News

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.

Offering lung cancer screening to everyone with a 20-year smoking history could expand access to screening, identify more cancers, and reduce disparities, new research suggests.

In an analysis of nearly 1 million US veterans, researchers estimated that a simplified approach to lung cancer screening — based on smoking duration rather than pack-years — would expand screening eligibility by nearly 30% and reduce potentially missed lung cancers by over 70%.

Those shifts would be especially pronounced among women and Black individuals — 2 groups that are underserved by current screening criteria.

The results, presented at the American Society of Clinical Oncology (ASCO) 2026, come at a time when some groups are revisiting their lung cancer screening guidelines.

And they support smoking duration as a “simpler, more sensitive, and more equitable metric for screening eligibility,” researcher Brendan T. Heiden, MD, MPHS, Washington University School of Medicine in St. Louis, St. Louis, told meeting attendees.

Toward a Better Metric

Current guidelines from the US Preventive Services Task Force (USPSTF) recommend annual lung cancer screening with low-dose CT for adults aged 50-80 years who have at least a 20 pack-year smoking history and either currently smoke or quit within the past 15 years.

The 20 pack-year metric is equivalent to smoking a pack of cigarettes per day for 20 years. Because it requires patients to remember their smoking intensity over decades, it can be challenging to calculate and translate into care, Heiden said.

As it stands, few Americans who are eligible under current USPSTF guidelines actually undergo lung cancer screening, at about 15%-20%, Heiden noted. Meanwhile, mounting evidence suggests that many lung cancers occur in individuals who never meet those eligibility criteria.

Boosting screening uptake, Heiden said, is not enough: There’s a need to revisit eligibility itself to reach more high-risk individuals.

Some groups are already taking steps in that direction. Recently updated guidelines from the National Comprehensive Cancer Network (NCCN) added a category 2B recommendation supporting screening for individuals with at least a 20-year smoking history, regardless of pack-years. (The guidelines also say former smokers are eligible no matter how long ago they quit.)

For their study, Heiden’s team sought to estimate the performance of that smoking-duration metric against current USPSTF pack-year criteria. They used Veterans Health Administration data on over 980,000 veterans whose smoking histories were prospectively collected; lung cancer diagnoses were identified through the Veterans Affairs Central Cancer Registry.

Most of the included veterans (67%) had a smoking history; their mean age was 64 years, and 21% were Black.

Overall, the researchers found that basing eligibility on 20-year smoking duration would substantially expand access to screening: Among veterans with a smoking history, 68% qualified for screening under current USPSTF criteria compared with 87% using the smoking-duration approach.

The gains were especially pronounced among women and Black individuals (who, based on prior research, typically smoke less intensely than White males). Under USPSTF criteria, only about 55% of female and Black veterans qualified for screening compared with 83% for both groups under the smoking-duration criterion.

Importantly, Heiden said, people meeting the smoking-duration threshold remained at substantially elevated risk for lung cancer, suggesting the broader screening criteria were not merely capturing low-risk smokers.

The 5-year lung cancer incidence among veterans eligible under the smoking-duration approach was 1.59% — 11 times the rate of 0.14% among never smokers.

Perhaps most striking, Heiden said, the proportion of potentially missed cancers dropped from 13% with the pack-year metric to just 4% using the smoking-duration metric — a relative reduction of more than 70%.

Again, women and Black individuals would see the largest gains: Among Black veterans, potentially missed cancers fell from 25% to 6%, whereas among female veterans they declined from 22% to 7%.

Optimal Approach Still Unclear

The analysis had limitations, including a predominantly male veteran population whose smoking exposure was far greater than that of the general US population, indicating high inherent lung cancer risk.

But the results support what the NCCN has already done, according to Mary Reid, PhD, MSPH, BSN, a member of the group’s lung cancer screening guideline panel and chief of cancer screening, survivorship and mentorship at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

“Doing the calculation for pack-years can be difficult,” Reid told Medscape Medical News. “Smoking duration is easier to calculate and really the way to go.”

The USPSTF does not comment on individual studies outside of its recommendation development process.

At the meeting, study discussant Katharine A. Rendle, PhD, called the work “impressive,” citing the size of the cohort and strength of the data.

It’s particularly noteworthy that the simpler screening criteria improved sensitivity for all veterans, while largely eliminating disparities, according to Rendle, of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Still, she said, further research could better define the optimal screening strategy.

“Smoking duration is a promising approach, but in my opinion, guidelines likely need to account for the underlying risk in the population,” Rendle said, noting that current smoking prevalence in the US population is about 10%.

She suggested future studies consider other smoking-duration thresholds, such as 30 or 40 years, and look at other outcomes, including life-years gained.

