News

Metabolic modulation may represent a viable therapeutic strategy in pulmonary hypertension (PH), report researchers from the Veterans Affairs Atlanta Healthcare System. Metformin and thiazolidinedione (TZD) were associated with significantly improved survival in their recent retrospective study of 41,670 veterans with PH and diabetes mellitus (DM). Insulin, on the other hand, was associated with increased mortality.

PH is a complex condition that may combine pulmonary vascular disease, heart disease, lung disease, and chronic thromboembolism. More than one-third of veterans with PH also have DM. Veterans are more likely than nonveterans to have chronic cardiopulmonary disease, which may make them particularly susceptible to PH. Moreover, those who served in Iraq and Afghanistan may have respiratory issues that predispose them to PH.

Another study from the same researchers assessed the influence of DM and weight, both potentially modifiable risk factors, on PH outcomes in 110,495 veterans. Veterans with PH survived an average of 3.9 years after PH diagnosis. Roughly one-third had DM, which increased risk of death by 31%. The analysis showed that lower weight and DM were strong risk factors for mortality in PH.

The most striking finding in the current study, according to the researchers, was a consistent reduction of about 20% in mortality risk associated with metformin and a similar association of 18% lower risk with TZD. The contrast with the 28% higher mortality with insulin “likely reflects fundamental differences” in how these medications influence cellular energy metabolism, they reported.

Interactions were observed between drug effects and both renal function and PH comorbidities, with metformin's protective effect enhanced in patients with lower estimated glomerular filtration rate but attenuated in those with lung disease. The associations remained “robust across multiple analytical approaches,” the researchers note.

Hemoglobin A_1c was not associated with outcome, suggesting that these therapies' association with outcome may be irrespective of their glycemic effects. The researchers say this emphasizes the complex interplay between DM and PH pathobiology, known differences in mechanisms of action of antidiabetic medications, and potentially off target impacts of these metabolically active therapies.

Metabolic modulation may represent a viable therapeutic strategy in pulmonary hypertension (PH), report researchers from the Veterans Affairs Atlanta Healthcare System. Metformin and thiazolidinedione (TZD) were associated with significantly improved survival in their recent retrospective study of 41,670 veterans with PH and diabetes mellitus (DM). Insulin, on the other hand, was associated with increased mortality.

PH is a complex condition that may combine pulmonary vascular disease, heart disease, lung disease, and chronic thromboembolism. More than one-third of veterans with PH also have DM. Veterans are more likely than nonveterans to have chronic cardiopulmonary disease, which may make them particularly susceptible to PH. Moreover, those who served in Iraq and Afghanistan may have respiratory issues that predispose them to PH.

Another study from the same researchers assessed the influence of DM and weight, both potentially modifiable risk factors, on PH outcomes in 110,495 veterans. Veterans with PH survived an average of 3.9 years after PH diagnosis. Roughly one-third had DM, which increased risk of death by 31%. The analysis showed that lower weight and DM were strong risk factors for mortality in PH.

The most striking finding in the current study, according to the researchers, was a consistent reduction of about 20% in mortality risk associated with metformin and a similar association of 18% lower risk with TZD. The contrast with the 28% higher mortality with insulin “likely reflects fundamental differences” in how these medications influence cellular energy metabolism, they reported.

Interactions were observed between drug effects and both renal function and PH comorbidities, with metformin's protective effect enhanced in patients with lower estimated glomerular filtration rate but attenuated in those with lung disease. The associations remained “robust across multiple analytical approaches,” the researchers note.

Hemoglobin A_1c was not associated with outcome, suggesting that these therapies' association with outcome may be irrespective of their glycemic effects. The researchers say this emphasizes the complex interplay between DM and PH pathobiology, known differences in mechanisms of action of antidiabetic medications, and potentially off target impacts of these metabolically active therapies.

Metabolic modulation may represent a viable therapeutic strategy in pulmonary hypertension (PH), report researchers from the Veterans Affairs Atlanta Healthcare System. Metformin and thiazolidinedione (TZD) were associated with significantly improved survival in their recent retrospective study of 41,670 veterans with PH and diabetes mellitus (DM). Insulin, on the other hand, was associated with increased mortality.

PH is a complex condition that may combine pulmonary vascular disease, heart disease, lung disease, and chronic thromboembolism. More than one-third of veterans with PH also have DM. Veterans are more likely than nonveterans to have chronic cardiopulmonary disease, which may make them particularly susceptible to PH. Moreover, those who served in Iraq and Afghanistan may have respiratory issues that predispose them to PH.

Another study from the same researchers assessed the influence of DM and weight, both potentially modifiable risk factors, on PH outcomes in 110,495 veterans. Veterans with PH survived an average of 3.9 years after PH diagnosis. Roughly one-third had DM, which increased risk of death by 31%. The analysis showed that lower weight and DM were strong risk factors for mortality in PH.

The most striking finding in the current study, according to the researchers, was a consistent reduction of about 20% in mortality risk associated with metformin and a similar association of 18% lower risk with TZD. The contrast with the 28% higher mortality with insulin “likely reflects fundamental differences” in how these medications influence cellular energy metabolism, they reported.

Interactions were observed between drug effects and both renal function and PH comorbidities, with metformin's protective effect enhanced in patients with lower estimated glomerular filtration rate but attenuated in those with lung disease. The associations remained “robust across multiple analytical approaches,” the researchers note.

Hemoglobin A_1c was not associated with outcome, suggesting that these therapies' association with outcome may be irrespective of their glycemic effects. The researchers say this emphasizes the complex interplay between DM and PH pathobiology, known differences in mechanisms of action of antidiabetic medications, and potentially off target impacts of these metabolically active therapies.

A novel wearable wrist device was feasible and effective for identifying exposure to respiratory viruses in children with asthma, based on new data presented at the American Thoracic Society 2026 International Conference.

Upper respiratory infections are the main trigger of asthma exacerbations in children, and documented racial and ethnic disparities in upper respiratory infections likely contribute to similar disparities in asthma exacerbations, noted Darlene Bhavnani, PhD, MPH, of The University of Texas at Austin, et al in their abstract.

“Understanding differences in personal exposure to upper respiratory viruses in children with asthma may help to inform these differences in the risk of viral infection and viral-associated asthma exacerbations,” Bhavnani said.

The researchers hypothesized that the use of a wearable passive air sampler could monitor respiratory virus exposure as a way to identify children at increased risk for asthma exacerbations.

Wrist devices to measure respiratory virus exposure are an emerging technology and have not been tested in children, the researchers noted. In their study, the researchers identified 25 children aged 6 to 17 years with persistent asthma who were enrolled in the TexHALE study. Participants were given a Fresh Air Clip to station in their homes and were asked to wear a wristband with a Fresh Air Clip for about 5 consecutive days. The median age of the participants was 12 years, and 64% were male.

At the end of the study period, families reported the number of days the wristband was worn, and the researchers used droplet digital polymerase chain reaction tests to quantify exposure to rhinovirus, respiratory syncytial virus (RSV), influenza A, and influenza B.

A total of 24 clips and 24 wristbands were distributed; 23 clips and all 24 wristbands were recovered for analysis. A total of 22 participants (92%) wore the wristband over a median of 6 days. Overall, approximately one-third of the wristbands (33%) tested positive for any respiratory virus, defined as > 6 copies of viral RNA, with 5 positive tests for rhinovirus, 5 for influenza B, 2 for RSV, and none for influenza A. None of the stationary home-based clips tested positive for any respiratory virus.

The researchers were not sure what to expect from the study, as personal exposure to upper respiratory viruses has not been well studied in children, said Bhavnani.

“One third of the children in our pilot study were exposed to one or more upper respiratory viruses in their personal environments, which is a substantial portion of the population studied,” she noted. “Given that viral exposure is the first step in the pathway leading to a viral infection and viral-associated asthma exacerbations, understanding differences in viral exposure could help us to learn more about how to prevent viral infection and viral-associated asthma exacerbations in children with asthma,” she said.

The study was limited by the small sample size, and larger studies are needed. However, the finding the one-third of wristbands and zero stationary clips tested positive for upper respiratory viruses suggests that clips stationed in homes may not be optimal to detect household exposures, or and that exposure outside the home may be more important for monitoring exposure to respiratory viruses in this population, and the results support the feasibility of the devices, the researchers wrote.

“Fresh Air Clips in the form of wearables can be used to understand differences in personal viral exposure and to target interventions that ultimately, would reduce the burden of viral infection and viral-associated asthma exacerbations,” Bhavnani said.

New Role for New Technology

“New technology now allows us to quantitate exposure to specific respiratory viruses on wearable and stationary devices,” said Tim Joos, MD, who practices internal medicine and pediatrics at a community health center in Seattle.

The current study findings suggest that the majority of the exposure to respiratory viruses occurs outside the home, said Joos, who was not involved in the study. Consequently, technology that can detect community exposure could be useful, although the role it may play in public health and clinical practice is yet to be determined, Joos said.

The wristbands and clips were easy to deploy and recover, which supports their value, and potential applications include testing the effectiveness of infection control strategies such as social distancing, masking, and isolation in lowering viral exposures, Joos noted.

The study received no outside funding but was supported by core funds from the Dell Medical School at the University of Texas at Austin. The researchers had no financial conflicts to disclose. Joos had no financial conflicts to disclose.

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

A novel wearable wrist device was feasible and effective for identifying exposure to respiratory viruses in children with asthma, based on new data presented at the American Thoracic Society 2026 International Conference.

Upper respiratory infections are the main trigger of asthma exacerbations in children, and documented racial and ethnic disparities in upper respiratory infections likely contribute to similar disparities in asthma exacerbations, noted Darlene Bhavnani, PhD, MPH, of The University of Texas at Austin, et al in their abstract.

“Understanding differences in personal exposure to upper respiratory viruses in children with asthma may help to inform these differences in the risk of viral infection and viral-associated asthma exacerbations,” Bhavnani said.

The researchers hypothesized that the use of a wearable passive air sampler could monitor respiratory virus exposure as a way to identify children at increased risk for asthma exacerbations.

Wrist devices to measure respiratory virus exposure are an emerging technology and have not been tested in children, the researchers noted. In their study, the researchers identified 25 children aged 6 to 17 years with persistent asthma who were enrolled in the TexHALE study. Participants were given a Fresh Air Clip to station in their homes and were asked to wear a wristband with a Fresh Air Clip for about 5 consecutive days. The median age of the participants was 12 years, and 64% were male.

At the end of the study period, families reported the number of days the wristband was worn, and the researchers used droplet digital polymerase chain reaction tests to quantify exposure to rhinovirus, respiratory syncytial virus (RSV), influenza A, and influenza B.

A total of 24 clips and 24 wristbands were distributed; 23 clips and all 24 wristbands were recovered for analysis. A total of 22 participants (92%) wore the wristband over a median of 6 days. Overall, approximately one-third of the wristbands (33%) tested positive for any respiratory virus, defined as > 6 copies of viral RNA, with 5 positive tests for rhinovirus, 5 for influenza B, 2 for RSV, and none for influenza A. None of the stationary home-based clips tested positive for any respiratory virus.

The researchers were not sure what to expect from the study, as personal exposure to upper respiratory viruses has not been well studied in children, said Bhavnani.

“One third of the children in our pilot study were exposed to one or more upper respiratory viruses in their personal environments, which is a substantial portion of the population studied,” she noted. “Given that viral exposure is the first step in the pathway leading to a viral infection and viral-associated asthma exacerbations, understanding differences in viral exposure could help us to learn more about how to prevent viral infection and viral-associated asthma exacerbations in children with asthma,” she said.

The study was limited by the small sample size, and larger studies are needed. However, the finding the one-third of wristbands and zero stationary clips tested positive for upper respiratory viruses suggests that clips stationed in homes may not be optimal to detect household exposures, or and that exposure outside the home may be more important for monitoring exposure to respiratory viruses in this population, and the results support the feasibility of the devices, the researchers wrote.

“Fresh Air Clips in the form of wearables can be used to understand differences in personal viral exposure and to target interventions that ultimately, would reduce the burden of viral infection and viral-associated asthma exacerbations,” Bhavnani said.

New Role for New Technology

“New technology now allows us to quantitate exposure to specific respiratory viruses on wearable and stationary devices,” said Tim Joos, MD, who practices internal medicine and pediatrics at a community health center in Seattle.

The current study findings suggest that the majority of the exposure to respiratory viruses occurs outside the home, said Joos, who was not involved in the study. Consequently, technology that can detect community exposure could be useful, although the role it may play in public health and clinical practice is yet to be determined, Joos said.

The wristbands and clips were easy to deploy and recover, which supports their value, and potential applications include testing the effectiveness of infection control strategies such as social distancing, masking, and isolation in lowering viral exposures, Joos noted.

The study received no outside funding but was supported by core funds from the Dell Medical School at the University of Texas at Austin. The researchers had no financial conflicts to disclose. Joos had no financial conflicts to disclose.

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

A novel wearable wrist device was feasible and effective for identifying exposure to respiratory viruses in children with asthma, based on new data presented at the American Thoracic Society 2026 International Conference.

Upper respiratory infections are the main trigger of asthma exacerbations in children, and documented racial and ethnic disparities in upper respiratory infections likely contribute to similar disparities in asthma exacerbations, noted Darlene Bhavnani, PhD, MPH, of The University of Texas at Austin, et al in their abstract.

“Understanding differences in personal exposure to upper respiratory viruses in children with asthma may help to inform these differences in the risk of viral infection and viral-associated asthma exacerbations,” Bhavnani said.

The researchers hypothesized that the use of a wearable passive air sampler could monitor respiratory virus exposure as a way to identify children at increased risk for asthma exacerbations.

