performance in Mammographic Screening exam, a quality assurance test which mammogram readers in the United Kingdom are required to take twice a year. Readers assign a malignancy score to 60 challenging cases, a mix of normal breasts and breasts with benign and cancerous lesions. The study included two test sessions for a total of 120 breast screenings.

Fifty-seven percent of the readers in the study were board-certified radiologists, 37% were radiographers, and 6% were breast clinicians. Each read at least 5,000 mammograms a year.

There was no difference in overall performance between the AI program and the human readers (AUC 0.93 vs. 0.88, P = .15).

Commenting in an editorial published with the investigation, Dr. Philpotts said the results “suggest that AI could confidently act as a second reader to decrease workloads.”

As for the United States, where double reading is generally not done, she pointed out that “many U.S. radiologists interpreting mammograms are nonspecialized and do not read high volumes of mammograms. Thus, the AI system evaluated in the study “could be used as a supplemental tool to aid the performance of readers in the United States or in other countries where screening programs use a single reading.”

There was also no difference in sensitivity between AI and human readers (84% vs. 90%, P = .34), but the AI algorithm had a higher specificity (89% vs. 76%, P = .003).

Using AI recall scores that matched the average human reader performance (90% sensitivity, 76% specificity), there was no difference with AI in regard to sensitivity (91%, P = .73) or specificity (77%, P = .85), but the investigators noted the power of the analysis was limited.

Overall, “diagnostic performance of AI was comparable with that of the average human reader.” It seems “increasingly likely that AI will eventually play a part in the interpretation of screening mammograms,” said investigators led by Yan Chen, PhD, of the Nottingham Breast Institute in England.

“That the AI system was able to match the performance of the average reader in this specialized group of mammogram readers indicates the robustness of this AI algorithm,” Dr. Philpotts said.

However, there are some caveats.

For one, the system was designed for 2D mammography, the current standard of care in the United Kingdom, while digital breast tomosynthesis (DBT) is replacing 2D mammography in the United States.

In the United States, “AI algorithms specific to DBT are necessary and will need to be reliable and reproducible to be embraced by radiologists,” Dr. Philpotts said.

Also in the United Kingdom, screening is performed at 3-year intervals in women aged 50-70 years old, which means that the study population was enriched for older women with less-dense breasts. Screening generally starts earlier in the United States and includes premenopausal women with denser breasts.

A recent study from Korea, where many women have dense breasts, found that 2D mammography and supplementary ultrasound outperformed AI for cancer detection.

“This underscores the challenges of finding cancers in dense breasts, which plague both radiologists and AI alike, and provides evidence that breast density is an important factor to consider when evaluating AI performance,” Dr. Philpotts said.

The work was funded by Lunit, the maker of the AI program used in the study. The investigators and Dr. Philpotts had no disclosures.

With the advent of artificial intelligence (AI), the era of double reading of mammograms is likely coming to a close, according to Liane Philpotts, MD, a radiology and biomedical imaging professor at Yale University in New Haven, Conn.

The reason is because AI is proving to be as good as humans in interpreting mammograms, at least in the research setting.

In one of the latest reports, published online in Radiology, British investigators found that the performance of a commercially available AI system (INSIGHT MMG version 1.1.7.1 – Lunit) was essentially equivalent to over 500 specialized readers. The results are in line with other recent AI studies.

Double reading – having mammograms read by two clinicians to increase cancer detection rates – is common in the United Kingdom and elsewhere in Europe.

The British team compared the performance of 552 readers with Lunit’s AI program on the Personal Performance in Mammographic Screening exam, a quality assurance test which mammogram readers in the United Kingdom are required to take twice a year. Readers assign a malignancy score to 60 challenging cases, a mix of normal breasts and breasts with benign and cancerous lesions. The study included two test sessions for a total of 120 breast screenings.

Fifty-seven percent of the readers in the study were board-certified radiologists, 37% were radiographers, and 6% were breast clinicians. Each read at least 5,000 mammograms a year.

There was no difference in overall performance between the AI program and the human readers (AUC 0.93 vs. 0.88, P = .15).

Commenting in an editorial published with the investigation, Dr. Philpotts said the results “suggest that AI could confidently act as a second reader to decrease workloads.”

As for the United States, where double reading is generally not done, she pointed out that “many U.S. radiologists interpreting mammograms are nonspecialized and do not read high volumes of mammograms. Thus, the AI system evaluated in the study “could be used as a supplemental tool to aid the performance of readers in the United States or in other countries where screening programs use a single reading.”

There was also no difference in sensitivity between AI and human readers (84% vs. 90%, P = .34), but the AI algorithm had a higher specificity (89% vs. 76%, P = .003).

Using AI recall scores that matched the average human reader performance (90% sensitivity, 76% specificity), there was no difference with AI in regard to sensitivity (91%, P = .73) or specificity (77%, P = .85), but the investigators noted the power of the analysis was limited.

Overall, “diagnostic performance of AI was comparable with that of the average human reader.” It seems “increasingly likely that AI will eventually play a part in the interpretation of screening mammograms,” said investigators led by Yan Chen, PhD, of the Nottingham Breast Institute in England.

“That the AI system was able to match the performance of the average reader in this specialized group of mammogram readers indicates the robustness of this AI algorithm,” Dr. Philpotts said.

However, there are some caveats.

For one, the system was designed for 2D mammography, the current standard of care in the United Kingdom, while digital breast tomosynthesis (DBT) is replacing 2D mammography in the United States.

In the United States, “AI algorithms specific to DBT are necessary and will need to be reliable and reproducible to be embraced by radiologists,” Dr. Philpotts said.

Also in the United Kingdom, screening is performed at 3-year intervals in women aged 50-70 years old, which means that the study population was enriched for older women with less-dense breasts. Screening generally starts earlier in the United States and includes premenopausal women with denser breasts.

A recent study from Korea, where many women have dense breasts, found that 2D mammography and supplementary ultrasound outperformed AI for cancer detection.

“This underscores the challenges of finding cancers in dense breasts, which plague both radiologists and AI alike, and provides evidence that breast density is an important factor to consider when evaluating AI performance,” Dr. Philpotts said.

The work was funded by Lunit, the maker of the AI program used in the study. The investigators and Dr. Philpotts had no disclosures.

With the advent of artificial intelligence (AI), the era of double reading of mammograms is likely coming to a close, according to Liane Philpotts, MD, a radiology and biomedical imaging professor at Yale University in New Haven, Conn.

The reason is because AI is proving to be as good as humans in interpreting mammograms, at least in the research setting.

In one of the latest reports, published online in Radiology, British investigators found that the performance of a commercially available AI system (INSIGHT MMG version 1.1.7.1 – Lunit) was essentially equivalent to over 500 specialized readers. The results are in line with other recent AI studies.