“It’s critical that we prioritize strategies that maximize potential benefit from screening — not just identify those at lung cancer risk — given downstream costs and burden on populations and health care systems,” Rendle said.

The study had no commercial funding. Heiden, Rendle, and Reid had no relevant disclosures.

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

Offering lung cancer screening to everyone with a 20-year smoking history could expand access to screening, identify more cancers, and reduce disparities, new research suggests.

In an analysis of nearly 1 million US veterans, researchers estimated that a simplified approach to lung cancer screening — based on smoking duration rather than pack-years — would expand screening eligibility by nearly 30% and reduce potentially missed lung cancers by over 70%.

Those shifts would be especially pronounced among women and Black individuals — 2 groups that are underserved by current screening criteria.

The results, presented at the American Society of Clinical Oncology (ASCO) 2026, come at a time when some groups are revisiting their lung cancer screening guidelines.

And they support smoking duration as a “simpler, more sensitive, and more equitable metric for screening eligibility,” researcher Brendan T. Heiden, MD, MPHS, Washington University School of Medicine in St. Louis, St. Louis, told meeting attendees.

Toward a Better Metric

Current guidelines from the US Preventive Services Task Force (USPSTF) recommend annual lung cancer screening with low-dose CT for adults aged 50-80 years who have at least a 20 pack-year smoking history and either currently smoke or quit within the past 15 years.

The 20 pack-year metric is equivalent to smoking a pack of cigarettes per day for 20 years. Because it requires patients to remember their smoking intensity over decades, it can be challenging to calculate and translate into care, Heiden said.

As it stands, few Americans who are eligible under current USPSTF guidelines actually undergo lung cancer screening, at about 15%-20%, Heiden noted. Meanwhile, mounting evidence suggests that many lung cancers occur in individuals who never meet those eligibility criteria.

Boosting screening uptake, Heiden said, is not enough: There’s a need to revisit eligibility itself to reach more high-risk individuals.

Some groups are already taking steps in that direction. Recently updated guidelines from the National Comprehensive Cancer Network (NCCN) added a category 2B recommendation supporting screening for individuals with at least a 20-year smoking history, regardless of pack-years. (The guidelines also say former smokers are eligible no matter how long ago they quit.)

For their study, Heiden’s team sought to estimate the performance of that smoking-duration metric against current USPSTF pack-year criteria. They used Veterans Health Administration data on over 980,000 veterans whose smoking histories were prospectively collected; lung cancer diagnoses were identified through the Veterans Affairs Central Cancer Registry.

Most of the included veterans (67%) had a smoking history; their mean age was 64 years, and 21% were Black.

Overall, the researchers found that basing eligibility on 20-year smoking duration would substantially expand access to screening: Among veterans with a smoking history, 68% qualified for screening under current USPSTF criteria compared with 87% using the smoking-duration approach.

The gains were especially pronounced among women and Black individuals (who, based on prior research, typically smoke less intensely than White males). Under USPSTF criteria, only about 55% of female and Black veterans qualified for screening compared with 83% for both groups under the smoking-duration criterion.

Importantly, Heiden said, people meeting the smoking-duration threshold remained at substantially elevated risk for lung cancer, suggesting the broader screening criteria were not merely capturing low-risk smokers.

The 5-year lung cancer incidence among veterans eligible under the smoking-duration approach was 1.59% — 11 times the rate of 0.14% among never smokers.

Perhaps most striking, Heiden said, the proportion of potentially missed cancers dropped from 13% with the pack-year metric to just 4% using the smoking-duration metric — a relative reduction of more than 70%.

Again, women and Black individuals would see the largest gains: Among Black veterans, potentially missed cancers fell from 25% to 6%, whereas among female veterans they declined from 22% to 7%.

Optimal Approach Still Unclear

The analysis had limitations, including a predominantly male veteran population whose smoking exposure was far greater than that of the general US population, indicating high inherent lung cancer risk.

But the results support what the NCCN has already done, according to Mary Reid, PhD, MSPH, BSN, a member of the group’s lung cancer screening guideline panel and chief of cancer screening, survivorship and mentorship at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

“Doing the calculation for pack-years can be difficult,” Reid told Medscape Medical News. “Smoking duration is easier to calculate and really the way to go.”

The USPSTF does not comment on individual studies outside of its recommendation development process.

At the meeting, study discussant Katharine A. Rendle, PhD, called the work “impressive,” citing the size of the cohort and strength of the data.

It’s particularly noteworthy that the simpler screening criteria improved sensitivity for all veterans, while largely eliminating disparities, according to Rendle, of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Still, she said, further research could better define the optimal screening strategy.

“Smoking duration is a promising approach, but in my opinion, guidelines likely need to account for the underlying risk in the population,” Rendle said, noting that current smoking prevalence in the US population is about 10%.