Wrist devices to measure respiratory virus exposure are an emerging technology and have not been tested in children, the researchers noted. In their study, the researchers identified 25 children aged 6 to 17 years with persistent asthma who were enrolled in the TexHALE study. Participants were given a Fresh Air Clip to station in their homes and were asked to wear a wristband with a Fresh Air Clip for about 5 consecutive days. The median age of the participants was 12 years, and 64% were male.

At the end of the study period, families reported the number of days the wristband was worn, and the researchers used droplet digital polymerase chain reaction tests to quantify exposure to rhinovirus, respiratory syncytial virus (RSV), influenza A, and influenza B.

A total of 24 clips and 24 wristbands were distributed; 23 clips and all 24 wristbands were recovered for analysis. A total of 22 participants (92%) wore the wristband over a median of 6 days. Overall, approximately one-third of the wristbands (33%) tested positive for any respiratory virus, defined as > 6 copies of viral RNA, with 5 positive tests for rhinovirus, 5 for influenza B, 2 for RSV, and none for influenza A. None of the stationary home-based clips tested positive for any respiratory virus.

The researchers were not sure what to expect from the study, as personal exposure to upper respiratory viruses has not been well studied in children, said Bhavnani.

“One third of the children in our pilot study were exposed to one or more upper respiratory viruses in their personal environments, which is a substantial portion of the population studied,” she noted. “Given that viral exposure is the first step in the pathway leading to a viral infection and viral-associated asthma exacerbations, understanding differences in viral exposure could help us to learn more about how to prevent viral infection and viral-associated asthma exacerbations in children with asthma,” she said.

The study was limited by the small sample size, and larger studies are needed. However, the finding the one-third of wristbands and zero stationary clips tested positive for upper respiratory viruses suggests that clips stationed in homes may not be optimal to detect household exposures, or and that exposure outside the home may be more important for monitoring exposure to respiratory viruses in this population, and the results support the feasibility of the devices, the researchers wrote.

“Fresh Air Clips in the form of wearables can be used to understand differences in personal viral exposure and to target interventions that ultimately, would reduce the burden of viral infection and viral-associated asthma exacerbations,” Bhavnani said.

New Role for New Technology

“New technology now allows us to quantitate exposure to specific respiratory viruses on wearable and stationary devices,” said Tim Joos, MD, who practices internal medicine and pediatrics at a community health center in Seattle.

The current study findings suggest that the majority of the exposure to respiratory viruses occurs outside the home, said Joos, who was not involved in the study. Consequently, technology that can detect community exposure could be useful, although the role it may play in public health and clinical practice is yet to be determined, Joos said.

The wristbands and clips were easy to deploy and recover, which supports their value, and potential applications include testing the effectiveness of infection control strategies such as social distancing, masking, and isolation in lowering viral exposures, Joos noted.

The study received no outside funding but was supported by core funds from the Dell Medical School at the University of Texas at Austin. The researchers had no financial conflicts to disclose. Joos had no financial conflicts to disclose.

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

Disruptions caused by the COVID-19 pandemic led to an estimated 619 missed cases of colorectal cancer (CRC) diagnoses among US veterans, and those whose cases were caught had larger tumors and more malignant bowel obstructions compared with a prepandemic period, a new longitudinal study finds.

The decline in diagnoses during the pandemic (March 2020-October 2023) represented a 5% decrease in anticipated cases compared with the prepandemic period (January 2017-February 2020) reported Veterans Health Administration (VHA) researchers in the Journal of Gastrointestinal Surgery.

Meanwhile, the percentage of cancers > 4 cm increased from 48.9% to 57.3% from the prepandemic to pandemic periods, and the percentage of patients with malignant bowel obstructions at presentation nearly doubled from 2.7% to 5.3%. 

“The COVID-19 pandemic resulted in a significant initial decrease in rates of colon cancer diagnosis, with a slow return to baseline,” Louise Davies, MD, MS, a head-and-neck surgeon at the University of Wisconsin-Madison and senior author of the study told Federal Practitioner. “The length of time it took for things to return to normal surprised us. Patterns of detection did not return to more normal baselines until 2023.”

The Pandemic’s Toll on Colonoscopies

While mortality and diagnosis rates have fallen significantly over the past 3 decades, an estimated 158,850 colorectal cancer cases will be diagnosed in the US in 2026, and 55,230 patients will die. Within the VHA, an estimated 4000 new cases of colorectal cancer are diagnosed annually. 

The pandemic disrupted medical care across the board, and colonoscopies were no exceptions. “There are various estimates that there were anywhere from 2 to 3 million missed exams,” said Timothy Pawlik, MD, PhD, MBA, MPH, a surgical oncologist and professor at The Ohio State University Wexner Medical Center, in an interview. 

“At the height of the pandemic, all nonurgent procedures were put on hold,” explained Pawlik, who was not involved in the new study. “I suspect that a number of procedures were missed because different institutions and GI practices simply weren't providing that service at that time. In addition, I'm sure there was some reticence among patients to seek care even after the procedures were restarted and reoffered, especially at a hospital.”

Inside the VHA Data

The researchers found that 22,256 VHA patients were diagnosed with CRC during the study period (mean age, 71 years; 95.6% male; 72.1% White, 19.3% Black, and 6.4% Hispanic). 

In a subset of 1087 patients, the percentage with an American Society of Anesthesiologists class ≥ 3 rose from 74.4% before the pandemic to 78.9% during it. 

In light of the study findings, “clinicians should encourage their eligible patients to get screened for colon cancer, especially if they delayed screening as a result of the pandemic,” Davies said. 

Why Colonoscopy Delays Matter

Pawlik, the Ohio State University Wexner Medical Center surgical oncologist, said even small delays in colonoscopies can be important. 

“There are data suggesting that even a delay beyond 6 to 12 months can significantly increase the risk of advanced-stage cancer. Longer delays of a year, which were associated with the pandemic, definitely increase the risk of presenting with later stages of disease and potentially have a meaningful impact on your prognosis and survival.”

However, he noted that the study findings are limited because the results don’t clarify when patients were due for colonoscopies. 

Still, in the big picture, the research “emphasizes the importance of timely colonoscopy compliance with national guidelines for screening of colon cancer,” he said. 

Lessons About At-Home Tests

Pawlik added that the research also highlights that in times of limited access such as pandemics, there can be value to pivoting to home-based screening methods.

Study coauthor Douglas Robertson, MD, MPH, national deputy director of the Colorectal Cancer Screening Program with the US Department of Veterans Affairs National Gastroenterology and Hepatology Program, said the pandemic spurred a shift toward fecal immunochemical testing (FIT) via mail. 

The VA is now mailing > 40,000 FIT tests per month to veterans. “This program was an outgrowth of and response to the pandemic and would enhance VA’s readiness to maintain CRC screening efforts should something similar occur in the future,” Robertson said in an interview.

The Department of Veterans Affairs funded the study. Davies, Robertson, and the other study authors have no disclosures. Pawlik is co-editor-in-chief of the Journal of Gastrointestinal Surgery and has no other disclosures. 

Disruptions caused by the COVID-19 pandemic led to an estimated 619 missed cases of colorectal cancer (CRC) diagnoses among US veterans, and those whose cases were caught had larger tumors and more malignant bowel obstructions compared with a prepandemic period, a new longitudinal study finds.

The decline in diagnoses during the pandemic (March 2020-October 2023) represented a 5% decrease in anticipated cases compared with the prepandemic period (January 2017-February 2020) reported Veterans Health Administration (VHA) researchers in the Journal of Gastrointestinal Surgery.

Meanwhile, the percentage of cancers > 4 cm increased from 48.9% to 57.3% from the prepandemic to pandemic periods, and the percentage of patients with malignant bowel obstructions at presentation nearly doubled from 2.7% to 5.3%. 

“The COVID-19 pandemic resulted in a significant initial decrease in rates of colon cancer diagnosis, with a slow return to baseline,” Louise Davies, MD, MS, a head-and-neck surgeon at the University of Wisconsin-Madison and senior author of the study told Federal Practitioner. “The length of time it took for things to return to normal surprised us. Patterns of detection did not return to more normal baselines until 2023.”

The Pandemic’s Toll on Colonoscopies

While mortality and diagnosis rates have fallen significantly over the past 3 decades, an estimated 158,850 colorectal cancer cases will be diagnosed in the US in 2026, and 55,230 patients will die. Within the VHA, an estimated 4000 new cases of colorectal cancer are diagnosed annually. 

The pandemic disrupted medical care across the board, and colonoscopies were no exceptions. “There are various estimates that there were anywhere from 2 to 3 million missed exams,” said Timothy Pawlik, MD, PhD, MBA, MPH, a surgical oncologist and professor at The Ohio State University Wexner Medical Center, in an interview. 

“At the height of the pandemic, all nonurgent procedures were put on hold,” explained Pawlik, who was not involved in the new study. “I suspect that a number of procedures were missed because different institutions and GI practices simply weren't providing that service at that time. In addition, I'm sure there was some reticence among patients to seek care even after the procedures were restarted and reoffered, especially at a hospital.”

Inside the VHA Data

The researchers found that 22,256 VHA patients were diagnosed with CRC during the study period (mean age, 71 years; 95.6% male; 72.1% White, 19.3% Black, and 6.4% Hispanic). 

In a subset of 1087 patients, the percentage with an American Society of Anesthesiologists class ≥ 3 rose from 74.4% before the pandemic to 78.9% during it. 

In light of the study findings, “clinicians should encourage their eligible patients to get screened for colon cancer, especially if they delayed screening as a result of the pandemic,” Davies said. 

Why Colonoscopy Delays Matter

Pawlik, the Ohio State University Wexner Medical Center surgical oncologist, said even small delays in colonoscopies can be important. 

“There are data suggesting that even a delay beyond 6 to 12 months can significantly increase the risk of advanced-stage cancer. Longer delays of a year, which were associated with the pandemic, definitely increase the risk of presenting with later stages of disease and potentially have a meaningful impact on your prognosis and survival.”

However, he noted that the study findings are limited because the results don’t clarify when patients were due for colonoscopies. 

Still, in the big picture, the research “emphasizes the importance of timely colonoscopy compliance with national guidelines for screening of colon cancer,” he said. 

Lessons About At-Home Tests

Pawlik added that the research also highlights that in times of limited access such as pandemics, there can be value to pivoting to home-based screening methods.

Study coauthor Douglas Robertson, MD, MPH, national deputy director of the Colorectal Cancer Screening Program with the US Department of Veterans Affairs National Gastroenterology and Hepatology Program, said the pandemic spurred a shift toward fecal immunochemical testing (FIT) via mail. 

The VA is now mailing > 40,000 FIT tests per month to veterans. “This program was an outgrowth of and response to the pandemic and would enhance VA’s readiness to maintain CRC screening efforts should something similar occur in the future,” Robertson said in an interview.

The Department of Veterans Affairs funded the study. Davies, Robertson, and the other study authors have no disclosures. Pawlik is co-editor-in-chief of the Journal of Gastrointestinal Surgery and has no other disclosures. 

Disruptions caused by the COVID-19 pandemic led to an estimated 619 missed cases of colorectal cancer (CRC) diagnoses among US veterans, and those whose cases were caught had larger tumors and more malignant bowel obstructions compared with a prepandemic period, a new longitudinal study finds.

The decline in diagnoses during the pandemic (March 2020-October 2023) represented a 5% decrease in anticipated cases compared with the prepandemic period (January 2017-February 2020) reported Veterans Health Administration (VHA) researchers in the Journal of Gastrointestinal Surgery.

Meanwhile, the percentage of cancers > 4 cm increased from 48.9% to 57.3% from the prepandemic to pandemic periods, and the percentage of patients with malignant bowel obstructions at presentation nearly doubled from 2.7% to 5.3%. 

“The COVID-19 pandemic resulted in a significant initial decrease in rates of colon cancer diagnosis, with a slow return to baseline,” Louise Davies, MD, MS, a head-and-neck surgeon at the University of Wisconsin-Madison and senior author of the study told Federal Practitioner. “The length of time it took for things to return to normal surprised us. Patterns of detection did not return to more normal baselines until 2023.”

The Pandemic’s Toll on Colonoscopies

While mortality and diagnosis rates have fallen significantly over the past 3 decades, an estimated 158,850 colorectal cancer cases will be diagnosed in the US in 2026, and 55,230 patients will die. Within the VHA, an estimated 4000 new cases of colorectal cancer are diagnosed annually. 

The pandemic disrupted medical care across the board, and colonoscopies were no exceptions. “There are various estimates that there were anywhere from 2 to 3 million missed exams,” said Timothy Pawlik, MD, PhD, MBA, MPH, a surgical oncologist and professor at The Ohio State University Wexner Medical Center, in an interview. 

“At the height of the pandemic, all nonurgent procedures were put on hold,” explained Pawlik, who was not involved in the new study. “I suspect that a number of procedures were missed because different institutions and GI practices simply weren't providing that service at that time. In addition, I'm sure there was some reticence among patients to seek care even after the procedures were restarted and reoffered, especially at a hospital.”

Inside the VHA Data

The researchers found that 22,256 VHA patients were diagnosed with CRC during the study period (mean age, 71 years; 95.6% male; 72.1% White, 19.3% Black, and 6.4% Hispanic). 

In a subset of 1087 patients, the percentage with an American Society of Anesthesiologists class ≥ 3 rose from 74.4% before the pandemic to 78.9% during it. 

In light of the study findings, “clinicians should encourage their eligible patients to get screened for colon cancer, especially if they delayed screening as a result of the pandemic,” Davies said. 