Double reading – having mammograms read by two clinicians to increase cancer detection rates – is common in the United Kingdom and elsewhere in Europe.

The British team compared the performance of 552 readers with Lunit’s AI program on the Personal Performance in Mammographic Screening exam, a quality assurance test which mammogram readers in the United Kingdom are required to take twice a year. Readers assign a malignancy score to 60 challenging cases, a mix of normal breasts and breasts with benign and cancerous lesions. The study included two test sessions for a total of 120 breast screenings.

Fifty-seven percent of the readers in the study were board-certified radiologists, 37% were radiographers, and 6% were breast clinicians. Each read at least 5,000 mammograms a year.

There was no difference in overall performance between the AI program and the human readers (AUC 0.93 vs. 0.88, P = .15).

Commenting in an editorial published with the investigation, Dr. Philpotts said the results “suggest that AI could confidently act as a second reader to decrease workloads.”

As for the United States, where double reading is generally not done, she pointed out that “many U.S. radiologists interpreting mammograms are nonspecialized and do not read high volumes of mammograms. Thus, the AI system evaluated in the study “could be used as a supplemental tool to aid the performance of readers in the United States or in other countries where screening programs use a single reading.”

There was also no difference in sensitivity between AI and human readers (84% vs. 90%, P = .34), but the AI algorithm had a higher specificity (89% vs. 76%, P = .003).

Using AI recall scores that matched the average human reader performance (90% sensitivity, 76% specificity), there was no difference with AI in regard to sensitivity (91%, P = .73) or specificity (77%, P = .85), but the investigators noted the power of the analysis was limited.

Overall, “diagnostic performance of AI was comparable with that of the average human reader.” It seems “increasingly likely that AI will eventually play a part in the interpretation of screening mammograms,” said investigators led by Yan Chen, PhD, of the Nottingham Breast Institute in England.

“That the AI system was able to match the performance of the average reader in this specialized group of mammogram readers indicates the robustness of this AI algorithm,” Dr. Philpotts said.

However, there are some caveats.

For one, the system was designed for 2D mammography, the current standard of care in the United Kingdom, while digital breast tomosynthesis (DBT) is replacing 2D mammography in the United States.

In the United States, “AI algorithms specific to DBT are necessary and will need to be reliable and reproducible to be embraced by radiologists,” Dr. Philpotts said.

Also in the United Kingdom, screening is performed at 3-year intervals in women aged 50-70 years old, which means that the study population was enriched for older women with less-dense breasts. Screening generally starts earlier in the United States and includes premenopausal women with denser breasts.

A recent study from Korea, where many women have dense breasts, found that 2D mammography and supplementary ultrasound outperformed AI for cancer detection.

“This underscores the challenges of finding cancers in dense breasts, which plague both radiologists and AI alike, and provides evidence that breast density is an important factor to consider when evaluating AI performance,” Dr. Philpotts said.

The work was funded by Lunit, the maker of the AI program used in the study. The investigators and Dr. Philpotts had no disclosures.

The Barbie movie is generating a lot of feelings, ranging from praise to vitriol. However one feels about the movie, let’s all pause and reflect for a moment on the fact that the number-one grossing film of 2023 is about our childhood doll trying to treat her anxiety disorder.

Eva Ritvo

“Life imitates art more than art imitates life.” So said Oscar Wilde in 1889.

When my adult daughter, a childhood Barbie enthusiast, asked me to see the film, we put on pink and went. Twice. Little did I know that it would stir up so many thoughts and feelings. The one I want to share is how blessed I feel at this moment in time to be a mental health care provider! No longer is mental health something to be whispered about at the water cooler; instead, even Barbie is suffering. And with all the controversy in the press about the movie, no one seems at all surprised by this storyline.

I was raised by two child psychiatrists and have been practicing as an adult psychiatrist since 1991. The start of the pandemic was the most difficult time of my career, as almost every patient was struggling simultaneously, as was I. Three long years later, we are gradually emerging from our shared trauma. How ironic, now with the opportunity to go back to work, I have elected to maintain the majority of my practice online from home. It seems that most patients and providers prefer this mode of treatment, with a full 90 percent of practitioners saying they are using a hybrid model.

As mental health professionals, we know that anywhere from 3% to 49% of those experiencing trauma will develop posttraumatic stress disorder (PTSD), and we have been trained to treat them.

But what happens when an entire global population is exposed simultaneously to trauma? Historians and social scientists refer to such events by many different names, such as: Singularity, Black Swan Event, and Tipping Point. These events are incredibly rare, and afterwards everything is different. These global traumas always lead to massive change.

I think we are at that tipping point. This is the singularity. This is our Black Swan Event. Within a 3-year span, we have experienced the following:

• A global traumatic event (COVID-19).
• A sudden and seemingly permanent shift from office to remote video meetings mostly from home.
• Upending of traditional fundamentals of the stock market as the game literally stopped in January 2021.
• Rapid and widespread availability of Artificial Intelligence.
• The first generation to be fully raised on the Internet and social media (Gen Z) is now entering the workforce.
• Ongoing war in Ukraine.

That’s already an overwhelming list, and I could go on, but let’s get back to Barbie’s anxiety disorder.

The awareness about and acceptance of mental health issues has never been higher. The access to treatment never greater. There are now more online therapy options than ever. Treatment options have dramatically expanded in recent years, from Transcranial Magnetic Stimulation (TMS) to ketamine centers and psychedelics, as well as more mainstream options such as dialectical behavior therapy (DBT), cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitors (SSRIs), and so many more.

What is particularly unique about this moment is the direct access to care. Self-help books abound with many making it to the New York Times bestseller list. YouTube is loaded with fantastic content on overcoming many mental health issues, although one should be careful with selecting reliable sources. Apps like HeadSpace and Calm are being downloaded by millions of people around the globe. Investors provided a record-breaking $1.5 billion to mental health startups in 2020 alone.

For most practitioners, our phones have been ringing off the hook since 2020. Applications to psychology, psychiatric residency, social work, and counseling degree programs are on the rise, with workforce shortages expected to continue for decades. Psychological expertise has been embraced by businesses especially for DEI (diversity, equity, and inclusion). Mental health experts are the most asked-for experts through media request services. Elite athletes are talking openly about bringing us on their teams.

In this unique moment, when everything seems set to transform into something else, it is time for mental health professionals to exert some agency and influence over where mental health will go from here. I think the next frontier for mental health specialists is to figure out how to speak collectively and help guide society.

Neil Howe, in his sweeping book “The Fourth Turning is Here,” says we have another 10 years in this “Millennial Crisis” phase. He calls this our “winter,” and it remains to be seen how we will emerge from our current challenges. I think we can make a difference.