She suggested future studies consider other smoking-duration thresholds, such as 30 or 40 years, and look at other outcomes, including life-years gained.

“It’s critical that we prioritize strategies that maximize potential benefit from screening — not just identify those at lung cancer risk — given downstream costs and burden on populations and health care systems,” Rendle said.

The study had no commercial funding. Heiden, Rendle, and Reid had no relevant disclosures.

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

Offering lung cancer screening to everyone with a 20-year smoking history could expand access to screening, identify more cancers, and reduce disparities, new research suggests.

In an analysis of nearly 1 million US veterans, researchers estimated that a simplified approach to lung cancer screening — based on smoking duration rather than pack-years — would expand screening eligibility by nearly 30% and reduce potentially missed lung cancers by over 70%.

Those shifts would be especially pronounced among women and Black individuals — 2 groups that are underserved by current screening criteria.

The results, presented at the American Society of Clinical Oncology (ASCO) 2026, come at a time when some groups are revisiting their lung cancer screening guidelines.

And they support smoking duration as a “simpler, more sensitive, and more equitable metric for screening eligibility,” researcher Brendan T. Heiden, MD, MPHS, Washington University School of Medicine in St. Louis, St. Louis, told meeting attendees.

Toward a Better Metric

Current guidelines from the US Preventive Services Task Force (USPSTF) recommend annual lung cancer screening with low-dose CT for adults aged 50-80 years who have at least a 20 pack-year smoking history and either currently smoke or quit within the past 15 years.

The 20 pack-year metric is equivalent to smoking a pack of cigarettes per day for 20 years. Because it requires patients to remember their smoking intensity over decades, it can be challenging to calculate and translate into care, Heiden said.

As it stands, few Americans who are eligible under current USPSTF guidelines actually undergo lung cancer screening, at about 15%-20%, Heiden noted. Meanwhile, mounting evidence suggests that many lung cancers occur in individuals who never meet those eligibility criteria.

Boosting screening uptake, Heiden said, is not enough: There’s a need to revisit eligibility itself to reach more high-risk individuals.

Some groups are already taking steps in that direction. Recently updated guidelines from the National Comprehensive Cancer Network (NCCN) added a category 2B recommendation supporting screening for individuals with at least a 20-year smoking history, regardless of pack-years. (The guidelines also say former smokers are eligible no matter how long ago they quit.)

For their study, Heiden’s team sought to estimate the performance of that smoking-duration metric against current USPSTF pack-year criteria. They used Veterans Health Administration data on over 980,000 veterans whose smoking histories were prospectively collected; lung cancer diagnoses were identified through the Veterans Affairs Central Cancer Registry.

Most of the included veterans (67%) had a smoking history; their mean age was 64 years, and 21% were Black.

Overall, the researchers found that basing eligibility on 20-year smoking duration would substantially expand access to screening: Among veterans with a smoking history, 68% qualified for screening under current USPSTF criteria compared with 87% using the smoking-duration approach.

The gains were especially pronounced among women and Black individuals (who, based on prior research, typically smoke less intensely than White males). Under USPSTF criteria, only about 55% of female and Black veterans qualified for screening compared with 83% for both groups under the smoking-duration criterion.

Importantly, Heiden said, people meeting the smoking-duration threshold remained at substantially elevated risk for lung cancer, suggesting the broader screening criteria were not merely capturing low-risk smokers.

The 5-year lung cancer incidence among veterans eligible under the smoking-duration approach was 1.59% — 11 times the rate of 0.14% among never smokers.

Perhaps most striking, Heiden said, the proportion of potentially missed cancers dropped from 13% with the pack-year metric to just 4% using the smoking-duration metric — a relative reduction of more than 70%.

Again, women and Black individuals would see the largest gains: Among Black veterans, potentially missed cancers fell from 25% to 6%, whereas among female veterans they declined from 22% to 7%.

Optimal Approach Still Unclear

The analysis had limitations, including a predominantly male veteran population whose smoking exposure was far greater than that of the general US population, indicating high inherent lung cancer risk.

But the results support what the NCCN has already done, according to Mary Reid, PhD, MSPH, BSN, a member of the group’s lung cancer screening guideline panel and chief of cancer screening, survivorship and mentorship at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

“Doing the calculation for pack-years can be difficult,” Reid told Medscape Medical News. “Smoking duration is easier to calculate and really the way to go.”

The USPSTF does not comment on individual studies outside of its recommendation development process.

At the meeting, study discussant Katharine A. Rendle, PhD, called the work “impressive,” citing the size of the cohort and strength of the data.