Why Colonoscopy Delays Matter

Pawlik, the Ohio State University Wexner Medical Center surgical oncologist, said even small delays in colonoscopies can be important. 

“There are data suggesting that even a delay beyond 6 to 12 months can significantly increase the risk of advanced-stage cancer. Longer delays of a year, which were associated with the pandemic, definitely increase the risk of presenting with later stages of disease and potentially have a meaningful impact on your prognosis and survival.”

However, he noted that the study findings are limited because the results don’t clarify when patients were due for colonoscopies. 

Still, in the big picture, the research “emphasizes the importance of timely colonoscopy compliance with national guidelines for screening of colon cancer,” he said. 

Lessons About At-Home Tests

Pawlik added that the research also highlights that in times of limited access such as pandemics, there can be value to pivoting to home-based screening methods.

Study coauthor Douglas Robertson, MD, MPH, national deputy director of the Colorectal Cancer Screening Program with the US Department of Veterans Affairs National Gastroenterology and Hepatology Program, said the pandemic spurred a shift toward fecal immunochemical testing (FIT) via mail. 

The VA is now mailing > 40,000 FIT tests per month to veterans. “This program was an outgrowth of and response to the pandemic and would enhance VA’s readiness to maintain CRC screening efforts should something similar occur in the future,” Robertson said in an interview.

The Department of Veterans Affairs funded the study. Davies, Robertson, and the other study authors have no disclosures. Pawlik is co-editor-in-chief of the Journal of Gastrointestinal Surgery and has no other disclosures. 

TOPLINE:

In a population-based study, human papillomavirus (HPV) vaccination in England was associated with a 100% reduction in mortality due to cervical cancer between 2020 and 2024 among women aged 20-24 years who were mostly vaccinated at the age of 12-13 years.

METHODOLOGY:

• Researchers conducted a population-based study using cervical cancer mortality data of women aged 20-24, 25-29, and 30-34 years from the National Disease Registration Service and Office for National Statistics in England from 2000 to 2024.
• The analysis included women from the first eligible birth cohort (born from September 1990 to August 1991) who were targeted by England's school-based HPV vaccination programme introduced in September 2008 for girls aged 12-13 years, with a catch-up programme for girls aged 14-18 years implemented in 2008-2010.
• HPV vaccination coverage by birth cohort was obtained from annual reports of the UK Health Security Agency and used to estimate the proportion of women vaccinated for each age group and calendar year.
• The relative risk reduction (RRR) in mortality among vaccinated women compared with expected rates in the absence of vaccination, assuming no herd immunity, was evaluated.

TAKEAWAY:

• Among women aged 20-24 years between 2020 and 2024 with approximately 88%-91% vaccination coverage, no deaths occurred compared with 23.1 expected deaths on the basis of the observed average rate from 2000 to 2014, corresponding to a reduction in mortality of 100% (95% CI, 84%-100%).
• Among vaccinated women, the RRR in mortality due to cervical cancer was estimated at 100% (P = .0008) in those aged 20-24 years, 100% (P < .0001) in those aged 25-29 years, and 63% (P = .094) in those aged 30-34 years.
• Mortality reductions of 80% (95% CI, 51%-94%) were observed in women aged 20-24 years during 2015-2019 and 69% (95% CI, 55%-79%) were observed in those aged 25-29 years during 2020-2024.
• Up until the end of 2024, the HPV vaccination programme in England was associated with a reduction of approximately 199.6 deaths due to cervical cancer (95% CI, 125.0-274.2) among cohorts offered vaccination.

IN PRACTICE:

The authors concluded that "we found a substantial reduction in cervical cancer mortality in women aged 20-29 years that was associated with high uptake of HPV vaccination." "This observation further supports the benefit of HPV vaccination in reducing not only the incidence of but also the mortality from a cancer that is globally still the second most common cause of cancer death in women younger than 65 years," they added. SOURCE: The study was led by Peter Sasieni, PhD, Centre for Cancer Screening, Prevention and Early Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, London, England. It was published online on June 17, 2026, in The Lancet.

LIMITATIONS:

The analysis relied on population-level vaccination coverage data instead of individual-level status; the researchers had access to mortality data in 5-year age groups only rather than single-year cohorts, and the study assumed no herd protection among unvaccinated women within birth cohorts.

DISCLOSURES:

The study was funded by the Cancer Research UK. One author reported serving as a lead investigator of a trial examining the HPV vaccine Gardasil 9 that was partially supported by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme. Additional disclosures are listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

In a population-based study, human papillomavirus (HPV) vaccination in England was associated with a 100% reduction in mortality due to cervical cancer between 2020 and 2024 among women aged 20-24 years who were mostly vaccinated at the age of 12-13 years.

METHODOLOGY:

• Researchers conducted a population-based study using cervical cancer mortality data of women aged 20-24, 25-29, and 30-34 years from the National Disease Registration Service and Office for National Statistics in England from 2000 to 2024.
• The analysis included women from the first eligible birth cohort (born from September 1990 to August 1991) who were targeted by England's school-based HPV vaccination programme introduced in September 2008 for girls aged 12-13 years, with a catch-up programme for girls aged 14-18 years implemented in 2008-2010.
• HPV vaccination coverage by birth cohort was obtained from annual reports of the UK Health Security Agency and used to estimate the proportion of women vaccinated for each age group and calendar year.
• The relative risk reduction (RRR) in mortality among vaccinated women compared with expected rates in the absence of vaccination, assuming no herd immunity, was evaluated.

TAKEAWAY:

• Among women aged 20-24 years between 2020 and 2024 with approximately 88%-91% vaccination coverage, no deaths occurred compared with 23.1 expected deaths on the basis of the observed average rate from 2000 to 2014, corresponding to a reduction in mortality of 100% (95% CI, 84%-100%).
• Among vaccinated women, the RRR in mortality due to cervical cancer was estimated at 100% (P = .0008) in those aged 20-24 years, 100% (P < .0001) in those aged 25-29 years, and 63% (P = .094) in those aged 30-34 years.
• Mortality reductions of 80% (95% CI, 51%-94%) were observed in women aged 20-24 years during 2015-2019 and 69% (95% CI, 55%-79%) were observed in those aged 25-29 years during 2020-2024.
• Up until the end of 2024, the HPV vaccination programme in England was associated with a reduction of approximately 199.6 deaths due to cervical cancer (95% CI, 125.0-274.2) among cohorts offered vaccination.

IN PRACTICE:

The authors concluded that "we found a substantial reduction in cervical cancer mortality in women aged 20-29 years that was associated with high uptake of HPV vaccination." "This observation further supports the benefit of HPV vaccination in reducing not only the incidence of but also the mortality from a cancer that is globally still the second most common cause of cancer death in women younger than 65 years," they added. SOURCE: The study was led by Peter Sasieni, PhD, Centre for Cancer Screening, Prevention and Early Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, London, England. It was published online on June 17, 2026, in The Lancet.

LIMITATIONS:

The analysis relied on population-level vaccination coverage data instead of individual-level status; the researchers had access to mortality data in 5-year age groups only rather than single-year cohorts, and the study assumed no herd protection among unvaccinated women within birth cohorts.

DISCLOSURES:

The study was funded by the Cancer Research UK. One author reported serving as a lead investigator of a trial examining the HPV vaccine Gardasil 9 that was partially supported by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme. Additional disclosures are listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

In a population-based study, human papillomavirus (HPV) vaccination in England was associated with a 100% reduction in mortality due to cervical cancer between 2020 and 2024 among women aged 20-24 years who were mostly vaccinated at the age of 12-13 years.

METHODOLOGY:

• Researchers conducted a population-based study using cervical cancer mortality data of women aged 20-24, 25-29, and 30-34 years from the National Disease Registration Service and Office for National Statistics in England from 2000 to 2024.
• The analysis included women from the first eligible birth cohort (born from September 1990 to August 1991) who were targeted by England's school-based HPV vaccination programme introduced in September 2008 for girls aged 12-13 years, with a catch-up programme for girls aged 14-18 years implemented in 2008-2010.
• HPV vaccination coverage by birth cohort was obtained from annual reports of the UK Health Security Agency and used to estimate the proportion of women vaccinated for each age group and calendar year.
• The relative risk reduction (RRR) in mortality among vaccinated women compared with expected rates in the absence of vaccination, assuming no herd immunity, was evaluated.

TAKEAWAY:

• Among women aged 20-24 years between 2020 and 2024 with approximately 88%-91% vaccination coverage, no deaths occurred compared with 23.1 expected deaths on the basis of the observed average rate from 2000 to 2014, corresponding to a reduction in mortality of 100% (95% CI, 84%-100%).
• Among vaccinated women, the RRR in mortality due to cervical cancer was estimated at 100% (P = .0008) in those aged 20-24 years, 100% (P < .0001) in those aged 25-29 years, and 63% (P = .094) in those aged 30-34 years.
• Mortality reductions of 80% (95% CI, 51%-94%) were observed in women aged 20-24 years during 2015-2019 and 69% (95% CI, 55%-79%) were observed in those aged 25-29 years during 2020-2024.
• Up until the end of 2024, the HPV vaccination programme in England was associated with a reduction of approximately 199.6 deaths due to cervical cancer (95% CI, 125.0-274.2) among cohorts offered vaccination.

IN PRACTICE:

The authors concluded that "we found a substantial reduction in cervical cancer mortality in women aged 20-29 years that was associated with high uptake of HPV vaccination." "This observation further supports the benefit of HPV vaccination in reducing not only the incidence of but also the mortality from a cancer that is globally still the second most common cause of cancer death in women younger than 65 years," they added. SOURCE: The study was led by Peter Sasieni, PhD, Centre for Cancer Screening, Prevention and Early Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, London, England. It was published online on June 17, 2026, in The Lancet.

LIMITATIONS:

The analysis relied on population-level vaccination coverage data instead of individual-level status; the researchers had access to mortality data in 5-year age groups only rather than single-year cohorts, and the study assumed no herd protection among unvaccinated women within birth cohorts.

DISCLOSURES:

The study was funded by the Cancer Research UK. One author reported serving as a lead investigator of a trial examining the HPV vaccine Gardasil 9 that was partially supported by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme. Additional disclosures are listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

Rapid-growing nontuberculous mycobacteria (NTM) were strongly associated with death or retransplantation in adult lung transplant patients, based on data from a new study of about 1000 individuals.

NTM are ubiquitous environmental organisms, but the clinical significance of isolating NTM posttransplant remains poorly defined, and previous studies have been mainly small and single center, said lead author Gabrielle Mezochow, MD, a pulmonology and critical care fellow at the University of Pennsylvania in Philadelphia.

“This is important because treatment is particularly challenging in lung transplant recipients, requiring prolonged multidrug regimens that can be toxic and interact with immunosuppression,” Mezochow said. “We conducted this study to better understand how often NTM is isolated after lung transplant, and whether isolation is associated with important outcomes such as chronic lung allograft dysfunction (CLAD) and death or retransplantation in a large multicenter cohort,” she said.

In the study, presented at the annual meeting of the International Society for Heart and Lung Transplantation (ISHLT), Mezochow et al reviewed data from 1044 adult lung transplant recipients in the Lung Transplant Outcomes Group cohort who underwent transplant between 2007 and 2022 at 3 centers.

The researchers evaluated the time from transplantation to graft failure (defined as death or retransplantation) and CLAD (as defined by the ISHLT). They used a proportional hazards model adjusted for age, diagnosis, BMI, primary graft dysfunction, postoperative extracorporeal membrane oxygenation, and transplant type.

A total of 136 patients (13%) had pulmonary growth of NTM within a year of their transplants; the most common types were Mycobacterium avium (88 patients) and Mycobacterium abscessus (16 patients).

Overall, the association between early growth of any NTM and the risk for graft failure did not reach statistical significance (adjusted hazard ratio [HR], 1.27). However, patients who had early growth of rapid-growing NTM (including M abscessus, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium immunogenum, Mycobacterium mageritense, and Mycobacterium mucogenicum) had an increased risk for graft failure compared to those with early growth of slow-growing NTM such as M avium (unadjusted HR, 2.36; adjusted HR, 2.49). The associations were consistent when patients with cystic fibrosis were excluded, and no significant association was observed between early NTM growth by slow or rapid types and increased risk for CLAD (adjusted HR, 1.09).

“One of the most interesting findings was that associations differed by NTM species,” Mezochow said. “Rapid-growing NTM were most strongly associated with death or retransplantation, whereas slow-growing NTM appeared to have a stronger association with CLAD,” she said. “We were also intrigued by the stronger associations with negative outcomes observed among recipients with ILD [interstitial lung disease], particularly those undergoing single lung transplantation,” Mezochow noted. “This raises the possibility that characteristics of the native lung or underlying lung disease may influence susceptibility and outcomes,” she said.

“Importantly, our study evaluated NTM isolation rather than NTM pulmonary disease, which is often difficult to define in lung transplant recipients,” said Mezochow. The results suggest that NTM isolation should not be dismissed as a benign microbiologic finding and could serve as an early marker of lung transplant recipients at increased risk for poor outcomes, even before disease can be definitively established, she noted. “Certain subgroups of recipients, including those with specific NTM species or underlying diagnoses, may be at a particularly elevated risk for poor outcomes, while not all patients with NTM isolation are likely to require treatment,” she added.

Limitations and Next Steps

The findings were limited by several factors including the observational design and lack of detailed patient-level medication data including longitudinal immunosuppression, antibiotic exposures, and azithromycin use for bronchiolitis obliterans syndrome prevention, any of which could influence both NTM isolation and downstream outcomes, Mezochow said.