If the Barbie movie is indeed a canary in the coal mine, I see positive trends ahead as we move past some of the societal and structural issues facing us, and work together to create a more open and egalitarian society. We must find creative solutions that will solve truly massive problems threatening our well-being and perhaps even our existence.

There has never been a better time to be (or become!) a mental health professional. I am so grateful to be able to continue to practice and share my thoughts with you here from my home office, and I hope you can take a break and see this movie, which is not only entertaining but also thought- and emotion-provoking.

Dr. Ritvo has almost 30 years’ experience in psychiatry and is currently practicing telemedicine. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018). She has no conflicts of interest.

The Barbie movie is generating a lot of feelings, ranging from praise to vitriol. However one feels about the movie, let’s all pause and reflect for a moment on the fact that the number-one grossing film of 2023 is about our childhood doll trying to treat her anxiety disorder.

Eva Ritvo

“Life imitates art more than art imitates life.” So said Oscar Wilde in 1889.

When my adult daughter, a childhood Barbie enthusiast, asked me to see the film, we put on pink and went. Twice. Little did I know that it would stir up so many thoughts and feelings. The one I want to share is how blessed I feel at this moment in time to be a mental health care provider! No longer is mental health something to be whispered about at the water cooler; instead, even Barbie is suffering. And with all the controversy in the press about the movie, no one seems at all surprised by this storyline.

I was raised by two child psychiatrists and have been practicing as an adult psychiatrist since 1991. The start of the pandemic was the most difficult time of my career, as almost every patient was struggling simultaneously, as was I. Three long years later, we are gradually emerging from our shared trauma. How ironic, now with the opportunity to go back to work, I have elected to maintain the majority of my practice online from home. It seems that most patients and providers prefer this mode of treatment, with a full 90 percent of practitioners saying they are using a hybrid model.

As mental health professionals, we know that anywhere from 3% to 49% of those experiencing trauma will develop posttraumatic stress disorder (PTSD), and we have been trained to treat them.

But what happens when an entire global population is exposed simultaneously to trauma? Historians and social scientists refer to such events by many different names, such as: Singularity, Black Swan Event, and Tipping Point. These events are incredibly rare, and afterwards everything is different. These global traumas always lead to massive change.

I think we are at that tipping point. This is the singularity. This is our Black Swan Event. Within a 3-year span, we have experienced the following:

• A global traumatic event (COVID-19).
• A sudden and seemingly permanent shift from office to remote video meetings mostly from home.
• Upending of traditional fundamentals of the stock market as the game literally stopped in January 2021.
• Rapid and widespread availability of Artificial Intelligence.
• The first generation to be fully raised on the Internet and social media (Gen Z) is now entering the workforce.
• Ongoing war in Ukraine.

That’s already an overwhelming list, and I could go on, but let’s get back to Barbie’s anxiety disorder.

The awareness about and acceptance of mental health issues has never been higher. The access to treatment never greater. There are now more online therapy options than ever. Treatment options have dramatically expanded in recent years, from Transcranial Magnetic Stimulation (TMS) to ketamine centers and psychedelics, as well as more mainstream options such as dialectical behavior therapy (DBT), cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitors (SSRIs), and so many more.

What is particularly unique about this moment is the direct access to care. Self-help books abound with many making it to the New York Times bestseller list. YouTube is loaded with fantastic content on overcoming many mental health issues, although one should be careful with selecting reliable sources. Apps like HeadSpace and Calm are being downloaded by millions of people around the globe. Investors provided a record-breaking $1.5 billion to mental health startups in 2020 alone.

For most practitioners, our phones have been ringing off the hook since 2020. Applications to psychology, psychiatric residency, social work, and counseling degree programs are on the rise, with workforce shortages expected to continue for decades. Psychological expertise has been embraced by businesses especially for DEI (diversity, equity, and inclusion). Mental health experts are the most asked-for experts through media request services. Elite athletes are talking openly about bringing us on their teams.

In this unique moment, when everything seems set to transform into something else, it is time for mental health professionals to exert some agency and influence over where mental health will go from here. I think the next frontier for mental health specialists is to figure out how to speak collectively and help guide society.

Neil Howe, in his sweeping book “The Fourth Turning is Here,” says we have another 10 years in this “Millennial Crisis” phase. He calls this our “winter,” and it remains to be seen how we will emerge from our current challenges. I think we can make a difference.

If the Barbie movie is indeed a canary in the coal mine, I see positive trends ahead as we move past some of the societal and structural issues facing us, and work together to create a more open and egalitarian society. We must find creative solutions that will solve truly massive problems threatening our well-being and perhaps even our existence.

There has never been a better time to be (or become!) a mental health professional. I am so grateful to be able to continue to practice and share my thoughts with you here from my home office, and I hope you can take a break and see this movie, which is not only entertaining but also thought- and emotion-provoking.

Dr. Ritvo has almost 30 years’ experience in psychiatry and is currently practicing telemedicine. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018). She has no conflicts of interest.

The Barbie movie is generating a lot of feelings, ranging from praise to vitriol. However one feels about the movie, let’s all pause and reflect for a moment on the fact that the number-one grossing film of 2023 is about our childhood doll trying to treat her anxiety disorder.

Eva Ritvo

“Life imitates art more than art imitates life.” So said Oscar Wilde in 1889.

When my adult daughter, a childhood Barbie enthusiast, asked me to see the film, we put on pink and went. Twice. Little did I know that it would stir up so many thoughts and feelings. The one I want to share is how blessed I feel at this moment in time to be a mental health care provider! No longer is mental health something to be whispered about at the water cooler; instead, even Barbie is suffering. And with all the controversy in the press about the movie, no one seems at all surprised by this storyline.

I was raised by two child psychiatrists and have been practicing as an adult psychiatrist since 1991. The start of the pandemic was the most difficult time of my career, as almost every patient was struggling simultaneously, as was I. Three long years later, we are gradually emerging from our shared trauma. How ironic, now with the opportunity to go back to work, I have elected to maintain the majority of my practice online from home. It seems that most patients and providers prefer this mode of treatment, with a full 90 percent of practitioners saying they are using a hybrid model.

As mental health professionals, we know that anywhere from 3% to 49% of those experiencing trauma will develop posttraumatic stress disorder (PTSD), and we have been trained to treat them.

But what happens when an entire global population is exposed simultaneously to trauma? Historians and social scientists refer to such events by many different names, such as: Singularity, Black Swan Event, and Tipping Point. These events are incredibly rare, and afterwards everything is different. These global traumas always lead to massive change.

I think we are at that tipping point. This is the singularity. This is our Black Swan Event. Within a 3-year span, we have experienced the following:

• A global traumatic event (COVID-19).
• A sudden and seemingly permanent shift from office to remote video meetings mostly from home.
• Upending of traditional fundamentals of the stock market as the game literally stopped in January 2021.
• Rapid and widespread availability of Artificial Intelligence.
• The first generation to be fully raised on the Internet and social media (Gen Z) is now entering the workforce.
• Ongoing war in Ukraine.