It’s particularly noteworthy that the simpler screening criteria improved sensitivity for all veterans, while largely eliminating disparities, according to Rendle, of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Still, she said, further research could better define the optimal screening strategy.

“Smoking duration is a promising approach, but in my opinion, guidelines likely need to account for the underlying risk in the population,” Rendle said, noting that current smoking prevalence in the US population is about 10%.

She suggested future studies consider other smoking-duration thresholds, such as 30 or 40 years, and look at other outcomes, including life-years gained.

“It’s critical that we prioritize strategies that maximize potential benefit from screening — not just identify those at lung cancer risk — given downstream costs and burden on populations and health care systems,” Rendle said.

The study had no commercial funding. Heiden, Rendle, and Reid had no relevant disclosures.

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

A pharmacist-driven Veterans Health Administration (VHA) care program for veterans recovering from hospital visits for chronic obstructive pulmonary disease (COPD) is helping reduce symptom burden, a new retrospective cohort study finds. 

Of 286 patients with COPD who participated in the program and reported outcomes, 62.6% said their symptoms improved, 28.7% said they had no change, and 8.7% reported worsening symptoms, according to Edward Portillo, PharmD, and colleagues in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. Patients whose medications were changed by VHA pharmacists with prescribing authority were more likely to experience clinically meaningful improvement in symptoms compared to those without this medication change (66.3% vs. 46.6%, respectively, P < .001).

“If you had a debilitating lung disease that was affecting your ability to breathe all day, affected your ability to go to the grocery store, made it hard for you to see your grandkids, and all of a sudden you had this visit and a month to 2 months later reported feeling a heck of a lot better—that’s a really big deal,” Portillo said in an interview with Federal Practitioner. 

COPD, a progressive and irreversible lung disease that encompasses emphysema and chronic bronchitis, is the fifth-leading cause of death in the US according to the most recently available data. Research has suggested that many patients do not receive guidance-concordant care. 

“The prevalence of COPD among our veteran population is threefold greater than in the civilian population, and 1 in 4 veterans have a COPD diagnosis,” noted Portillo a pharmacist at the William S. Middleton Veterans Affairs (VA) Hospital and an associate professor at the University of Wisconsin, Madison School of Pharmacy.

In 2015, Portillo developed a program called COPD Coordinated Access to Reduce Exacerbations (COPD CARE). The program, now operating at 50 VA medical centers, allows pharmacists to optimize medication, order spirometry, assess symptoms, place referrals for pulmonary rehabilitation, and support inhaler adherence and tobacco cessation. The pharmacists work with other members of the patient care teams such as primary care physicians and nurses.

“It's integrated within the teams themselves that serve our veterans, which is very unique for a service like this,” Portillo said.

The program is especially beneficial for patients within their first 30 to 90 days posthospitalization when they may not normally be seen in the clinic, Portillo said.

“We use a national dashboard to identify patients who left the [emergency department] or hospital, and then we assess if they’d be appropriate candidates for the program,” he said. “Our goal is to see patients as fast as 30 days and as late as 90 days, but ideally within 30 to 60 days of discharge.”

An initial in-person visit of ≤ 30 minutes is followed by a 15-minute follow-up phone call in 30 days to see if interventions have been continued, he said. 

The study analyzed data from September 2020 to February 2024 from 28 VA medical centers that administer the COPD CARE program. All patients had an initial wellness visit within 90 days of hospitalization and 2 COPD Assessment Test (CAT) scores. Among 326 patients, the average age was 73.2 years; 95.7% were male; 77.9% were White, 15.6% were Black, and 2.1% had Hispanic ethnicity. 

At the time of the wellness visit, patients mean CAT score was 18.4. It improved to 15.2 by follow-up, with especially large improvements in limitations (2.5 to 2.0), tightness (1.7 to 1.2), cough (2.5 to 2.1), energy (2.9 to 2.5), phlegm (2.4 to 2.0), and sleep (1.9 to 1.5).

Pharmacists created 236 COPD action plans, changed 208 medications, provided 151 service referrals, identified 117 nonadherent patients, and identified 62 incorrect techniques. 

But only 1 intervention – medication change – was linked to clinically meaningful improvements in symptoms.

“This is not a disease that's easy to change symptomatically,” Portillo said. “My hope is that over time, and with multiple visits, those patients shift into a mode of ‘I am actually feeling much better now.’” 

Suzanne Bollmeier, PharmD, professor of Pharmacy Practice at the University of Health Sciences and Pharmacy in St. Louis, who is familiar with the study but did not take part in it, told Federal Practitioner that the results align with previous research.

Bollmeier mentioned several studies that link pharmacist interventions to better health outcomes, including inhalation technique and medication adherence.