The researchers also were unable to adjudicate NTM pulmonary disease according to current guideline-based definitions because of the lack of longitudinal radiographic and symptom data, she added. “That said, these diagnostic criteria were developed outside the transplant setting and have not been validated in lung transplant recipients, so their applicability here is uncertain,” she added. “Although we focused on the first posttransplant year, when surveillance bronchoscopy is relatively routine, some residual ascertainment bias is still likely,” she noted.

“Future research should focus on identifying which recipients with NTM isolation are most likely to progress to CLAD or death, understanding the biologic mechanisms linking NTM and allograft injury, and determining whether treatment strategies or immunosuppression modifications can improve outcomes,” said Mezochow. “Ultimately, the goal is to develop a framework that helps clinicians distinguish who may benefit from treatment from those who can be safely observed,” she said.

Added Value for Patient Assessment

The current study addresses major questions in lung transplantation, namely, whether isolation of NTM species in the first year after a lung transplant is a marker of airway vulnerability, structural airway defects, patient frailty, or a true contributor to allograft function and failure, said Jacqueline Burnell, MD, an associate professor of clinical medicine at the Lewis Katz School of Medicine at Temple University in Philadelphia, and a specialist in infections in transplant and immunocompromised patients. “This study separated rapidly growing NTM from slow growers to attempt to identify species associated with poor outcomes and provide prognostication,” said Burnell, who was not involved in the study. The association of rapidly growing NTM and poorer outcomes was not surprising, she noted. “Mycobacterium abscessus species, which accounted for the majority of rapidly growing isolates, are thought to be more aggressive and are certainly more challenging to treat,” she said. “The absence of association with CLAD is interesting, as this has been found in other studies looking at NTM infections post-lung transplant,” she added.

The results suggest that rapidly growing NTM should be risk-stratified separately from slow-growing NTM, said Burnell. “Early growth of rapid-growing NTM should prompt careful evaluation and assessment in a multidisciplinary fashion and not be deemed colonization without thorough evaluation,” she said. Routine posttransplant cultures also may have prognostic value in graft failure, she noted.

However, additional research with more granular detail regarding patient characteristics would be useful for risk stratification, said Burnell. “For example, information about pretransplant colonization, type of transplant (single vs double), immunosuppressive regimens, co-infections, and other factors would be useful,” she said. The current study did not address delineation between colonization, transient isolation, and infection, and data on treatment regimens and timing were lacking; therefore, collaborative studies are needed to assess these factors and their relationship to patient outcomes, Burnell noted.

The study was funded by institutional grants from the National Heart, Lung, and Blood Institute. Mezochow and Burnell had no financial conflicts to disclose.

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

Rapid-growing nontuberculous mycobacteria (NTM) were strongly associated with death or retransplantation in adult lung transplant patients, based on data from a new study of about 1000 individuals.

NTM are ubiquitous environmental organisms, but the clinical significance of isolating NTM posttransplant remains poorly defined, and previous studies have been mainly small and single center, said lead author Gabrielle Mezochow, MD, a pulmonology and critical care fellow at the University of Pennsylvania in Philadelphia.

“This is important because treatment is particularly challenging in lung transplant recipients, requiring prolonged multidrug regimens that can be toxic and interact with immunosuppression,” Mezochow said. “We conducted this study to better understand how often NTM is isolated after lung transplant, and whether isolation is associated with important outcomes such as chronic lung allograft dysfunction (CLAD) and death or retransplantation in a large multicenter cohort,” she said.

In the study, presented at the annual meeting of the International Society for Heart and Lung Transplantation (ISHLT), Mezochow et al reviewed data from 1044 adult lung transplant recipients in the Lung Transplant Outcomes Group cohort who underwent transplant between 2007 and 2022 at 3 centers.

The researchers evaluated the time from transplantation to graft failure (defined as death or retransplantation) and CLAD (as defined by the ISHLT). They used a proportional hazards model adjusted for age, diagnosis, BMI, primary graft dysfunction, postoperative extracorporeal membrane oxygenation, and transplant type.

A total of 136 patients (13%) had pulmonary growth of NTM within a year of their transplants; the most common types were Mycobacterium avium (88 patients) and Mycobacterium abscessus (16 patients).

Overall, the association between early growth of any NTM and the risk for graft failure did not reach statistical significance (adjusted hazard ratio [HR], 1.27). However, patients who had early growth of rapid-growing NTM (including M abscessus, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium immunogenum, Mycobacterium mageritense, and Mycobacterium mucogenicum) had an increased risk for graft failure compared to those with early growth of slow-growing NTM such as M avium (unadjusted HR, 2.36; adjusted HR, 2.49). The associations were consistent when patients with cystic fibrosis were excluded, and no significant association was observed between early NTM growth by slow or rapid types and increased risk for CLAD (adjusted HR, 1.09).

“One of the most interesting findings was that associations differed by NTM species,” Mezochow said. “Rapid-growing NTM were most strongly associated with death or retransplantation, whereas slow-growing NTM appeared to have a stronger association with CLAD,” she said. “We were also intrigued by the stronger associations with negative outcomes observed among recipients with ILD [interstitial lung disease], particularly those undergoing single lung transplantation,” Mezochow noted. “This raises the possibility that characteristics of the native lung or underlying lung disease may influence susceptibility and outcomes,” she said.

“Importantly, our study evaluated NTM isolation rather than NTM pulmonary disease, which is often difficult to define in lung transplant recipients,” said Mezochow. The results suggest that NTM isolation should not be dismissed as a benign microbiologic finding and could serve as an early marker of lung transplant recipients at increased risk for poor outcomes, even before disease can be definitively established, she noted. “Certain subgroups of recipients, including those with specific NTM species or underlying diagnoses, may be at a particularly elevated risk for poor outcomes, while not all patients with NTM isolation are likely to require treatment,” she added.

Limitations and Next Steps

The findings were limited by several factors including the observational design and lack of detailed patient-level medication data including longitudinal immunosuppression, antibiotic exposures, and azithromycin use for bronchiolitis obliterans syndrome prevention, any of which could influence both NTM isolation and downstream outcomes, Mezochow said.

The researchers also were unable to adjudicate NTM pulmonary disease according to current guideline-based definitions because of the lack of longitudinal radiographic and symptom data, she added. “That said, these diagnostic criteria were developed outside the transplant setting and have not been validated in lung transplant recipients, so their applicability here is uncertain,” she added. “Although we focused on the first posttransplant year, when surveillance bronchoscopy is relatively routine, some residual ascertainment bias is still likely,” she noted.

“Future research should focus on identifying which recipients with NTM isolation are most likely to progress to CLAD or death, understanding the biologic mechanisms linking NTM and allograft injury, and determining whether treatment strategies or immunosuppression modifications can improve outcomes,” said Mezochow. “Ultimately, the goal is to develop a framework that helps clinicians distinguish who may benefit from treatment from those who can be safely observed,” she said.

Added Value for Patient Assessment

The current study addresses major questions in lung transplantation, namely, whether isolation of NTM species in the first year after a lung transplant is a marker of airway vulnerability, structural airway defects, patient frailty, or a true contributor to allograft function and failure, said Jacqueline Burnell, MD, an associate professor of clinical medicine at the Lewis Katz School of Medicine at Temple University in Philadelphia, and a specialist in infections in transplant and immunocompromised patients. “This study separated rapidly growing NTM from slow growers to attempt to identify species associated with poor outcomes and provide prognostication,” said Burnell, who was not involved in the study. The association of rapidly growing NTM and poorer outcomes was not surprising, she noted. “Mycobacterium abscessus species, which accounted for the majority of rapidly growing isolates, are thought to be more aggressive and are certainly more challenging to treat,” she said. “The absence of association with CLAD is interesting, as this has been found in other studies looking at NTM infections post-lung transplant,” she added.

The results suggest that rapidly growing NTM should be risk-stratified separately from slow-growing NTM, said Burnell. “Early growth of rapid-growing NTM should prompt careful evaluation and assessment in a multidisciplinary fashion and not be deemed colonization without thorough evaluation,” she said. Routine posttransplant cultures also may have prognostic value in graft failure, she noted.

However, additional research with more granular detail regarding patient characteristics would be useful for risk stratification, said Burnell. “For example, information about pretransplant colonization, type of transplant (single vs double), immunosuppressive regimens, co-infections, and other factors would be useful,” she said. The current study did not address delineation between colonization, transient isolation, and infection, and data on treatment regimens and timing were lacking; therefore, collaborative studies are needed to assess these factors and their relationship to patient outcomes, Burnell noted.

The study was funded by institutional grants from the National Heart, Lung, and Blood Institute. Mezochow and Burnell had no financial conflicts to disclose.

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

Rapid-growing nontuberculous mycobacteria (NTM) were strongly associated with death or retransplantation in adult lung transplant patients, based on data from a new study of about 1000 individuals.

NTM are ubiquitous environmental organisms, but the clinical significance of isolating NTM posttransplant remains poorly defined, and previous studies have been mainly small and single center, said lead author Gabrielle Mezochow, MD, a pulmonology and critical care fellow at the University of Pennsylvania in Philadelphia.

“This is important because treatment is particularly challenging in lung transplant recipients, requiring prolonged multidrug regimens that can be toxic and interact with immunosuppression,” Mezochow said. “We conducted this study to better understand how often NTM is isolated after lung transplant, and whether isolation is associated with important outcomes such as chronic lung allograft dysfunction (CLAD) and death or retransplantation in a large multicenter cohort,” she said.

In the study, presented at the annual meeting of the International Society for Heart and Lung Transplantation (ISHLT), Mezochow et al reviewed data from 1044 adult lung transplant recipients in the Lung Transplant Outcomes Group cohort who underwent transplant between 2007 and 2022 at 3 centers.

The researchers evaluated the time from transplantation to graft failure (defined as death or retransplantation) and CLAD (as defined by the ISHLT). They used a proportional hazards model adjusted for age, diagnosis, BMI, primary graft dysfunction, postoperative extracorporeal membrane oxygenation, and transplant type.

A total of 136 patients (13%) had pulmonary growth of NTM within a year of their transplants; the most common types were Mycobacterium avium (88 patients) and Mycobacterium abscessus (16 patients).

Overall, the association between early growth of any NTM and the risk for graft failure did not reach statistical significance (adjusted hazard ratio [HR], 1.27). However, patients who had early growth of rapid-growing NTM (including M abscessus, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium immunogenum, Mycobacterium mageritense, and Mycobacterium mucogenicum) had an increased risk for graft failure compared to those with early growth of slow-growing NTM such as M avium (unadjusted HR, 2.36; adjusted HR, 2.49). The associations were consistent when patients with cystic fibrosis were excluded, and no significant association was observed between early NTM growth by slow or rapid types and increased risk for CLAD (adjusted HR, 1.09).

“One of the most interesting findings was that associations differed by NTM species,” Mezochow said. “Rapid-growing NTM were most strongly associated with death or retransplantation, whereas slow-growing NTM appeared to have a stronger association with CLAD,” she said. “We were also intrigued by the stronger associations with negative outcomes observed among recipients with ILD [interstitial lung disease], particularly those undergoing single lung transplantation,” Mezochow noted. “This raises the possibility that characteristics of the native lung or underlying lung disease may influence susceptibility and outcomes,” she said.

“Importantly, our study evaluated NTM isolation rather than NTM pulmonary disease, which is often difficult to define in lung transplant recipients,” said Mezochow. The results suggest that NTM isolation should not be dismissed as a benign microbiologic finding and could serve as an early marker of lung transplant recipients at increased risk for poor outcomes, even before disease can be definitively established, she noted. “Certain subgroups of recipients, including those with specific NTM species or underlying diagnoses, may be at a particularly elevated risk for poor outcomes, while not all patients with NTM isolation are likely to require treatment,” she added.

Limitations and Next Steps

The findings were limited by several factors including the observational design and lack of detailed patient-level medication data including longitudinal immunosuppression, antibiotic exposures, and azithromycin use for bronchiolitis obliterans syndrome prevention, any of which could influence both NTM isolation and downstream outcomes, Mezochow said.

The researchers also were unable to adjudicate NTM pulmonary disease according to current guideline-based definitions because of the lack of longitudinal radiographic and symptom data, she added. “That said, these diagnostic criteria were developed outside the transplant setting and have not been validated in lung transplant recipients, so their applicability here is uncertain,” she added. “Although we focused on the first posttransplant year, when surveillance bronchoscopy is relatively routine, some residual ascertainment bias is still likely,” she noted.

“Future research should focus on identifying which recipients with NTM isolation are most likely to progress to CLAD or death, understanding the biologic mechanisms linking NTM and allograft injury, and determining whether treatment strategies or immunosuppression modifications can improve outcomes,” said Mezochow. “Ultimately, the goal is to develop a framework that helps clinicians distinguish who may benefit from treatment from those who can be safely observed,” she said.

Added Value for Patient Assessment

The current study addresses major questions in lung transplantation, namely, whether isolation of NTM species in the first year after a lung transplant is a marker of airway vulnerability, structural airway defects, patient frailty, or a true contributor to allograft function and failure, said Jacqueline Burnell, MD, an associate professor of clinical medicine at the Lewis Katz School of Medicine at Temple University in Philadelphia, and a specialist in infections in transplant and immunocompromised patients. “This study separated rapidly growing NTM from slow growers to attempt to identify species associated with poor outcomes and provide prognostication,” said Burnell, who was not involved in the study. The association of rapidly growing NTM and poorer outcomes was not surprising, she noted. “Mycobacterium abscessus species, which accounted for the majority of rapidly growing isolates, are thought to be more aggressive and are certainly more challenging to treat,” she said. “The absence of association with CLAD is interesting, as this has been found in other studies looking at NTM infections post-lung transplant,” she added.