That’s already an overwhelming list, and I could go on, but let’s get back to Barbie’s anxiety disorder.

The awareness about and acceptance of mental health issues has never been higher. The access to treatment never greater. There are now more online therapy options than ever. Treatment options have dramatically expanded in recent years, from Transcranial Magnetic Stimulation (TMS) to ketamine centers and psychedelics, as well as more mainstream options such as dialectical behavior therapy (DBT), cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitors (SSRIs), and so many more.

What is particularly unique about this moment is the direct access to care. Self-help books abound with many making it to the New York Times bestseller list. YouTube is loaded with fantastic content on overcoming many mental health issues, although one should be careful with selecting reliable sources. Apps like HeadSpace and Calm are being downloaded by millions of people around the globe. Investors provided a record-breaking $1.5 billion to mental health startups in 2020 alone.

For most practitioners, our phones have been ringing off the hook since 2020. Applications to psychology, psychiatric residency, social work, and counseling degree programs are on the rise, with workforce shortages expected to continue for decades. Psychological expertise has been embraced by businesses especially for DEI (diversity, equity, and inclusion). Mental health experts are the most asked-for experts through media request services. Elite athletes are talking openly about bringing us on their teams.

In this unique moment, when everything seems set to transform into something else, it is time for mental health professionals to exert some agency and influence over where mental health will go from here. I think the next frontier for mental health specialists is to figure out how to speak collectively and help guide society.

Neil Howe, in his sweeping book “The Fourth Turning is Here,” says we have another 10 years in this “Millennial Crisis” phase. He calls this our “winter,” and it remains to be seen how we will emerge from our current challenges. I think we can make a difference.

If the Barbie movie is indeed a canary in the coal mine, I see positive trends ahead as we move past some of the societal and structural issues facing us, and work together to create a more open and egalitarian society. We must find creative solutions that will solve truly massive problems threatening our well-being and perhaps even our existence.

There has never been a better time to be (or become!) a mental health professional. I am so grateful to be able to continue to practice and share my thoughts with you here from my home office, and I hope you can take a break and see this movie, which is not only entertaining but also thought- and emotion-provoking.

Dr. Ritvo has almost 30 years’ experience in psychiatry and is currently practicing telemedicine. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018). She has no conflicts of interest.

Pulmonary Vascular & Cardiovascular Network

Cardiovascular Medicine and Surgery Section

Sepsis and septic shock still carry high morbidity and mortality in ICU patients despite recent improvements in care. Sepsis-induced cardiomyopathy (SICM), which complicates greater than 10% of sepsis and septic shock cases, carries a worse prognosis and is often underrecognized. Unfortunately, no universal definition of SICM exists, making diagnosis and evaluation of novel therapeutic options difficult. Initially described in the 1980s, common fundamental features of SICM include an acute and reversible decline in LVEF with typical resolution in days to weeks; RV, LV, or BiV dysfunction; LV dilation; diminished response to fluid resuscitation or catecholamines; and absence of acute coronary syndrome (L’Heureux, Sternberg et al, 2020). A definition of SICM based solely on LVEF is incomplete due to its reliance on cardiac loading conditions. Diagnostic advances using pulse contour analysis and echocardiographic measure of longitudinal strain hold promise in better characterizing cardiac dysfunction in sepsis (Beesley et al, 2018). SICM should further be distinguished from stress-induced cardiomyopathy or Takotsubo cardiomyopathy, which can also complicate cases of sepsis and is characterized by regional wall motion abnormalities, classically LV apical ballooning with preserved contractility of the basal segments. A movement toward a standard definition of SICM would allow a more rigorous evaluation of risk factors and future directions for therapy, including a potential role for mechanical circulatory support in patients who fail to improve with inotropic support.

CHEST

Looking for more information on sepsis? Visit CHEST’s Sepsis Topic Collection Page at chestnet.org/Topic-Collections/Sepsis for research, infographics, and more developed by the CHEST Sepsis Resources Steering Committee.

Tarun Kapoor, MD: Section Fellow-in-Training  
Andrew Petrilli, MD

Pulmonary Vascular & Cardiovascular Network

Cardiovascular Medicine and Surgery Section

Sepsis and septic shock still carry high morbidity and mortality in ICU patients despite recent improvements in care. Sepsis-induced cardiomyopathy (SICM), which complicates greater than 10% of sepsis and septic shock cases, carries a worse prognosis and is often underrecognized. Unfortunately, no universal definition of SICM exists, making diagnosis and evaluation of novel therapeutic options difficult. Initially described in the 1980s, common fundamental features of SICM include an acute and reversible decline in LVEF with typical resolution in days to weeks; RV, LV, or BiV dysfunction; LV dilation; diminished response to fluid resuscitation or catecholamines; and absence of acute coronary syndrome (L’Heureux, Sternberg et al, 2020). A definition of SICM based solely on LVEF is incomplete due to its reliance on cardiac loading conditions. Diagnostic advances using pulse contour analysis and echocardiographic measure of longitudinal strain hold promise in better characterizing cardiac dysfunction in sepsis (Beesley et al, 2018). SICM should further be distinguished from stress-induced cardiomyopathy or Takotsubo cardiomyopathy, which can also complicate cases of sepsis and is characterized by regional wall motion abnormalities, classically LV apical ballooning with preserved contractility of the basal segments. A movement toward a standard definition of SICM would allow a more rigorous evaluation of risk factors and future directions for therapy, including a potential role for mechanical circulatory support in patients who fail to improve with inotropic support.

CHEST

Looking for more information on sepsis? Visit CHEST’s Sepsis Topic Collection Page at chestnet.org/Topic-Collections/Sepsis for research, infographics, and more developed by the CHEST Sepsis Resources Steering Committee.

Tarun Kapoor, MD: Section Fellow-in-Training  
Andrew Petrilli, MD

Pulmonary Vascular & Cardiovascular Network

Cardiovascular Medicine and Surgery Section

Sepsis and septic shock still carry high morbidity and mortality in ICU patients despite recent improvements in care. Sepsis-induced cardiomyopathy (SICM), which complicates greater than 10% of sepsis and septic shock cases, carries a worse prognosis and is often underrecognized. Unfortunately, no universal definition of SICM exists, making diagnosis and evaluation of novel therapeutic options difficult. Initially described in the 1980s, common fundamental features of SICM include an acute and reversible decline in LVEF with typical resolution in days to weeks; RV, LV, or BiV dysfunction; LV dilation; diminished response to fluid resuscitation or catecholamines; and absence of acute coronary syndrome (L’Heureux, Sternberg et al, 2020). A definition of SICM based solely on LVEF is incomplete due to its reliance on cardiac loading conditions. Diagnostic advances using pulse contour analysis and echocardiographic measure of longitudinal strain hold promise in better characterizing cardiac dysfunction in sepsis (Beesley et al, 2018). SICM should further be distinguished from stress-induced cardiomyopathy or Takotsubo cardiomyopathy, which can also complicate cases of sepsis and is characterized by regional wall motion abnormalities, classically LV apical ballooning with preserved contractility of the basal segments. A movement toward a standard definition of SICM would allow a more rigorous evaluation of risk factors and future directions for therapy, including a potential role for mechanical circulatory support in patients who fail to improve with inotropic support.