“Pharmacists are well-positioned within the health care team to help care for patients with COPD,” she said. “Pharmacists can help with patient adherence, inhaler education, and reduction in disease risk but also identify drug-related problems and modify respiratory regimens to better optimize patient outcomes.”

Moving forward, she said, “it would be interesting to see what specific medication regimen changes were made in this present study that led to improvement in symptoms.”

The study was funded by the VA Office of Rural Health and the University of Wisconsin Institute for Clinical and Translational Research, which is supported by the National Center for Advancing Translational Sciences. The study authors and Bollmeier had no disclosures.

A pharmacist-driven Veterans Health Administration (VHA) care program for veterans recovering from hospital visits for chronic obstructive pulmonary disease (COPD) is helping reduce symptom burden, a new retrospective cohort study finds. 

Of 286 patients with COPD who participated in the program and reported outcomes, 62.6% said their symptoms improved, 28.7% said they had no change, and 8.7% reported worsening symptoms, according to Edward Portillo, PharmD, and colleagues in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. Patients whose medications were changed by VHA pharmacists with prescribing authority were more likely to experience clinically meaningful improvement in symptoms compared to those without this medication change (66.3% vs. 46.6%, respectively, P < .001).

“If you had a debilitating lung disease that was affecting your ability to breathe all day, affected your ability to go to the grocery store, made it hard for you to see your grandkids, and all of a sudden you had this visit and a month to 2 months later reported feeling a heck of a lot better—that’s a really big deal,” Portillo said in an interview with Federal Practitioner. 

COPD, a progressive and irreversible lung disease that encompasses emphysema and chronic bronchitis, is the fifth-leading cause of death in the US according to the most recently available data. Research has suggested that many patients do not receive guidance-concordant care. 

“The prevalence of COPD among our veteran population is threefold greater than in the civilian population, and 1 in 4 veterans have a COPD diagnosis,” noted Portillo a pharmacist at the William S. Middleton Veterans Affairs (VA) Hospital and an associate professor at the University of Wisconsin, Madison School of Pharmacy.

In 2015, Portillo developed a program called COPD Coordinated Access to Reduce Exacerbations (COPD CARE). The program, now operating at 50 VA medical centers, allows pharmacists to optimize medication, order spirometry, assess symptoms, place referrals for pulmonary rehabilitation, and support inhaler adherence and tobacco cessation. The pharmacists work with other members of the patient care teams such as primary care physicians and nurses.

“It's integrated within the teams themselves that serve our veterans, which is very unique for a service like this,” Portillo said.

The program is especially beneficial for patients within their first 30 to 90 days posthospitalization when they may not normally be seen in the clinic, Portillo said.

“We use a national dashboard to identify patients who left the [emergency department] or hospital, and then we assess if they’d be appropriate candidates for the program,” he said. “Our goal is to see patients as fast as 30 days and as late as 90 days, but ideally within 30 to 60 days of discharge.”

An initial in-person visit of ≤ 30 minutes is followed by a 15-minute follow-up phone call in 30 days to see if interventions have been continued, he said. 

The study analyzed data from September 2020 to February 2024 from 28 VA medical centers that administer the COPD CARE program. All patients had an initial wellness visit within 90 days of hospitalization and 2 COPD Assessment Test (CAT) scores. Among 326 patients, the average age was 73.2 years; 95.7% were male; 77.9% were White, 15.6% were Black, and 2.1% had Hispanic ethnicity. 

At the time of the wellness visit, patients mean CAT score was 18.4. It improved to 15.2 by follow-up, with especially large improvements in limitations (2.5 to 2.0), tightness (1.7 to 1.2), cough (2.5 to 2.1), energy (2.9 to 2.5), phlegm (2.4 to 2.0), and sleep (1.9 to 1.5).

Pharmacists created 236 COPD action plans, changed 208 medications, provided 151 service referrals, identified 117 nonadherent patients, and identified 62 incorrect techniques. 

But only 1 intervention – medication change – was linked to clinically meaningful improvements in symptoms.

“This is not a disease that's easy to change symptomatically,” Portillo said. “My hope is that over time, and with multiple visits, those patients shift into a mode of ‘I am actually feeling much better now.’” 

Suzanne Bollmeier, PharmD, professor of Pharmacy Practice at the University of Health Sciences and Pharmacy in St. Louis, who is familiar with the study but did not take part in it, told Federal Practitioner that the results align with previous research.

Bollmeier mentioned several studies that link pharmacist interventions to better health outcomes, including inhalation technique and medication adherence.

“Pharmacists are well-positioned within the health care team to help care for patients with COPD,” she said. “Pharmacists can help with patient adherence, inhaler education, and reduction in disease risk but also identify drug-related problems and modify respiratory regimens to better optimize patient outcomes.”