The results suggest that rapidly growing NTM should be risk-stratified separately from slow-growing NTM, said Burnell. “Early growth of rapid-growing NTM should prompt careful evaluation and assessment in a multidisciplinary fashion and not be deemed colonization without thorough evaluation,” she said. Routine posttransplant cultures also may have prognostic value in graft failure, she noted.

However, additional research with more granular detail regarding patient characteristics would be useful for risk stratification, said Burnell. “For example, information about pretransplant colonization, type of transplant (single vs double), immunosuppressive regimens, co-infections, and other factors would be useful,” she said. The current study did not address delineation between colonization, transient isolation, and infection, and data on treatment regimens and timing were lacking; therefore, collaborative studies are needed to assess these factors and their relationship to patient outcomes, Burnell noted.

The study was funded by institutional grants from the National Heart, Lung, and Blood Institute. Mezochow and Burnell had no financial conflicts to disclose.

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

June 24 (Reuters) - The US military has resumed requiring flu vaccines for some service members in an exception to Defense Secretary Pete Hegseth’s guidance declaring the shots voluntary 2 months ago.

The decision follows a flu outbreak among recruits at Joint Base San Antonio-Lackland in Texas and sharp criticism of the policy from public health experts. More than 220 ‌recruits have been diagnosed with influenza and 4 hospitalized in the outbreak, according to media reports.

Hegseth said in April that the annual flu vaccine would become optional for all US military personnel under the Pentagon’s new vaccine policy. It ‌had previously been mandated and considered critical to troop preparedness.

The Under Secretary for War ‌Personnel and Readiness approved exception requests ‌for the Army, Navy, Air Force, National Security Agency, and Defense Health Agency, according to a statement from chief Pentagon spokesperson Sean Parnell on ‌Wednesday.

“The decisions were based upon thorough risk assessments and are designed to maximize operational readiness, lethality, ‌and force generation, while safeguarding at-risk populations,” Parnell said.

Each department is responsible for implementation, the spokesperson added.

The World Health Organization recommends the flu shot for those aged ≥ 6 months.

Trump administration Health Secretary Robert ‌F. ‌Kennedy Jr., a longtime antivaccine activist, has enacted policies that have decreased the use ‌of inoculations in the US, including dropping its 2025 flu vaccine campaign. Kennedy’s Make America Healthy Again movement has sought to weaken school enrollment mandates around the country.

Flu vaccines from Sanofi, CSL Seqirus, GSK and AstraZeneca are approved ‌in the United States.

(Reporting by Idrees Ali, Mariam Sunny and Mrinalika Roy; Editing by Caroline Humer and Bill Berkrot)

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

June 24 (Reuters) - The US military has resumed requiring flu vaccines for some service members in an exception to Defense Secretary Pete Hegseth’s guidance declaring the shots voluntary 2 months ago.

The decision follows a flu outbreak among recruits at Joint Base San Antonio-Lackland in Texas and sharp criticism of the policy from public health experts. More than 220 ‌recruits have been diagnosed with influenza and 4 hospitalized in the outbreak, according to media reports.

Hegseth said in April that the annual flu vaccine would become optional for all US military personnel under the Pentagon’s new vaccine policy. It ‌had previously been mandated and considered critical to troop preparedness.

The Under Secretary for War ‌Personnel and Readiness approved exception requests ‌for the Army, Navy, Air Force, National Security Agency, and Defense Health Agency, according to a statement from chief Pentagon spokesperson Sean Parnell on ‌Wednesday.

“The decisions were based upon thorough risk assessments and are designed to maximize operational readiness, lethality, ‌and force generation, while safeguarding at-risk populations,” Parnell said.

Each department is responsible for implementation, the spokesperson added.

The World Health Organization recommends the flu shot for those aged ≥ 6 months.

Trump administration Health Secretary Robert ‌F. ‌Kennedy Jr., a longtime antivaccine activist, has enacted policies that have decreased the use ‌of inoculations in the US, including dropping its 2025 flu vaccine campaign. Kennedy’s Make America Healthy Again movement has sought to weaken school enrollment mandates around the country.

Flu vaccines from Sanofi, CSL Seqirus, GSK and AstraZeneca are approved ‌in the United States.

(Reporting by Idrees Ali, Mariam Sunny and Mrinalika Roy; Editing by Caroline Humer and Bill Berkrot)

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

June 24 (Reuters) - The US military has resumed requiring flu vaccines for some service members in an exception to Defense Secretary Pete Hegseth’s guidance declaring the shots voluntary 2 months ago.

The decision follows a flu outbreak among recruits at Joint Base San Antonio-Lackland in Texas and sharp criticism of the policy from public health experts. More than 220 ‌recruits have been diagnosed with influenza and 4 hospitalized in the outbreak, according to media reports.

Hegseth said in April that the annual flu vaccine would become optional for all US military personnel under the Pentagon’s new vaccine policy. It ‌had previously been mandated and considered critical to troop preparedness.

The Under Secretary for War ‌Personnel and Readiness approved exception requests ‌for the Army, Navy, Air Force, National Security Agency, and Defense Health Agency, according to a statement from chief Pentagon spokesperson Sean Parnell on ‌Wednesday.

“The decisions were based upon thorough risk assessments and are designed to maximize operational readiness, lethality, ‌and force generation, while safeguarding at-risk populations,” Parnell said.

Each department is responsible for implementation, the spokesperson added.

The World Health Organization recommends the flu shot for those aged ≥ 6 months.

Trump administration Health Secretary Robert ‌F. ‌Kennedy Jr., a longtime antivaccine activist, has enacted policies that have decreased the use ‌of inoculations in the US, including dropping its 2025 flu vaccine campaign. Kennedy’s Make America Healthy Again movement has sought to weaken school enrollment mandates around the country.

Flu vaccines from Sanofi, CSL Seqirus, GSK and AstraZeneca are approved ‌in the United States.

(Reporting by Idrees Ali, Mariam Sunny and Mrinalika Roy; Editing by Caroline Humer and Bill Berkrot)

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

A retrospective cohort study links clomiphene citrate (CC) to significantly lower mortality rates when compared with testosterone replacement therapy (TRT) in male veterans with hypogonadism or infertility. CC is not approved by the US Food and Drug Administration (FDA) for hypogonadism but is often used off label. Patients taking clomiphene also had significantly lower risk of diseases of the circulatory system, brain, and bones. 

The study tracked matched cohorts of 2518 patients taking CC or TRT for a mean 3.5 years. All-cause mortality was lower in the CC group (1.83%) than the TRT group (10.13%, P < .001), reported researchers at the Kansas City Veterans Affairs Medical Center and University of Missouri-Kansas City School of Medicine, et al in Andrology.

The researchers also reported that outcomes were better in the CC group than the TRT group for new-onset hypertension (6.04% vs 10.48%, P < .001), cerebrovascular accident (0.52% vs 1.43%, P < .001), coronary artery disease (1.51% vs 2.26%, P < .048), polycythemia (1.07% vs 2.22%, P < .001), and osteoporosis (1.15% vs 2.07%, P = .009), respectively. 

“It seems like clomiphene is a good medication to be used long term, but we still need more investigation into this,” endocrinologist Mariana Garcia-Touza, MD said in an interview with Federal Practitioner. 

TRT is a common therapy for male hypogonadism, although the study notes it is linked to thickened blood, breast growth, infertility, fluid retention, obstructive sleep apnea, and cardiovascular and prostate problems. Guidelines recommend against its use in patients with prostate cancer, at high cardiovascular risk, and those trying to have children.

CC is a selective estrogen receptor modulator and used off-label to treat male hypogonadism because it can boost the production of testosterone. The study notes how many Veterans health Administration patients have low testosterone, with previous research reporting the rate among veterans aged ≥ 60 years at 34%. 

Garcia-Touza was especially interested in any effect clomiphene has on bones: “We’ve been hearing that it probably affects the bone and can cause osteoporosis, but no one has looked into it.”

The study tracked veterans from December 1990 to September 2024; follow-ups lasted up to 34 years. Patient mean ages were 46.5 and 47.5 years for the HRT and CC groups, respectively. Hypogonadism was the treatment indication for 98.4% and 64.5% and infertility was the indication for 1.6% and 35.5% for the HRT and CC groups, respectively. About 70% of both groups were White. 

There were no statistically significant gaps between the groups regarding hip fractures, pulmonary embolism, thrombosis, and vertebral fractures. Garcia-Touza said the all-cause mortality gap the study reported was surprising, although the study did not control for factors that may have differed between the groups.

“This needs to be more carefully examined to see if this is a real finding or if there is some bias in the study that is causing it,” she said.

Moving forward, Garcia-Touza said she hopes to launch a prospective study of TRT vs CC.

Parviz K. Kavoussi, MD, a reproductive urologist at the University of Texas at Austin who was not involved in the study, said in an interview the study’s findings highlight the importance of monitoring patients on TRT for an increase in hematocrit. 

“Not all testosterone replacement therapies are created equal from this standpoint,” he said, noting that risk depends on the delivery method. “There are multiple modalities — topical gels, patches, nasal gels, intramuscular injections, subcutaneous pellets, subcutaneous autoinjector pens, and oral testosterone pills. Each of these has a defined percentage risk of secondary erythrocytosis, with some being significantly higher than others.”

As for other potential risks from TRT such as a possible higher mortality rate, Kavoussi noted that a landmark 2023 trial of middle-aged and older men convinced the FDA to no longer require testosterone products to include a black-box warning about cardiovascular disease. 

Regarding the question of whether clomiphene works as well as testosterone, Kavoussi noted his group’s research has found clomiphene can normalize testosterone levels biochemically. However, “where clomiphene typically falls short in data and in clinical practice is the level of symptomatic improvement in testosterone deficiency symptoms that patients can achieve in comparison to exogenous testosterone replacement.” 

No funding was reported, and the authors – including Garcia-Touza – had no disclosures. Kavoussi discloses relationships with Halozyme and Verity.

A retrospective cohort study links clomiphene citrate (CC) to significantly lower mortality rates when compared with testosterone replacement therapy (TRT) in male veterans with hypogonadism or infertility. CC is not approved by the US Food and Drug Administration (FDA) for hypogonadism but is often used off label. Patients taking clomiphene also had significantly lower risk of diseases of the circulatory system, brain, and bones. 

The study tracked matched cohorts of 2518 patients taking CC or TRT for a mean 3.5 years. All-cause mortality was lower in the CC group (1.83%) than the TRT group (10.13%, P < .001), reported researchers at the Kansas City Veterans Affairs Medical Center and University of Missouri-Kansas City School of Medicine, et al in Andrology.

The researchers also reported that outcomes were better in the CC group than the TRT group for new-onset hypertension (6.04% vs 10.48%, P < .001), cerebrovascular accident (0.52% vs 1.43%, P < .001), coronary artery disease (1.51% vs 2.26%, P < .048), polycythemia (1.07% vs 2.22%, P < .001), and osteoporosis (1.15% vs 2.07%, P = .009), respectively. 

“It seems like clomiphene is a good medication to be used long term, but we still need more investigation into this,” endocrinologist Mariana Garcia-Touza, MD said in an interview with Federal Practitioner. 

TRT is a common therapy for male hypogonadism, although the study notes it is linked to thickened blood, breast growth, infertility, fluid retention, obstructive sleep apnea, and cardiovascular and prostate problems. Guidelines recommend against its use in patients with prostate cancer, at high cardiovascular risk, and those trying to have children.

CC is a selective estrogen receptor modulator and used off-label to treat male hypogonadism because it can boost the production of testosterone. The study notes how many Veterans health Administration patients have low testosterone, with previous research reporting the rate among veterans aged ≥ 60 years at 34%. 

Garcia-Touza was especially interested in any effect clomiphene has on bones: “We’ve been hearing that it probably affects the bone and can cause osteoporosis, but no one has looked into it.”

The study tracked veterans from December 1990 to September 2024; follow-ups lasted up to 34 years. Patient mean ages were 46.5 and 47.5 years for the HRT and CC groups, respectively. Hypogonadism was the treatment indication for 98.4% and 64.5% and infertility was the indication for 1.6% and 35.5% for the HRT and CC groups, respectively. About 70% of both groups were White. 

There were no statistically significant gaps between the groups regarding hip fractures, pulmonary embolism, thrombosis, and vertebral fractures. Garcia-Touza said the all-cause mortality gap the study reported was surprising, although the study did not control for factors that may have differed between the groups.

“This needs to be more carefully examined to see if this is a real finding or if there is some bias in the study that is causing it,” she said.

Moving forward, Garcia-Touza said she hopes to launch a prospective study of TRT vs CC.

Parviz K. Kavoussi, MD, a reproductive urologist at the University of Texas at Austin who was not involved in the study, said in an interview the study’s findings highlight the importance of monitoring patients on TRT for an increase in hematocrit. 

“Not all testosterone replacement therapies are created equal from this standpoint,” he said, noting that risk depends on the delivery method. “There are multiple modalities — topical gels, patches, nasal gels, intramuscular injections, subcutaneous pellets, subcutaneous autoinjector pens, and oral testosterone pills. Each of these has a defined percentage risk of secondary erythrocytosis, with some being significantly higher than others.”

As for other potential risks from TRT such as a possible higher mortality rate, Kavoussi noted that a landmark 2023 trial of middle-aged and older men convinced the FDA to no longer require testosterone products to include a black-box warning about cardiovascular disease. 

Regarding the question of whether clomiphene works as well as testosterone, Kavoussi noted his group’s research has found clomiphene can normalize testosterone levels biochemically. However, “where clomiphene typically falls short in data and in clinical practice is the level of symptomatic improvement in testosterone deficiency symptoms that patients can achieve in comparison to exogenous testosterone replacement.” 