CHEST

Looking for more information on sepsis? Visit CHEST’s Sepsis Topic Collection Page at chestnet.org/Topic-Collections/Sepsis for research, infographics, and more developed by the CHEST Sepsis Resources Steering Committee.

Tarun Kapoor, MD: Section Fellow-in-Training  
Andrew Petrilli, MD

It’s important to have counselors available for people diagnosed with clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenia of undetermined significance (CCUS), according to medical oncologist Lachelle D. Weeks, MD, PhD, a specialist in both conditions at the Dana Farber Cancer Institute, Boston.

The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.

CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.

CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.

A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.

With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.

Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.

Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.

The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.

“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.

High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.

The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.

“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.

“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.

The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.

It’s important to have counselors available for people diagnosed with clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenia of undetermined significance (CCUS), according to medical oncologist Lachelle D. Weeks, MD, PhD, a specialist in both conditions at the Dana Farber Cancer Institute, Boston.

The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.

CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.

CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.

A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.

With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.

Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.

Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.

The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.

“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.

High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.

The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.

“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.

“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.

The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.

It’s important to have counselors available for people diagnosed with clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenia of undetermined significance (CCUS), according to medical oncologist Lachelle D. Weeks, MD, PhD, a specialist in both conditions at the Dana Farber Cancer Institute, Boston.

The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.

CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.

CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.

A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.

With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.

Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.

Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.

The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.

“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.

High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.

The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.

“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.

“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.

The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.

The European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has recommended new measures designed to avoid topiramate (multiple brands) use during pregnancy.

While it’s well known that topiramate can cause major congenital malformations and fetal growth restriction when used during pregnancy, recent data also suggest a possibly increased risk for neurodevelopmental disorders when topiramate is used during pregnancy, the EMA said in a statement. 

The data include two observational studies that showed children born to mothers with epilepsy and who were exposed to topiramate in the womb may have a two- to threefold higher risk for neurodevelopmental disorders, in particular autism spectrum disorders (ASD), intellectual disability, or attention deficit hyperactivity disorder (ADHD), compared with children born to mothers with epilepsy not taking antiepileptic medication.

For patients using topiramate for the treatment of epilepsy, the PRAC now recommends that the medicine not be used during pregnancy unless no other suitable treatment is available.

The PRAC had also recommended a pregnancy prevention program to avoid exposure of the developing fetus to topiramate. “These measures will inform any woman or girl who is able to have children of the risks of taking topiramate during pregnancy and the need to avoid becoming pregnant while taking topiramate,” the EMA said.

Regardless of indication, the agency said topiramate should be used in women of childbearing age only when the following conditions of the pregnancy prevention program are met:

• A pregnancy test before starting treatment.
• Counseling about the risks of topiramate treatment and the need for highly effective contraception throughout treatment.
• A review of ongoing treatment at least annually by completion of a risk awareness form.

The PRAC recommends that health care professionals ensure women of childbearing age are fully aware of the risks of taking topiramate during pregnancy. The committee noted that alternative treatment options should be considered and the need for topiramate treatment should be reassessed at least annually.

The product information for topiramate-containing medicines will be updated to further highlight the risks for neurodevelopmental disorders and the additional safety measures to be taken.

Patients and health care professionals will be provided with educational materials regarding the risks of using topiramate during pregnancy, and a patient card will be provided to the patient with each medicine package. A visible warning will also be added to the outer packaging of the medicine.

The new PRAC recommendations will be sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position.
 

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

The European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has recommended new measures designed to avoid topiramate (multiple brands) use during pregnancy.

While it’s well known that topiramate can cause major congenital malformations and fetal growth restriction when used during pregnancy, recent data also suggest a possibly increased risk for neurodevelopmental disorders when topiramate is used during pregnancy, the EMA said in a statement. 

The data include two observational studies that showed children born to mothers with epilepsy and who were exposed to topiramate in the womb may have a two- to threefold higher risk for neurodevelopmental disorders, in particular autism spectrum disorders (ASD), intellectual disability, or attention deficit hyperactivity disorder (ADHD), compared with children born to mothers with epilepsy not taking antiepileptic medication.

For patients using topiramate for the treatment of epilepsy, the PRAC now recommends that the medicine not be used during pregnancy unless no other suitable treatment is available.

The PRAC had also recommended a pregnancy prevention program to avoid exposure of the developing fetus to topiramate. “These measures will inform any woman or girl who is able to have children of the risks of taking topiramate during pregnancy and the need to avoid becoming pregnant while taking topiramate,” the EMA said.

Regardless of indication, the agency said topiramate should be used in women of childbearing age only when the following conditions of the pregnancy prevention program are met:

• A pregnancy test before starting treatment.
• Counseling about the risks of topiramate treatment and the need for highly effective contraception throughout treatment.
• A review of ongoing treatment at least annually by completion of a risk awareness form.

The PRAC recommends that health care professionals ensure women of childbearing age are fully aware of the risks of taking topiramate during pregnancy. The committee noted that alternative treatment options should be considered and the need for topiramate treatment should be reassessed at least annually.

The product information for topiramate-containing medicines will be updated to further highlight the risks for neurodevelopmental disorders and the additional safety measures to be taken.

Patients and health care professionals will be provided with educational materials regarding the risks of using topiramate during pregnancy, and a patient card will be provided to the patient with each medicine package. A visible warning will also be added to the outer packaging of the medicine.

The new PRAC recommendations will be sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position.
 

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

The European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has recommended new measures designed to avoid topiramate (multiple brands) use during pregnancy.

While it’s well known that topiramate can cause major congenital malformations and fetal growth restriction when used during pregnancy, recent data also suggest a possibly increased risk for neurodevelopmental disorders when topiramate is used during pregnancy, the EMA said in a statement. 

The data include two observational studies that showed children born to mothers with epilepsy and who were exposed to topiramate in the womb may have a two- to threefold higher risk for neurodevelopmental disorders, in particular autism spectrum disorders (ASD), intellectual disability, or attention deficit hyperactivity disorder (ADHD), compared with children born to mothers with epilepsy not taking antiepileptic medication.

For patients using topiramate for the treatment of epilepsy, the PRAC now recommends that the medicine not be used during pregnancy unless no other suitable treatment is available.