Moving forward, she said, “it would be interesting to see what specific medication regimen changes were made in this present study that led to improvement in symptoms.”

The study was funded by the VA Office of Rural Health and the University of Wisconsin Institute for Clinical and Translational Research, which is supported by the National Center for Advancing Translational Sciences. The study authors and Bollmeier had no disclosures.

A pharmacist-driven Veterans Health Administration (VHA) care program for veterans recovering from hospital visits for chronic obstructive pulmonary disease (COPD) is helping reduce symptom burden, a new retrospective cohort study finds. 

Of 286 patients with COPD who participated in the program and reported outcomes, 62.6% said their symptoms improved, 28.7% said they had no change, and 8.7% reported worsening symptoms, according to Edward Portillo, PharmD, and colleagues in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. Patients whose medications were changed by VHA pharmacists with prescribing authority were more likely to experience clinically meaningful improvement in symptoms compared to those without this medication change (66.3% vs. 46.6%, respectively, P < .001).

“If you had a debilitating lung disease that was affecting your ability to breathe all day, affected your ability to go to the grocery store, made it hard for you to see your grandkids, and all of a sudden you had this visit and a month to 2 months later reported feeling a heck of a lot better—that’s a really big deal,” Portillo said in an interview with Federal Practitioner. 

COPD, a progressive and irreversible lung disease that encompasses emphysema and chronic bronchitis, is the fifth-leading cause of death in the US according to the most recently available data. Research has suggested that many patients do not receive guidance-concordant care. 

“The prevalence of COPD among our veteran population is threefold greater than in the civilian population, and 1 in 4 veterans have a COPD diagnosis,” noted Portillo a pharmacist at the William S. Middleton Veterans Affairs (VA) Hospital and an associate professor at the University of Wisconsin, Madison School of Pharmacy.

In 2015, Portillo developed a program called COPD Coordinated Access to Reduce Exacerbations (COPD CARE). The program, now operating at 50 VA medical centers, allows pharmacists to optimize medication, order spirometry, assess symptoms, place referrals for pulmonary rehabilitation, and support inhaler adherence and tobacco cessation. The pharmacists work with other members of the patient care teams such as primary care physicians and nurses.

“It's integrated within the teams themselves that serve our veterans, which is very unique for a service like this,” Portillo said.

The program is especially beneficial for patients within their first 30 to 90 days posthospitalization when they may not normally be seen in the clinic, Portillo said.

“We use a national dashboard to identify patients who left the [emergency department] or hospital, and then we assess if they’d be appropriate candidates for the program,” he said. “Our goal is to see patients as fast as 30 days and as late as 90 days, but ideally within 30 to 60 days of discharge.”

An initial in-person visit of ≤ 30 minutes is followed by a 15-minute follow-up phone call in 30 days to see if interventions have been continued, he said. 

The study analyzed data from September 2020 to February 2024 from 28 VA medical centers that administer the COPD CARE program. All patients had an initial wellness visit within 90 days of hospitalization and 2 COPD Assessment Test (CAT) scores. Among 326 patients, the average age was 73.2 years; 95.7% were male; 77.9% were White, 15.6% were Black, and 2.1% had Hispanic ethnicity. 

At the time of the wellness visit, patients mean CAT score was 18.4. It improved to 15.2 by follow-up, with especially large improvements in limitations (2.5 to 2.0), tightness (1.7 to 1.2), cough (2.5 to 2.1), energy (2.9 to 2.5), phlegm (2.4 to 2.0), and sleep (1.9 to 1.5).

Pharmacists created 236 COPD action plans, changed 208 medications, provided 151 service referrals, identified 117 nonadherent patients, and identified 62 incorrect techniques. 

But only 1 intervention – medication change – was linked to clinically meaningful improvements in symptoms.

“This is not a disease that's easy to change symptomatically,” Portillo said. “My hope is that over time, and with multiple visits, those patients shift into a mode of ‘I am actually feeling much better now.’” 

Suzanne Bollmeier, PharmD, professor of Pharmacy Practice at the University of Health Sciences and Pharmacy in St. Louis, who is familiar with the study but did not take part in it, told Federal Practitioner that the results align with previous research.

Bollmeier mentioned several studies that link pharmacist interventions to better health outcomes, including inhalation technique and medication adherence.

“Pharmacists are well-positioned within the health care team to help care for patients with COPD,” she said. “Pharmacists can help with patient adherence, inhaler education, and reduction in disease risk but also identify drug-related problems and modify respiratory regimens to better optimize patient outcomes.”

Moving forward, she said, “it would be interesting to see what specific medication regimen changes were made in this present study that led to improvement in symptoms.”