No funding was reported, and the authors – including Garcia-Touza – had no disclosures. Kavoussi discloses relationships with Halozyme and Verity.

A retrospective cohort study links clomiphene citrate (CC) to significantly lower mortality rates when compared with testosterone replacement therapy (TRT) in male veterans with hypogonadism or infertility. CC is not approved by the US Food and Drug Administration (FDA) for hypogonadism but is often used off label. Patients taking clomiphene also had significantly lower risk of diseases of the circulatory system, brain, and bones. 

The study tracked matched cohorts of 2518 patients taking CC or TRT for a mean 3.5 years. All-cause mortality was lower in the CC group (1.83%) than the TRT group (10.13%, P < .001), reported researchers at the Kansas City Veterans Affairs Medical Center and University of Missouri-Kansas City School of Medicine, et al in Andrology.

The researchers also reported that outcomes were better in the CC group than the TRT group for new-onset hypertension (6.04% vs 10.48%, P < .001), cerebrovascular accident (0.52% vs 1.43%, P < .001), coronary artery disease (1.51% vs 2.26%, P < .048), polycythemia (1.07% vs 2.22%, P < .001), and osteoporosis (1.15% vs 2.07%, P = .009), respectively. 

“It seems like clomiphene is a good medication to be used long term, but we still need more investigation into this,” endocrinologist Mariana Garcia-Touza, MD said in an interview with Federal Practitioner. 

TRT is a common therapy for male hypogonadism, although the study notes it is linked to thickened blood, breast growth, infertility, fluid retention, obstructive sleep apnea, and cardiovascular and prostate problems. Guidelines recommend against its use in patients with prostate cancer, at high cardiovascular risk, and those trying to have children.

CC is a selective estrogen receptor modulator and used off-label to treat male hypogonadism because it can boost the production of testosterone. The study notes how many Veterans health Administration patients have low testosterone, with previous research reporting the rate among veterans aged ≥ 60 years at 34%. 

Garcia-Touza was especially interested in any effect clomiphene has on bones: “We’ve been hearing that it probably affects the bone and can cause osteoporosis, but no one has looked into it.”

The study tracked veterans from December 1990 to September 2024; follow-ups lasted up to 34 years. Patient mean ages were 46.5 and 47.5 years for the HRT and CC groups, respectively. Hypogonadism was the treatment indication for 98.4% and 64.5% and infertility was the indication for 1.6% and 35.5% for the HRT and CC groups, respectively. About 70% of both groups were White. 

There were no statistically significant gaps between the groups regarding hip fractures, pulmonary embolism, thrombosis, and vertebral fractures. Garcia-Touza said the all-cause mortality gap the study reported was surprising, although the study did not control for factors that may have differed between the groups.

“This needs to be more carefully examined to see if this is a real finding or if there is some bias in the study that is causing it,” she said.

Moving forward, Garcia-Touza said she hopes to launch a prospective study of TRT vs CC.

Parviz K. Kavoussi, MD, a reproductive urologist at the University of Texas at Austin who was not involved in the study, said in an interview the study’s findings highlight the importance of monitoring patients on TRT for an increase in hematocrit. 

“Not all testosterone replacement therapies are created equal from this standpoint,” he said, noting that risk depends on the delivery method. “There are multiple modalities — topical gels, patches, nasal gels, intramuscular injections, subcutaneous pellets, subcutaneous autoinjector pens, and oral testosterone pills. Each of these has a defined percentage risk of secondary erythrocytosis, with some being significantly higher than others.”

As for other potential risks from TRT such as a possible higher mortality rate, Kavoussi noted that a landmark 2023 trial of middle-aged and older men convinced the FDA to no longer require testosterone products to include a black-box warning about cardiovascular disease. 

Regarding the question of whether clomiphene works as well as testosterone, Kavoussi noted his group’s research has found clomiphene can normalize testosterone levels biochemically. However, “where clomiphene typically falls short in data and in clinical practice is the level of symptomatic improvement in testosterone deficiency symptoms that patients can achieve in comparison to exogenous testosterone replacement.” 

No funding was reported, and the authors – including Garcia-Touza – had no disclosures. Kavoussi discloses relationships with Halozyme and Verity.

The heart is one of the organs least likely to develop cancer, a long-standing biologic puzzle that may now have an explanation. A study published in Science found that the mechanical load generated by the beating heart suppresses tumor cell proliferation through a molecular pathway that alters gene expression, raising the possibility of new therapeutic targets.

Mechanical Protection

Tumors that originate directly in the myocardium are exceptionally rare, occurring in < 1% of autopsies. Even cardiac metastases, which have been reported in up to 18% of autopsies, are often small, asymptomatic, and incidentally discovered. Although this phenomenon has long been recognized, its biologic basis remains unclear.

The heart is notable for its limited capacity for regeneration. After birth, cardiomyocytes stop dividing and subsequently renew at a rate of about 1% per year. However, when the mechanical load is reduced, such as in patients supported by left ventricular assist devices, cardiomyocytes once again show signs of proliferation.

This observation prompted researchers to investigate whether the same mechanical load that restrains normal cardiac cells might also suppress cancer growth.

More Load, Less Growth

To investigate this question, researchers introduced two genetic alterations commonly found in human cancers, activation of the KRAS oncogene and loss of the TP53, into the liver, skeletal muscle, and hearts of mice. Tumors developed in multiple organs, but not in the heart.

The researchers then used a heterotopic heart transplant model in which a donor mouse’s heart is surgically connected to the neck (cervical) or abdominal vessels of a recipient mouse. The transplanted heart remained perfused but lost its normal mechanical loading (constant beating).

When researchers injected lung adenocarcinoma cells into 2 different hearts of the same animal, they observed entirely different outcomes. The cancer cells did not grow in the native mechanically loaded heart. However, the same cells grew rapidly and extensively in the mechanically unloaded transplanted heart.

Tumor cells had replaced nearly all normal tissue in the unloaded heart, whereas they occupied only approximately 20% of the ventricle in the native heart in 14 days. This difference could not be explained by differences in the initial tumor engraftment or cell death. Instead, the findings pointed to substantial differences in tumor cell proliferation.

Similar results were observed in bioengineered cardiac tissues exposed to varying degrees of mechanical stress. Tumor cells proliferated under conditions of low mechanical load but ceased proliferating as the mechanical load increased. Tumor growth was lowest in regions exposed to the greatest mechanical stimulation of cardiomyocytes in vitro.

However, the possibility of metabolic competition between cardiac and tumor cells for nutrition was ruled out.

From Mechanics to Genes

Next, we examined the influence of mechanical forces on tumor cell behavior.

Gene expression analyses of both human cardiac metastases and mouse tumor cells showed that mechanical stimulation altered chromatin accessibility through the activation of genes involved in chromatin remodeling. These changes promoted the expression of genes that suppress cell division.

The study also identified Nesprin-2, a part of the linker of the nucleoskeleton and cytoskeleton complex, which acts as a physical bridge. It is a multitasking protein that connects the cell’s outer structural network (cytoskeleton) to its inner genetic storage (nucleus) and appears to play a significant role in converting mechanical signals into changes in gene expression.

When Nesprin-2 was inactivated, cancer cells resumed proliferation despite exposure to a mechanical load, both in engineered tissues and animal models.

“Collectively, these results shed light on the role of mechanical forces in protecting the heart from cancer and may pave the way to cancer therapies based on mechanical stimulation,” concluded the authors.

An Actively Protected Organ

Speaking with Univadis Italy, part of the Medscape Professional Network, Giorgio Scita, PhD, director of the Mechanisms of Tumor Cell Migration research unit at AIRC Institute of Molecular Oncology and professor of general pathology at the University of Milan in Milan, Italy, said, “The study addressed a simple but fundamental question: Why is the heart largely resistant to cancer despite being highly vascularized and continuously exposed to circulating tumor cells?

These findings suggest that the heartbeat itself creates a mechanical environment that is hostile to tumor growth. The compressive forces generated by rhythmic myocardial contraction are sensed by cancer cells and translated into biochemical signals that limit their proliferation.

In this view, the heart is not simply an organ that is unfavorable for cancer growth but a tissue actively protected by its own mechanical forces.”

Speaking with Univadis Italy, Serena Zacchigna, PhD, study coauthor and head of the Cardiovascular Biology Laboratory at the International Centre for Genetic Engineering and Biotechnology, Trieste, Italy, said, “Until now, however, attention had focused primarily on signals from the extracellular matrix, such as tissue stiffness. Our study adds a new element: even forces generated directly by the movement of an organ — in this case, cardiac contraction — can influence the growth of cancer cells.”

Beyond the Heart

Scita said the findings have implications that extend well beyond the heart.

“The most significant aspect is that this work identifies tissue mechanics as an active regulator of tumor behavior,” he said. Stiffness, compression, tension, and confinement are not merely consequences of tumor growth, but factors capable of influencing proliferation, invasion, and dormancy.

The concept may apply to many solid tumors. Scita noted that cancer cells growing in confined environments, such as ductal carcinoma in situ of the breast, are exposed to substantial mechanical constraints. Understanding why some tumor cells remain susceptible to these forces whereas others evade them and become invasive remains a major unanswered question in cancer biology.

Research on these mechanisms is expanding internationally and in Italy as well. One example is the AIRC “5 per mille” (5 per thousand) research programs on metastatic disease, which includes projects designed to clarify how the mechanical properties of tumor tissue influence cancer initiation, metastatic spread, and disease progression.

Therapeutic Potential

According to Zacchigna, these findings open 2 principal avenues for future research.

“The first focuses on mechanical stimulation itself. In collaboration with engineers at the University of Siena, including a group led by Domenico Prattichizzo, researchers are developing wearable robotic devices designed to mimic the heartbeat and deliver mechanical stimulation to superficial solid tumors such as certain skin cancers.

The second approach is pharmacology. Researchers are investigating whether epigenetic therapies capable of modifying chromatin remodeling can reproduce the effects of cardiac contraction and suppress tumor cell proliferation.

However, Zacchigna cautioned that this work remains at an early experimental phase.”

However, before therapeutic applications can be pursued, important mechanistic questions remain unanswered.

Zacchigna noted that although the linker of nucleoskeleton and cytoskeleton (LINC) complex and Nesprin-2 are involved in signal transduction leading to chromatin reorganization and activation of cell cycle inhibitory loci, the molecular intermediates involved have yet to be fully defined.

Researchers also need to determine which genes are most critical, whether the mechanism operates across different tumor types, and whether it can be safely manipulated for therapeutic purposes.

In an accompanying commentary published in Science, Wyatt G. Paltzer, PhD, and James F. Martin, MD, from the Department of Integrative Physiology at the Baylor College of Medicine in Houston, noted that the findings suggest enhancing LINC complex activity could potentially suppress tumor growth.

However, because the complex has broad biologic functions, it may prove difficult to target therapeutically. The authors suggested that future studies should focus on identifying proteins that interact with Nesprin-2 or other components of the LINC complex and play a more specific role in inhibiting cancer cell proliferation.

Looking Ahead

Despite these challenges, Scita said that the study’s conceptual significance is already clear.

“Even if therapeutic applications remain years away, the findings suggest that cancer may one day be targeted by altering how tumor cells perceive and interpret physical forces.”

Scita and Zacchigna reported having no relevant conflicts of interest.

This story was translated from Univadis Italy.

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

The heart is one of the organs least likely to develop cancer, a long-standing biologic puzzle that may now have an explanation. A study published in Science found that the mechanical load generated by the beating heart suppresses tumor cell proliferation through a molecular pathway that alters gene expression, raising the possibility of new therapeutic targets.

Mechanical Protection

Tumors that originate directly in the myocardium are exceptionally rare, occurring in < 1% of autopsies. Even cardiac metastases, which have been reported in up to 18% of autopsies, are often small, asymptomatic, and incidentally discovered. Although this phenomenon has long been recognized, its biologic basis remains unclear.

The heart is notable for its limited capacity for regeneration. After birth, cardiomyocytes stop dividing and subsequently renew at a rate of about 1% per year. However, when the mechanical load is reduced, such as in patients supported by left ventricular assist devices, cardiomyocytes once again show signs of proliferation.

This observation prompted researchers to investigate whether the same mechanical load that restrains normal cardiac cells might also suppress cancer growth.

More Load, Less Growth

To investigate this question, researchers introduced two genetic alterations commonly found in human cancers, activation of the KRAS oncogene and loss of the TP53, into the liver, skeletal muscle, and hearts of mice. Tumors developed in multiple organs, but not in the heart.

The researchers then used a heterotopic heart transplant model in which a donor mouse’s heart is surgically connected to the neck (cervical) or abdominal vessels of a recipient mouse. The transplanted heart remained perfused but lost its normal mechanical loading (constant beating).

When researchers injected lung adenocarcinoma cells into 2 different hearts of the same animal, they observed entirely different outcomes. The cancer cells did not grow in the native mechanically loaded heart. However, the same cells grew rapidly and extensively in the mechanically unloaded transplanted heart.

Tumor cells had replaced nearly all normal tissue in the unloaded heart, whereas they occupied only approximately 20% of the ventricle in the native heart in 14 days. This difference could not be explained by differences in the initial tumor engraftment or cell death. Instead, the findings pointed to substantial differences in tumor cell proliferation.

Similar results were observed in bioengineered cardiac tissues exposed to varying degrees of mechanical stress. Tumor cells proliferated under conditions of low mechanical load but ceased proliferating as the mechanical load increased. Tumor growth was lowest in regions exposed to the greatest mechanical stimulation of cardiomyocytes in vitro.

However, the possibility of metabolic competition between cardiac and tumor cells for nutrition was ruled out.