The PRAC had also recommended a pregnancy prevention program to avoid exposure of the developing fetus to topiramate. “These measures will inform any woman or girl who is able to have children of the risks of taking topiramate during pregnancy and the need to avoid becoming pregnant while taking topiramate,” the EMA said.

Regardless of indication, the agency said topiramate should be used in women of childbearing age only when the following conditions of the pregnancy prevention program are met:

• A pregnancy test before starting treatment.
• Counseling about the risks of topiramate treatment and the need for highly effective contraception throughout treatment.
• A review of ongoing treatment at least annually by completion of a risk awareness form.

The PRAC recommends that health care professionals ensure women of childbearing age are fully aware of the risks of taking topiramate during pregnancy. The committee noted that alternative treatment options should be considered and the need for topiramate treatment should be reassessed at least annually.

The product information for topiramate-containing medicines will be updated to further highlight the risks for neurodevelopmental disorders and the additional safety measures to be taken.

Patients and health care professionals will be provided with educational materials regarding the risks of using topiramate during pregnancy, and a patient card will be provided to the patient with each medicine package. A visible warning will also be added to the outer packaging of the medicine.

The new PRAC recommendations will be sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position.
 

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

INTRODUCTION

Leptomeningeal metastasis (LM) is an extremely rare complication of gastroesophageal (GE) cancer. Diagnosis is challenging due to frequently nonspecific clinical presentations, limited sensitivity of diagnostic testing, and potential overlap with neurologic immune-related adverse events (irAE). We describe a case of metastatic gastroesophageal cancer on immunotherapy presenting with LM masquerading as polyneuropathy.

CASE REPORT

A 74-year-old male with HER2+ GE junction cancer with peritoneal metastases diagnosed 6 months ago, on maintenance trastuzumab/pembrolizumab and with no previous history of cranial or spinal disease, presented with worsening ataxia, headache, and diplopia for one month with multiple negative outpatient MRIs. Examination showed left abducens nerve palsy, dysmetria and absent deep tendon reflexes in upper and lower extremities. CT head was unremarkable, and MRI showed non-specific mild enhancement of the right optic nerve, symmetrical lumbosacral nerve roots and cauda equina concerning for paraneoplastic versus immunotherapy-related polyneuropathy. He was started on empiric high-dose corticosteroids. PET-CT was negative for FDG-avid lesions. Cerebrospinal fluid (CSF) analysis revealed moderate pleocytosis with many large atypical cells, elevated protein (118 mg/dL) and LDH (28 IU/L). Immunohistochemistry was positive for CDX2, CA 19-9, CK7, and pankeratin, consistent with metastatic adenocarcinoma, negative for HER2 in contrast to the original tumor. He subsequently developed hydrocephalus requiring a ventriculoperitoneal shunt. He received ten fractions of whole brain irradiation before electing to pursue hospice care.

DISCUSSION

LM is an extremely rare complication of GE cancer with an incidence of <0.2% and carries a poor prognosis. Differentiation between LM and irAE in patients on immunotherapy can be challenging. Diagnosis relies mostly on CSF cytology, and lumbar puncture should not be delayed in patients with new neurologic symptoms. Treatment options are intrathecal chemotherapy, radiation and steroids. A recent phase II trial has shown promise for intrathecal trastuzumab in patients with HER2+ cancers, but options for HER2 negative disease remain mostly palliative.

CONCLUSIONS

Our case highlights the need for suspecting this rare metastatic site, as early diagnosis and genetic characterization allow for exploring more treatment options including targeted therapies which may improve overall survival and quality of life.

INTRODUCTION

Leptomeningeal metastasis (LM) is an extremely rare complication of gastroesophageal (GE) cancer. Diagnosis is challenging due to frequently nonspecific clinical presentations, limited sensitivity of diagnostic testing, and potential overlap with neurologic immune-related adverse events (irAE). We describe a case of metastatic gastroesophageal cancer on immunotherapy presenting with LM masquerading as polyneuropathy.

CASE REPORT

A 74-year-old male with HER2+ GE junction cancer with peritoneal metastases diagnosed 6 months ago, on maintenance trastuzumab/pembrolizumab and with no previous history of cranial or spinal disease, presented with worsening ataxia, headache, and diplopia for one month with multiple negative outpatient MRIs. Examination showed left abducens nerve palsy, dysmetria and absent deep tendon reflexes in upper and lower extremities. CT head was unremarkable, and MRI showed non-specific mild enhancement of the right optic nerve, symmetrical lumbosacral nerve roots and cauda equina concerning for paraneoplastic versus immunotherapy-related polyneuropathy. He was started on empiric high-dose corticosteroids. PET-CT was negative for FDG-avid lesions. Cerebrospinal fluid (CSF) analysis revealed moderate pleocytosis with many large atypical cells, elevated protein (118 mg/dL) and LDH (28 IU/L). Immunohistochemistry was positive for CDX2, CA 19-9, CK7, and pankeratin, consistent with metastatic adenocarcinoma, negative for HER2 in contrast to the original tumor. He subsequently developed hydrocephalus requiring a ventriculoperitoneal shunt. He received ten fractions of whole brain irradiation before electing to pursue hospice care.

DISCUSSION

LM is an extremely rare complication of GE cancer with an incidence of <0.2% and carries a poor prognosis. Differentiation between LM and irAE in patients on immunotherapy can be challenging. Diagnosis relies mostly on CSF cytology, and lumbar puncture should not be delayed in patients with new neurologic symptoms. Treatment options are intrathecal chemotherapy, radiation and steroids. A recent phase II trial has shown promise for intrathecal trastuzumab in patients with HER2+ cancers, but options for HER2 negative disease remain mostly palliative.

CONCLUSIONS

Our case highlights the need for suspecting this rare metastatic site, as early diagnosis and genetic characterization allow for exploring more treatment options including targeted therapies which may improve overall survival and quality of life.

INTRODUCTION

Leptomeningeal metastasis (LM) is an extremely rare complication of gastroesophageal (GE) cancer. Diagnosis is challenging due to frequently nonspecific clinical presentations, limited sensitivity of diagnostic testing, and potential overlap with neurologic immune-related adverse events (irAE). We describe a case of metastatic gastroesophageal cancer on immunotherapy presenting with LM masquerading as polyneuropathy.