The study was funded by the VA Office of Rural Health and the University of Wisconsin Institute for Clinical and Translational Research, which is supported by the National Center for Advancing Translational Sciences. The study authors and Bollmeier had no disclosures.

ORLANDO, Fla. — The Centers for Medicare & Medicaid Services (CMS) will not cover continuous positive airway pressure (CPAP) treatment for people who are nonadherent by 90 days. However, that requirement is too stringent, said researchers who found more than one third of adults who struggled with adherence initially still used the therapy 1 year later at levels associated with clinical benefit.

To test the requirement, investigators assessed 132,492 patients in the Kaiser Permanente Southern California system. The patients were issued CPAP devices to treat obstructive sleep apnea from 2015 to 2023. At 1 year, 36% who would have failed the CMS requirement were still using their CPAP.

The results counter CMS’ assumption that poor early CPAP use always leads to long-term abandonment, said Dennis Hwang, MD, co-chair of Sleep Medicine and medical director of the Sleep Disorders Center at Kaiser Permanente Southern California in Fontana, California.

"We should transition away from a one-size-fits-all definition of success," Hwang added at the American Thoracic Society (ATS) 2026 International Conference.

Background and Methodology

The 90-day adherence requirement does not only apply to Medicare or Medicaid recipients, Hwang said; many private insurers have adopted the same policy. In contrast, Kaiser Permanente Southern California does not restrict usage based on early adherence.

Hwang et al considered any Kaiser Permanente member with any CPAP usage during the 12 months after being issued a device an active user. They tracked mean nightly minutes of use and the percentage of nights with ≥ 2 and ≥ 4 hours of average use.

Overall, 49% would have met the CMS criteria and used the therapy ≥ 4 hours on average each night for 70% of nights during the first 90 days. Kaiser Permanente members aged ≥ 65 years were more compliant, with 54% meeting the CMS benchmarks. ATS guidelines recognize that even ≥ 2 hours of CPAP per night on average can confer some benefits.

The average age in the study was 55 years, and the mean apnea-hypopnea index was 32-33 events per hour, suggesting severe obstructive sleep apnea at baseline. The cohort was diverse, with 42% White, 35% Hispanic, 10% Black, 9% Asian, and 4% other race or ethnicity.

Key Findings

A total of 64,568 adults would have been CMS adherent at 90 days; investigators compared outcomes at 12 months with another 67,867 nonadherent adults.

There were some significant differences between groups. The mean age was 56.4 years vs 53.7 years in the adherent group vs the nonadherent group; men made up a greater proportion of the adherent group, 68.5% vs 62.6%; and the mean number of events per hour was 35 vs 30 (P < .001 for all).

Among the 90-day nonadherent group, about 21% met the 2-hour or greater adherence benchmark, and approximately 14% used CPAP an average of ≥ 4 hours.

“Still a substantial number of [non-CMS adherent] patients are using CPAP,” Hwang said.

Failure to meet CMS adherence was associated with younger age, female sex, non-White race or ethnicity, lower socioeconomic status, and lower severity of obstructive sleep apnea.

“There is also an equity dimension. Whites had better adherence rates during the first 90 days, so there is already a disparity here in terms of outcomes,” Hwang said. Policy changes could improve access to long-term therapy on a more equitable basis, he added. For example, a 2023 ATS policy statement calls for a more patient-centric approach and a focus on reducing inequities.

An Arbitrary Requirement

The 90-day requirement seems a little short, said session co-moderator Oren Cohen, MD, assistant professor in the Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine at Icahn School of Medicine at Mount Sinai in New York City, when asked to comment. “It can take longer to get a patient back into the clinic and go through a lot of the trial and error that it takes to do a mask fitting and adjust the pressures.”

If a patient is using their CPAP device for fewer than 4 hours a night in the early period, it doesn’t mean things are failing, Cohen said. “It’s just that you’ve got to keep trying and pushing forward.”

Nonetheless, there are some long-term noncompliant patients, Cohen said. “I certainly don’t think that somebody who’s not using the device for years should continue to hold on to it. That resource can be reallocated to somebody who would get more benefit from it. But I think setting a 90-day and 4-hour rule seems arbitrary…and there should be more leeway there.”

The study was independently supported.

Hwang and Cohen reported having no relevant financial disclosures.

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

ORLANDO, Fla. — The Centers for Medicare & Medicaid Services (CMS) will not cover continuous positive airway pressure (CPAP) treatment for people who are nonadherent by 90 days. However, that requirement is too stringent, said researchers who found more than one third of adults who struggled with adherence initially still used the therapy 1 year later at levels associated with clinical benefit.

To test the requirement, investigators assessed 132,492 patients in the Kaiser Permanente Southern California system. The patients were issued CPAP devices to treat obstructive sleep apnea from 2015 to 2023. At 1 year, 36% who would have failed the CMS requirement were still using their CPAP.