From Mechanics to Genes

Next, we examined the influence of mechanical forces on tumor cell behavior.

Gene expression analyses of both human cardiac metastases and mouse tumor cells showed that mechanical stimulation altered chromatin accessibility through the activation of genes involved in chromatin remodeling. These changes promoted the expression of genes that suppress cell division.

The study also identified Nesprin-2, a part of the linker of the nucleoskeleton and cytoskeleton complex, which acts as a physical bridge. It is a multitasking protein that connects the cell’s outer structural network (cytoskeleton) to its inner genetic storage (nucleus) and appears to play a significant role in converting mechanical signals into changes in gene expression.

When Nesprin-2 was inactivated, cancer cells resumed proliferation despite exposure to a mechanical load, both in engineered tissues and animal models.

“Collectively, these results shed light on the role of mechanical forces in protecting the heart from cancer and may pave the way to cancer therapies based on mechanical stimulation,” concluded the authors.

An Actively Protected Organ

Speaking with Univadis Italy, part of the Medscape Professional Network, Giorgio Scita, PhD, director of the Mechanisms of Tumor Cell Migration research unit at AIRC Institute of Molecular Oncology and professor of general pathology at the University of Milan in Milan, Italy, said, “The study addressed a simple but fundamental question: Why is the heart largely resistant to cancer despite being highly vascularized and continuously exposed to circulating tumor cells?

These findings suggest that the heartbeat itself creates a mechanical environment that is hostile to tumor growth. The compressive forces generated by rhythmic myocardial contraction are sensed by cancer cells and translated into biochemical signals that limit their proliferation.

In this view, the heart is not simply an organ that is unfavorable for cancer growth but a tissue actively protected by its own mechanical forces.”

Speaking with Univadis Italy, Serena Zacchigna, PhD, study coauthor and head of the Cardiovascular Biology Laboratory at the International Centre for Genetic Engineering and Biotechnology, Trieste, Italy, said, “Until now, however, attention had focused primarily on signals from the extracellular matrix, such as tissue stiffness. Our study adds a new element: even forces generated directly by the movement of an organ — in this case, cardiac contraction — can influence the growth of cancer cells.”

Beyond the Heart

Scita said the findings have implications that extend well beyond the heart.

“The most significant aspect is that this work identifies tissue mechanics as an active regulator of tumor behavior,” he said. Stiffness, compression, tension, and confinement are not merely consequences of tumor growth, but factors capable of influencing proliferation, invasion, and dormancy.

The concept may apply to many solid tumors. Scita noted that cancer cells growing in confined environments, such as ductal carcinoma in situ of the breast, are exposed to substantial mechanical constraints. Understanding why some tumor cells remain susceptible to these forces whereas others evade them and become invasive remains a major unanswered question in cancer biology.

Research on these mechanisms is expanding internationally and in Italy as well. One example is the AIRC “5 per mille” (5 per thousand) research programs on metastatic disease, which includes projects designed to clarify how the mechanical properties of tumor tissue influence cancer initiation, metastatic spread, and disease progression.

Therapeutic Potential

According to Zacchigna, these findings open 2 principal avenues for future research.

“The first focuses on mechanical stimulation itself. In collaboration with engineers at the University of Siena, including a group led by Domenico Prattichizzo, researchers are developing wearable robotic devices designed to mimic the heartbeat and deliver mechanical stimulation to superficial solid tumors such as certain skin cancers.

The second approach is pharmacology. Researchers are investigating whether epigenetic therapies capable of modifying chromatin remodeling can reproduce the effects of cardiac contraction and suppress tumor cell proliferation.

However, Zacchigna cautioned that this work remains at an early experimental phase.”

However, before therapeutic applications can be pursued, important mechanistic questions remain unanswered.

Zacchigna noted that although the linker of nucleoskeleton and cytoskeleton (LINC) complex and Nesprin-2 are involved in signal transduction leading to chromatin reorganization and activation of cell cycle inhibitory loci, the molecular intermediates involved have yet to be fully defined.

Researchers also need to determine which genes are most critical, whether the mechanism operates across different tumor types, and whether it can be safely manipulated for therapeutic purposes.

In an accompanying commentary published in Science, Wyatt G. Paltzer, PhD, and James F. Martin, MD, from the Department of Integrative Physiology at the Baylor College of Medicine in Houston, noted that the findings suggest enhancing LINC complex activity could potentially suppress tumor growth.

However, because the complex has broad biologic functions, it may prove difficult to target therapeutically. The authors suggested that future studies should focus on identifying proteins that interact with Nesprin-2 or other components of the LINC complex and play a more specific role in inhibiting cancer cell proliferation.

Looking Ahead

Despite these challenges, Scita said that the study’s conceptual significance is already clear.

“Even if therapeutic applications remain years away, the findings suggest that cancer may one day be targeted by altering how tumor cells perceive and interpret physical forces.”

Scita and Zacchigna reported having no relevant conflicts of interest.

This story was translated from Univadis Italy.

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

The heart is one of the organs least likely to develop cancer, a long-standing biologic puzzle that may now have an explanation. A study published in Science found that the mechanical load generated by the beating heart suppresses tumor cell proliferation through a molecular pathway that alters gene expression, raising the possibility of new therapeutic targets.

Mechanical Protection

Tumors that originate directly in the myocardium are exceptionally rare, occurring in < 1% of autopsies. Even cardiac metastases, which have been reported in up to 18% of autopsies, are often small, asymptomatic, and incidentally discovered. Although this phenomenon has long been recognized, its biologic basis remains unclear.

The heart is notable for its limited capacity for regeneration. After birth, cardiomyocytes stop dividing and subsequently renew at a rate of about 1% per year. However, when the mechanical load is reduced, such as in patients supported by left ventricular assist devices, cardiomyocytes once again show signs of proliferation.

This observation prompted researchers to investigate whether the same mechanical load that restrains normal cardiac cells might also suppress cancer growth.

More Load, Less Growth

To investigate this question, researchers introduced two genetic alterations commonly found in human cancers, activation of the KRAS oncogene and loss of the TP53, into the liver, skeletal muscle, and hearts of mice. Tumors developed in multiple organs, but not in the heart.

The researchers then used a heterotopic heart transplant model in which a donor mouse’s heart is surgically connected to the neck (cervical) or abdominal vessels of a recipient mouse. The transplanted heart remained perfused but lost its normal mechanical loading (constant beating).

When researchers injected lung adenocarcinoma cells into 2 different hearts of the same animal, they observed entirely different outcomes. The cancer cells did not grow in the native mechanically loaded heart. However, the same cells grew rapidly and extensively in the mechanically unloaded transplanted heart.

Tumor cells had replaced nearly all normal tissue in the unloaded heart, whereas they occupied only approximately 20% of the ventricle in the native heart in 14 days. This difference could not be explained by differences in the initial tumor engraftment or cell death. Instead, the findings pointed to substantial differences in tumor cell proliferation.

Similar results were observed in bioengineered cardiac tissues exposed to varying degrees of mechanical stress. Tumor cells proliferated under conditions of low mechanical load but ceased proliferating as the mechanical load increased. Tumor growth was lowest in regions exposed to the greatest mechanical stimulation of cardiomyocytes in vitro.

However, the possibility of metabolic competition between cardiac and tumor cells for nutrition was ruled out.

From Mechanics to Genes

Next, we examined the influence of mechanical forces on tumor cell behavior.

Gene expression analyses of both human cardiac metastases and mouse tumor cells showed that mechanical stimulation altered chromatin accessibility through the activation of genes involved in chromatin remodeling. These changes promoted the expression of genes that suppress cell division.

The study also identified Nesprin-2, a part of the linker of the nucleoskeleton and cytoskeleton complex, which acts as a physical bridge. It is a multitasking protein that connects the cell’s outer structural network (cytoskeleton) to its inner genetic storage (nucleus) and appears to play a significant role in converting mechanical signals into changes in gene expression.

When Nesprin-2 was inactivated, cancer cells resumed proliferation despite exposure to a mechanical load, both in engineered tissues and animal models.

“Collectively, these results shed light on the role of mechanical forces in protecting the heart from cancer and may pave the way to cancer therapies based on mechanical stimulation,” concluded the authors.

An Actively Protected Organ

Speaking with Univadis Italy, part of the Medscape Professional Network, Giorgio Scita, PhD, director of the Mechanisms of Tumor Cell Migration research unit at AIRC Institute of Molecular Oncology and professor of general pathology at the University of Milan in Milan, Italy, said, “The study addressed a simple but fundamental question: Why is the heart largely resistant to cancer despite being highly vascularized and continuously exposed to circulating tumor cells?

These findings suggest that the heartbeat itself creates a mechanical environment that is hostile to tumor growth. The compressive forces generated by rhythmic myocardial contraction are sensed by cancer cells and translated into biochemical signals that limit their proliferation.

In this view, the heart is not simply an organ that is unfavorable for cancer growth but a tissue actively protected by its own mechanical forces.”

Speaking with Univadis Italy, Serena Zacchigna, PhD, study coauthor and head of the Cardiovascular Biology Laboratory at the International Centre for Genetic Engineering and Biotechnology, Trieste, Italy, said, “Until now, however, attention had focused primarily on signals from the extracellular matrix, such as tissue stiffness. Our study adds a new element: even forces generated directly by the movement of an organ — in this case, cardiac contraction — can influence the growth of cancer cells.”

Beyond the Heart

Scita said the findings have implications that extend well beyond the heart.

“The most significant aspect is that this work identifies tissue mechanics as an active regulator of tumor behavior,” he said. Stiffness, compression, tension, and confinement are not merely consequences of tumor growth, but factors capable of influencing proliferation, invasion, and dormancy.

The concept may apply to many solid tumors. Scita noted that cancer cells growing in confined environments, such as ductal carcinoma in situ of the breast, are exposed to substantial mechanical constraints. Understanding why some tumor cells remain susceptible to these forces whereas others evade them and become invasive remains a major unanswered question in cancer biology.

Research on these mechanisms is expanding internationally and in Italy as well. One example is the AIRC “5 per mille” (5 per thousand) research programs on metastatic disease, which includes projects designed to clarify how the mechanical properties of tumor tissue influence cancer initiation, metastatic spread, and disease progression.

Therapeutic Potential

According to Zacchigna, these findings open 2 principal avenues for future research.

“The first focuses on mechanical stimulation itself. In collaboration with engineers at the University of Siena, including a group led by Domenico Prattichizzo, researchers are developing wearable robotic devices designed to mimic the heartbeat and deliver mechanical stimulation to superficial solid tumors such as certain skin cancers.

The second approach is pharmacology. Researchers are investigating whether epigenetic therapies capable of modifying chromatin remodeling can reproduce the effects of cardiac contraction and suppress tumor cell proliferation.

However, Zacchigna cautioned that this work remains at an early experimental phase.”

However, before therapeutic applications can be pursued, important mechanistic questions remain unanswered.

Zacchigna noted that although the linker of nucleoskeleton and cytoskeleton (LINC) complex and Nesprin-2 are involved in signal transduction leading to chromatin reorganization and activation of cell cycle inhibitory loci, the molecular intermediates involved have yet to be fully defined.

Researchers also need to determine which genes are most critical, whether the mechanism operates across different tumor types, and whether it can be safely manipulated for therapeutic purposes.

In an accompanying commentary published in Science, Wyatt G. Paltzer, PhD, and James F. Martin, MD, from the Department of Integrative Physiology at the Baylor College of Medicine in Houston, noted that the findings suggest enhancing LINC complex activity could potentially suppress tumor growth.

However, because the complex has broad biologic functions, it may prove difficult to target therapeutically. The authors suggested that future studies should focus on identifying proteins that interact with Nesprin-2 or other components of the LINC complex and play a more specific role in inhibiting cancer cell proliferation.

Looking Ahead

Despite these challenges, Scita said that the study’s conceptual significance is already clear.

“Even if therapeutic applications remain years away, the findings suggest that cancer may one day be targeted by altering how tumor cells perceive and interpret physical forces.”

Scita and Zacchigna reported having no relevant conflicts of interest.

This story was translated from Univadis Italy.

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

Oral nicotinamide was cost-effective for reducing keratinocyte carcinoma (KC) risk in US veterans with a history of the disease, according to an economic analysis of Veterans Health Administration (VHA) data.

The findings, published online June 10 in JAMA Dermatology, “support strong consideration of nicotinamide for KC prevention in high-risk populations like veterans, particularly given its safety and tolerability,” wrote senior author Rebecca I. Hartman, MD, chief of the Dermatology Section at VA Boston and assistant professor of dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and co-authors.

Nicotinamide supplementation is “not only a cost-effective and patient-centric strategy for KC prevention, but it also remains economically favorable under a range of assumptions and may become even more cost-effective under higher procedure costs and frequency,” noted the authors.

The analysis included 33,822 individuals from the VHA database, all with a history of one or more KCs, including those with nicotinamide exposure for 30 or more days (n = 12,287) and those without that exposure (n = 21,535).

The mean ages in the unexposed and exposed cohorts were 76.9 and 77.2 years, respectively, and 98% were men. Procedural US VHA costs for KC treatment were estimated from previous research and adjusted for inflation. Nicotinamide pricing was obtained from the VHA.

KC incidence among nicotinamide-exposed and unexposed individuals was 0.204 and 0.255 events per person-year, respectively, reflecting an absolute risk reduction of 0.051 and 624 KCs prevented annually with nicotinamide supplementation.

With an estimated cost of $843 per KC, the yearly KC treatment expense was estimated at approximately $2.64 million, and the annual nicotinamide cost was estimated at $161,451, resulting in net savings of $364,581 — a 19.9% reduction in cohort-specific costs.