CASE REPORT

A 74-year-old male with HER2+ GE junction cancer with peritoneal metastases diagnosed 6 months ago, on maintenance trastuzumab/pembrolizumab and with no previous history of cranial or spinal disease, presented with worsening ataxia, headache, and diplopia for one month with multiple negative outpatient MRIs. Examination showed left abducens nerve palsy, dysmetria and absent deep tendon reflexes in upper and lower extremities. CT head was unremarkable, and MRI showed non-specific mild enhancement of the right optic nerve, symmetrical lumbosacral nerve roots and cauda equina concerning for paraneoplastic versus immunotherapy-related polyneuropathy. He was started on empiric high-dose corticosteroids. PET-CT was negative for FDG-avid lesions. Cerebrospinal fluid (CSF) analysis revealed moderate pleocytosis with many large atypical cells, elevated protein (118 mg/dL) and LDH (28 IU/L). Immunohistochemistry was positive for CDX2, CA 19-9, CK7, and pankeratin, consistent with metastatic adenocarcinoma, negative for HER2 in contrast to the original tumor. He subsequently developed hydrocephalus requiring a ventriculoperitoneal shunt. He received ten fractions of whole brain irradiation before electing to pursue hospice care.

DISCUSSION

LM is an extremely rare complication of GE cancer with an incidence of <0.2% and carries a poor prognosis. Differentiation between LM and irAE in patients on immunotherapy can be challenging. Diagnosis relies mostly on CSF cytology, and lumbar puncture should not be delayed in patients with new neurologic symptoms. Treatment options are intrathecal chemotherapy, radiation and steroids. A recent phase II trial has shown promise for intrathecal trastuzumab in patients with HER2+ cancers, but options for HER2 negative disease remain mostly palliative.

CONCLUSIONS

Our case highlights the need for suspecting this rare metastatic site, as early diagnosis and genetic characterization allow for exploring more treatment options including targeted therapies which may improve overall survival and quality of life.

PURPOSE

This quality improvement project aims to enhance the rate of germline genetic testing for prostate cancer at the Stratton VA Medical Center, improving risk reduction strategies and therapeutic options for patients.

BACKGROUND

Prostate cancer is prevalent at the Stratton VA Medical Center, yet the rate of genetic evaluation for prostate cancer remains suboptimal. National guidelines recommend genetic counseling and testing in specific patient populations. To address this gap, an interdisciplinary working group conducted gap analysis and root cause analysis, identifying four significant barriers.

METHODS 

The working group comprised medical oncologists, urologists, primary care physicians, genetics counselors, data experts, and a LEAN coach. Interventions included implementing a prostate cancer pathway to educate staff on genetic testing indications and integrating genetic testing screening into clinic visits. After the interventions were implemented in January 2022, patient charts were reviewed for all genetic referrals and new prostate cancer diagnoses from January to December 2022.

DATA ANALYSIS

Descriptive analysis was conducted on referral rates, evaluation visit completion rates, and genetic testing outcomes among prostate cancer patients.

RESULTS

During the study period, 59 prostate cancer patients were referred for genetic evaluation. Notably, this was a large increase from no genetic referrals for prostate cancer in the previous year. Among them, 43 completed the evaluation visit, and 34 underwent genetic testing. Noteworthy findings were observed in 5 patients, including 3 variants of unknown significance and 2 pathogenic germline variants: HOXB13 and BRCA2 mutations.

IMPLICATIONS

This project highlights the power of a collaborative, multidisciplinary approach to overcome barriers and enhance the quality of care for prostate cancer patients. The team’s use of gap analysis and root cause analysis successfully identified barriers and proposed solutions, leading to increased referrals and the identification of significant genetic findings. Continued efforts to improve access to germline genetic testing are crucial for enhanced patient care and improved outcomes.

PURPOSE

This quality improvement project aims to enhance the rate of germline genetic testing for prostate cancer at the Stratton VA Medical Center, improving risk reduction strategies and therapeutic options for patients.

BACKGROUND

Prostate cancer is prevalent at the Stratton VA Medical Center, yet the rate of genetic evaluation for prostate cancer remains suboptimal. National guidelines recommend genetic counseling and testing in specific patient populations. To address this gap, an interdisciplinary working group conducted gap analysis and root cause analysis, identifying four significant barriers.

METHODS 

The working group comprised medical oncologists, urologists, primary care physicians, genetics counselors, data experts, and a LEAN coach. Interventions included implementing a prostate cancer pathway to educate staff on genetic testing indications and integrating genetic testing screening into clinic visits. After the interventions were implemented in January 2022, patient charts were reviewed for all genetic referrals and new prostate cancer diagnoses from January to December 2022.

DATA ANALYSIS

Descriptive analysis was conducted on referral rates, evaluation visit completion rates, and genetic testing outcomes among prostate cancer patients.

RESULTS

During the study period, 59 prostate cancer patients were referred for genetic evaluation. Notably, this was a large increase from no genetic referrals for prostate cancer in the previous year. Among them, 43 completed the evaluation visit, and 34 underwent genetic testing. Noteworthy findings were observed in 5 patients, including 3 variants of unknown significance and 2 pathogenic germline variants: HOXB13 and BRCA2 mutations.

IMPLICATIONS

This project highlights the power of a collaborative, multidisciplinary approach to overcome barriers and enhance the quality of care for prostate cancer patients. The team’s use of gap analysis and root cause analysis successfully identified barriers and proposed solutions, leading to increased referrals and the identification of significant genetic findings. Continued efforts to improve access to germline genetic testing are crucial for enhanced patient care and improved outcomes.

PURPOSE

This quality improvement project aims to enhance the rate of germline genetic testing for prostate cancer at the Stratton VA Medical Center, improving risk reduction strategies and therapeutic options for patients.

BACKGROUND

Prostate cancer is prevalent at the Stratton VA Medical Center, yet the rate of genetic evaluation for prostate cancer remains suboptimal. National guidelines recommend genetic counseling and testing in specific patient populations. To address this gap, an interdisciplinary working group conducted gap analysis and root cause analysis, identifying four significant barriers.

METHODS 

The working group comprised medical oncologists, urologists, primary care physicians, genetics counselors, data experts, and a LEAN coach. Interventions included implementing a prostate cancer pathway to educate staff on genetic testing indications and integrating genetic testing screening into clinic visits. After the interventions were implemented in January 2022, patient charts were reviewed for all genetic referrals and new prostate cancer diagnoses from January to December 2022.

DATA ANALYSIS

Descriptive analysis was conducted on referral rates, evaluation visit completion rates, and genetic testing outcomes among prostate cancer patients.

RESULTS

During the study period, 59 prostate cancer patients were referred for genetic evaluation. Notably, this was a large increase from no genetic referrals for prostate cancer in the previous year. Among them, 43 completed the evaluation visit, and 34 underwent genetic testing. Noteworthy findings were observed in 5 patients, including 3 variants of unknown significance and 2 pathogenic germline variants: HOXB13 and BRCA2 mutations.

IMPLICATIONS

This project highlights the power of a collaborative, multidisciplinary approach to overcome barriers and enhance the quality of care for prostate cancer patients. The team’s use of gap analysis and root cause analysis successfully identified barriers and proposed solutions, leading to increased referrals and the identification of significant genetic findings. Continued efforts to improve access to germline genetic testing are crucial for enhanced patient care and improved outcomes.

INTRODUCTION

Excluding skin cancer, prostate cancer is the most common malignancy affecting men in the United States, accounting for ~33% of VA cancer cases. Androgen deprivation therapy (ADT) is considered standard of care in treating advanced prostate cancer. Pituitary apoplexy is a rare and morbid adverse event associated with GnRH agonist treatment. We describe a patient with advanced prostate cancer who developed pituitary apoplexy shortly after leuprolide therapy.

CASE PRESENTATION

A 70-year-old African-American male was diagnosed with a T2aN1M1 stage IVB prostate cancer, Gleason 4+5, PSA 19.5. Four hours after his first leuprolide injection, he developed vomiting, diaphoresis, myalgia, and a severe frontal headache. Brain MRI revealed a 2.4 × 1.3 × 1.3cm pituitary mass, suspicious for an adenoma with hemorrhage. Labs noted low TSH, prolactin, LH, growth hormone, ACTH, cortisol, and testosterone, consistent with pituitary apoplexy. He was treated with steroids. Three weeks later, testosterone levels remained very low. He started abiraterone and prednisone without further leuprolide.

DISCUSSION

Prostate cancer is ubiquitous among VA patients, and ADT with GnRH agonist is vital in their care. These medications stimulate the pituitary to release LH and FSH resulting in a negative feedback loop, ultimately decreasing the levels of testosterone. Common side effects of GnRH agonists include hot flashes, diaphoresis, and sexual dysfunction. We present a patient who started leuprolide for prostate cancer. Symptoms including a severe headache led to an evaluation confirming pituitary apoplexy. Literature review reveals ~ 21 cases of pituitary apoplexy associated with GnRH agonist treatment for prostate cancer, and apoplexy can occur immediately to months later Undiagnosed pituitary adenomas are common among these patients. Treatment includes pituitary surgery or conservative management. Further prostate cancer treatment needs investigation, but we propose that GnRH modifying treatment can be withheld while testosterone levels remain low.

CONCLUSIONS

Prostate cancer is extremely common in the VA population, and treatment with leuprolide is standard. Pituitary apoplexy is a rare, but devastating complication of this treatment, and providers should be aware of the symptoms in order to intervene quickly. Further testosterone lowering treatment may be withheld if testosterone levels remain low.

INTRODUCTION

Excluding skin cancer, prostate cancer is the most common malignancy affecting men in the United States, accounting for ~33% of VA cancer cases. Androgen deprivation therapy (ADT) is considered standard of care in treating advanced prostate cancer. Pituitary apoplexy is a rare and morbid adverse event associated with GnRH agonist treatment. We describe a patient with advanced prostate cancer who developed pituitary apoplexy shortly after leuprolide therapy.

CASE PRESENTATION

A 70-year-old African-American male was diagnosed with a T2aN1M1 stage IVB prostate cancer, Gleason 4+5, PSA 19.5. Four hours after his first leuprolide injection, he developed vomiting, diaphoresis, myalgia, and a severe frontal headache. Brain MRI revealed a 2.4 × 1.3 × 1.3cm pituitary mass, suspicious for an adenoma with hemorrhage. Labs noted low TSH, prolactin, LH, growth hormone, ACTH, cortisol, and testosterone, consistent with pituitary apoplexy. He was treated with steroids. Three weeks later, testosterone levels remained very low. He started abiraterone and prednisone without further leuprolide.

DISCUSSION

Prostate cancer is ubiquitous among VA patients, and ADT with GnRH agonist is vital in their care. These medications stimulate the pituitary to release LH and FSH resulting in a negative feedback loop, ultimately decreasing the levels of testosterone. Common side effects of GnRH agonists include hot flashes, diaphoresis, and sexual dysfunction. We present a patient who started leuprolide for prostate cancer. Symptoms including a severe headache led to an evaluation confirming pituitary apoplexy. Literature review reveals ~ 21 cases of pituitary apoplexy associated with GnRH agonist treatment for prostate cancer, and apoplexy can occur immediately to months later Undiagnosed pituitary adenomas are common among these patients. Treatment includes pituitary surgery or conservative management. Further prostate cancer treatment needs investigation, but we propose that GnRH modifying treatment can be withheld while testosterone levels remain low.

CONCLUSIONS

Prostate cancer is extremely common in the VA population, and treatment with leuprolide is standard. Pituitary apoplexy is a rare, but devastating complication of this treatment, and providers should be aware of the symptoms in order to intervene quickly. Further testosterone lowering treatment may be withheld if testosterone levels remain low.

INTRODUCTION

Excluding skin cancer, prostate cancer is the most common malignancy affecting men in the United States, accounting for ~33% of VA cancer cases. Androgen deprivation therapy (ADT) is considered standard of care in treating advanced prostate cancer. Pituitary apoplexy is a rare and morbid adverse event associated with GnRH agonist treatment. We describe a patient with advanced prostate cancer who developed pituitary apoplexy shortly after leuprolide therapy.

CASE PRESENTATION

A 70-year-old African-American male was diagnosed with a T2aN1M1 stage IVB prostate cancer, Gleason 4+5, PSA 19.5. Four hours after his first leuprolide injection, he developed vomiting, diaphoresis, myalgia, and a severe frontal headache. Brain MRI revealed a 2.4 × 1.3 × 1.3cm pituitary mass, suspicious for an adenoma with hemorrhage. Labs noted low TSH, prolactin, LH, growth hormone, ACTH, cortisol, and testosterone, consistent with pituitary apoplexy. He was treated with steroids. Three weeks later, testosterone levels remained very low. He started abiraterone and prednisone without further leuprolide.

DISCUSSION

Prostate cancer is ubiquitous among VA patients, and ADT with GnRH agonist is vital in their care. These medications stimulate the pituitary to release LH and FSH resulting in a negative feedback loop, ultimately decreasing the levels of testosterone. Common side effects of GnRH agonists include hot flashes, diaphoresis, and sexual dysfunction. We present a patient who started leuprolide for prostate cancer. Symptoms including a severe headache led to an evaluation confirming pituitary apoplexy. Literature review reveals ~ 21 cases of pituitary apoplexy associated with GnRH agonist treatment for prostate cancer, and apoplexy can occur immediately to months later Undiagnosed pituitary adenomas are common among these patients. Treatment includes pituitary surgery or conservative management. Further prostate cancer treatment needs investigation, but we propose that GnRH modifying treatment can be withheld while testosterone levels remain low.

CONCLUSIONS

Prostate cancer is extremely common in the VA population, and treatment with leuprolide is standard. Pituitary apoplexy is a rare, but devastating complication of this treatment, and providers should be aware of the symptoms in order to intervene quickly. Further testosterone lowering treatment may be withheld if testosterone levels remain low.