Assuming a quality-adjusted life-year (QALY) decrement of -0.01 per KC, nicotinamide use yielded an annual gain of 6.24 QALYs across the cohort and a savings of $58,426 per QALY gained.

A calculation of non-VHA cost-effectiveness, estimated with civilian prices and distributions, showed savings of $14,407 per QALY gained.

The authors concluded that oral nicotinamide was “a cost-effective and patient-centric preventive approach for KC, particularly in individuals with KC history at high risk of multiple primary KC.”

In an accompanying editorial, Ivo Abraham, PhD, JAMA Dermatology’s associate editor for quantitative methods and chief scientist at Matrix45, a health economics research and consulting group in Tucson, Arizona, and co-authors noted that although nicotinamide “is inexpensive, widely available, and mechanistically plausible for chemoprevention of actinic keratoses and KCs…stronger evidence remains required to support clinical recommendations.”

“Broader nicotinamide implementation might impart substantial population health benefits and cost savings to the VHA,” they wrote, while also asking, “do we truly know whether nicotinamide is effective for KC chemoprevention in broader populations?” They suggested that only an adequately powered randomized clinical trial in representative nonimmunosuppressed populations would provide the answer.

“Additional randomized controlled trials in non-VHA populations would provide further insight into generalizability beyond the VA healthcare system,” Hartman told Medscape Medical News.

“We are aiming to conduct a large [randomized controlled trial] in the VA to provide a more definitive answer,” added Lee Wheless, MD, one of Hartman’s coauthors, from Vanderbilt University Medical Center and the Tennessee Valley Healthcare System VA Medical Center, both in Nashville, Tennessee. “Doing so would also give a much better estimate of any potential side effects, though we and others have found no increased rate, and sometimes even a decreased rate, of major adverse cardiovascular events.”

Sarah Arron, MD, dermatologic surgeon with Palo Alto Foundation Medical Group in Palo Alto, California, and Premier Aesthetic Dermatology in San Carlos, California, who was not involved in the research, said, “It is gratifying to see that in the veteran population, nicotinamide affords protection against nonmelanoma skin cancer and is a cost-effective intervention. For a healthcare system such as the VHA, providing this over-the-counter vitamin through pharmacy benefits is an excellent method for reducing the overall cost of skin cancer treatment.”

Although Arron agreed that a randomized trial would offer a higher level of evidence for this intervention, she said the real-world obstacle is that nicotinamide is such an easily available, low-cost vitamin with a high safety profile. “Patients are not likely to sign up for a possible placebo when they can purchase nicotinamide online or at the drugstore,” she said. “This was reflected in Australia; once the positive data from the ONTRAC trial was publicized, investigators on the ONTRANS trial had difficulty enrolling patients because they were already taking the vitamin. The second study closed without meeting its enrollment goals and thus did not have power to show statistical significance.”

Hartman is supported by the US Department of Defense and the US Department of Veterans Affairs. Wheless is also supported by the US Department of Veterans Affairs. Arron is a speaker for Regeneron and Castle Biosciences; a consultant for Regeneron, Replimune, Castle, Lumenis, and Enspectra Health; an unpaid ambassador for HarkenDerm, which makes sunscreen as well as a sun and eye health supplement that includes nicotinamide as one of the ingredients.

The study authors reported having no conflicts of interest. Of the editorial authors, Abraham disclosed owning stock in Matrix45, which has received contract funding from companies outside this work, one author had disclosures not related to the work, and the third author had no disclosures.

Kate Johnson is a Montreal-based freelance medical journalist who has been writing for > 30 years about all areas of medicine.

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

Oral nicotinamide was cost-effective for reducing keratinocyte carcinoma (KC) risk in US veterans with a history of the disease, according to an economic analysis of Veterans Health Administration (VHA) data.

The findings, published online June 10 in JAMA Dermatology, “support strong consideration of nicotinamide for KC prevention in high-risk populations like veterans, particularly given its safety and tolerability,” wrote senior author Rebecca I. Hartman, MD, chief of the Dermatology Section at VA Boston and assistant professor of dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and co-authors.

Nicotinamide supplementation is “not only a cost-effective and patient-centric strategy for KC prevention, but it also remains economically favorable under a range of assumptions and may become even more cost-effective under higher procedure costs and frequency,” noted the authors.

The analysis included 33,822 individuals from the VHA database, all with a history of one or more KCs, including those with nicotinamide exposure for 30 or more days (n = 12,287) and those without that exposure (n = 21,535).

The mean ages in the unexposed and exposed cohorts were 76.9 and 77.2 years, respectively, and 98% were men. Procedural US VHA costs for KC treatment were estimated from previous research and adjusted for inflation. Nicotinamide pricing was obtained from the VHA.

KC incidence among nicotinamide-exposed and unexposed individuals was 0.204 and 0.255 events per person-year, respectively, reflecting an absolute risk reduction of 0.051 and 624 KCs prevented annually with nicotinamide supplementation.

With an estimated cost of $843 per KC, the yearly KC treatment expense was estimated at approximately $2.64 million, and the annual nicotinamide cost was estimated at $161,451, resulting in net savings of $364,581 — a 19.9% reduction in cohort-specific costs.

Assuming a quality-adjusted life-year (QALY) decrement of -0.01 per KC, nicotinamide use yielded an annual gain of 6.24 QALYs across the cohort and a savings of $58,426 per QALY gained.

A calculation of non-VHA cost-effectiveness, estimated with civilian prices and distributions, showed savings of $14,407 per QALY gained.

The authors concluded that oral nicotinamide was “a cost-effective and patient-centric preventive approach for KC, particularly in individuals with KC history at high risk of multiple primary KC.”

In an accompanying editorial, Ivo Abraham, PhD, JAMA Dermatology’s associate editor for quantitative methods and chief scientist at Matrix45, a health economics research and consulting group in Tucson, Arizona, and co-authors noted that although nicotinamide “is inexpensive, widely available, and mechanistically plausible for chemoprevention of actinic keratoses and KCs…stronger evidence remains required to support clinical recommendations.”

“Broader nicotinamide implementation might impart substantial population health benefits and cost savings to the VHA,” they wrote, while also asking, “do we truly know whether nicotinamide is effective for KC chemoprevention in broader populations?” They suggested that only an adequately powered randomized clinical trial in representative nonimmunosuppressed populations would provide the answer.

“Additional randomized controlled trials in non-VHA populations would provide further insight into generalizability beyond the VA healthcare system,” Hartman told Medscape Medical News.

“We are aiming to conduct a large [randomized controlled trial] in the VA to provide a more definitive answer,” added Lee Wheless, MD, one of Hartman’s coauthors, from Vanderbilt University Medical Center and the Tennessee Valley Healthcare System VA Medical Center, both in Nashville, Tennessee. “Doing so would also give a much better estimate of any potential side effects, though we and others have found no increased rate, and sometimes even a decreased rate, of major adverse cardiovascular events.”

Sarah Arron, MD, dermatologic surgeon with Palo Alto Foundation Medical Group in Palo Alto, California, and Premier Aesthetic Dermatology in San Carlos, California, who was not involved in the research, said, “It is gratifying to see that in the veteran population, nicotinamide affords protection against nonmelanoma skin cancer and is a cost-effective intervention. For a healthcare system such as the VHA, providing this over-the-counter vitamin through pharmacy benefits is an excellent method for reducing the overall cost of skin cancer treatment.”

Although Arron agreed that a randomized trial would offer a higher level of evidence for this intervention, she said the real-world obstacle is that nicotinamide is such an easily available, low-cost vitamin with a high safety profile. “Patients are not likely to sign up for a possible placebo when they can purchase nicotinamide online or at the drugstore,” she said. “This was reflected in Australia; once the positive data from the ONTRAC trial was publicized, investigators on the ONTRANS trial had difficulty enrolling patients because they were already taking the vitamin. The second study closed without meeting its enrollment goals and thus did not have power to show statistical significance.”

Hartman is supported by the US Department of Defense and the US Department of Veterans Affairs. Wheless is also supported by the US Department of Veterans Affairs. Arron is a speaker for Regeneron and Castle Biosciences; a consultant for Regeneron, Replimune, Castle, Lumenis, and Enspectra Health; an unpaid ambassador for HarkenDerm, which makes sunscreen as well as a sun and eye health supplement that includes nicotinamide as one of the ingredients.

The study authors reported having no conflicts of interest. Of the editorial authors, Abraham disclosed owning stock in Matrix45, which has received contract funding from companies outside this work, one author had disclosures not related to the work, and the third author had no disclosures.

Kate Johnson is a Montreal-based freelance medical journalist who has been writing for > 30 years about all areas of medicine.

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

Oral nicotinamide was cost-effective for reducing keratinocyte carcinoma (KC) risk in US veterans with a history of the disease, according to an economic analysis of Veterans Health Administration (VHA) data.

The findings, published online June 10 in JAMA Dermatology, “support strong consideration of nicotinamide for KC prevention in high-risk populations like veterans, particularly given its safety and tolerability,” wrote senior author Rebecca I. Hartman, MD, chief of the Dermatology Section at VA Boston and assistant professor of dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and co-authors.

Nicotinamide supplementation is “not only a cost-effective and patient-centric strategy for KC prevention, but it also remains economically favorable under a range of assumptions and may become even more cost-effective under higher procedure costs and frequency,” noted the authors.

The analysis included 33,822 individuals from the VHA database, all with a history of one or more KCs, including those with nicotinamide exposure for 30 or more days (n = 12,287) and those without that exposure (n = 21,535).

The mean ages in the unexposed and exposed cohorts were 76.9 and 77.2 years, respectively, and 98% were men. Procedural US VHA costs for KC treatment were estimated from previous research and adjusted for inflation. Nicotinamide pricing was obtained from the VHA.

KC incidence among nicotinamide-exposed and unexposed individuals was 0.204 and 0.255 events per person-year, respectively, reflecting an absolute risk reduction of 0.051 and 624 KCs prevented annually with nicotinamide supplementation.

With an estimated cost of $843 per KC, the yearly KC treatment expense was estimated at approximately $2.64 million, and the annual nicotinamide cost was estimated at $161,451, resulting in net savings of $364,581 — a 19.9% reduction in cohort-specific costs.

Assuming a quality-adjusted life-year (QALY) decrement of -0.01 per KC, nicotinamide use yielded an annual gain of 6.24 QALYs across the cohort and a savings of $58,426 per QALY gained.

A calculation of non-VHA cost-effectiveness, estimated with civilian prices and distributions, showed savings of $14,407 per QALY gained.

The authors concluded that oral nicotinamide was “a cost-effective and patient-centric preventive approach for KC, particularly in individuals with KC history at high risk of multiple primary KC.”

In an accompanying editorial, Ivo Abraham, PhD, JAMA Dermatology’s associate editor for quantitative methods and chief scientist at Matrix45, a health economics research and consulting group in Tucson, Arizona, and co-authors noted that although nicotinamide “is inexpensive, widely available, and mechanistically plausible for chemoprevention of actinic keratoses and KCs…stronger evidence remains required to support clinical recommendations.”

“Broader nicotinamide implementation might impart substantial population health benefits and cost savings to the VHA,” they wrote, while also asking, “do we truly know whether nicotinamide is effective for KC chemoprevention in broader populations?” They suggested that only an adequately powered randomized clinical trial in representative nonimmunosuppressed populations would provide the answer.

“Additional randomized controlled trials in non-VHA populations would provide further insight into generalizability beyond the VA healthcare system,” Hartman told Medscape Medical News.

“We are aiming to conduct a large [randomized controlled trial] in the VA to provide a more definitive answer,” added Lee Wheless, MD, one of Hartman’s coauthors, from Vanderbilt University Medical Center and the Tennessee Valley Healthcare System VA Medical Center, both in Nashville, Tennessee. “Doing so would also give a much better estimate of any potential side effects, though we and others have found no increased rate, and sometimes even a decreased rate, of major adverse cardiovascular events.”

Sarah Arron, MD, dermatologic surgeon with Palo Alto Foundation Medical Group in Palo Alto, California, and Premier Aesthetic Dermatology in San Carlos, California, who was not involved in the research, said, “It is gratifying to see that in the veteran population, nicotinamide affords protection against nonmelanoma skin cancer and is a cost-effective intervention. For a healthcare system such as the VHA, providing this over-the-counter vitamin through pharmacy benefits is an excellent method for reducing the overall cost of skin cancer treatment.”

Although Arron agreed that a randomized trial would offer a higher level of evidence for this intervention, she said the real-world obstacle is that nicotinamide is such an easily available, low-cost vitamin with a high safety profile. “Patients are not likely to sign up for a possible placebo when they can purchase nicotinamide online or at the drugstore,” she said. “This was reflected in Australia; once the positive data from the ONTRAC trial was publicized, investigators on the ONTRANS trial had difficulty enrolling patients because they were already taking the vitamin. The second study closed without meeting its enrollment goals and thus did not have power to show statistical significance.”

Hartman is supported by the US Department of Defense and the US Department of Veterans Affairs. Wheless is also supported by the US Department of Veterans Affairs. Arron is a speaker for Regeneron and Castle Biosciences; a consultant for Regeneron, Replimune, Castle, Lumenis, and Enspectra Health; an unpaid ambassador for HarkenDerm, which makes sunscreen as well as a sun and eye health supplement that includes nicotinamide as one of the ingredients.

The study authors reported having no conflicts of interest. Of the editorial authors, Abraham disclosed owning stock in Matrix45, which has received contract funding from companies outside this work, one author had disclosures not related to the work, and the third author had no disclosures.

Kate Johnson is a Montreal-based freelance medical journalist who has been writing for > 30 years about all areas of medicine.

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