The results counter CMS’ assumption that poor early CPAP use always leads to long-term abandonment, said Dennis Hwang, MD, co-chair of Sleep Medicine and medical director of the Sleep Disorders Center at Kaiser Permanente Southern California in Fontana, California.

"We should transition away from a one-size-fits-all definition of success," Hwang added at the American Thoracic Society (ATS) 2026 International Conference.

Background and Methodology

The 90-day adherence requirement does not only apply to Medicare or Medicaid recipients, Hwang said; many private insurers have adopted the same policy. In contrast, Kaiser Permanente Southern California does not restrict usage based on early adherence.

Hwang et al considered any Kaiser Permanente member with any CPAP usage during the 12 months after being issued a device an active user. They tracked mean nightly minutes of use and the percentage of nights with ≥ 2 and ≥ 4 hours of average use.

Overall, 49% would have met the CMS criteria and used the therapy ≥ 4 hours on average each night for 70% of nights during the first 90 days. Kaiser Permanente members aged ≥ 65 years were more compliant, with 54% meeting the CMS benchmarks. ATS guidelines recognize that even ≥ 2 hours of CPAP per night on average can confer some benefits.

The average age in the study was 55 years, and the mean apnea-hypopnea index was 32-33 events per hour, suggesting severe obstructive sleep apnea at baseline. The cohort was diverse, with 42% White, 35% Hispanic, 10% Black, 9% Asian, and 4% other race or ethnicity.

Key Findings

A total of 64,568 adults would have been CMS adherent at 90 days; investigators compared outcomes at 12 months with another 67,867 nonadherent adults.

There were some significant differences between groups. The mean age was 56.4 years vs 53.7 years in the adherent group vs the nonadherent group; men made up a greater proportion of the adherent group, 68.5% vs 62.6%; and the mean number of events per hour was 35 vs 30 (P < .001 for all).

Among the 90-day nonadherent group, about 21% met the 2-hour or greater adherence benchmark, and approximately 14% used CPAP an average of ≥ 4 hours.

“Still a substantial number of [non-CMS adherent] patients are using CPAP,” Hwang said.

Failure to meet CMS adherence was associated with younger age, female sex, non-White race or ethnicity, lower socioeconomic status, and lower severity of obstructive sleep apnea.

“There is also an equity dimension. Whites had better adherence rates during the first 90 days, so there is already a disparity here in terms of outcomes,” Hwang said. Policy changes could improve access to long-term therapy on a more equitable basis, he added. For example, a 2023 ATS policy statement calls for a more patient-centric approach and a focus on reducing inequities.

An Arbitrary Requirement

The 90-day requirement seems a little short, said session co-moderator Oren Cohen, MD, assistant professor in the Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine at Icahn School of Medicine at Mount Sinai in New York City, when asked to comment. “It can take longer to get a patient back into the clinic and go through a lot of the trial and error that it takes to do a mask fitting and adjust the pressures.”

If a patient is using their CPAP device for fewer than 4 hours a night in the early period, it doesn’t mean things are failing, Cohen said. “It’s just that you’ve got to keep trying and pushing forward.”

Nonetheless, there are some long-term noncompliant patients, Cohen said. “I certainly don’t think that somebody who’s not using the device for years should continue to hold on to it. That resource can be reallocated to somebody who would get more benefit from it. But I think setting a 90-day and 4-hour rule seems arbitrary…and there should be more leeway there.”

The study was independently supported.

Hwang and Cohen reported having no relevant financial disclosures.

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

ORLANDO, Fla. — The Centers for Medicare & Medicaid Services (CMS) will not cover continuous positive airway pressure (CPAP) treatment for people who are nonadherent by 90 days. However, that requirement is too stringent, said researchers who found more than one third of adults who struggled with adherence initially still used the therapy 1 year later at levels associated with clinical benefit.

To test the requirement, investigators assessed 132,492 patients in the Kaiser Permanente Southern California system. The patients were issued CPAP devices to treat obstructive sleep apnea from 2015 to 2023. At 1 year, 36% who would have failed the CMS requirement were still using their CPAP.

The results counter CMS’ assumption that poor early CPAP use always leads to long-term abandonment, said Dennis Hwang, MD, co-chair of Sleep Medicine and medical director of the Sleep Disorders Center at Kaiser Permanente Southern California in Fontana, California.

"We should transition away from a one-size-fits-all definition of success," Hwang added at the American Thoracic Society (ATS) 2026 International Conference.

Background and Methodology

The 90-day adherence requirement does not only apply to Medicare or Medicaid recipients, Hwang said; many private insurers have adopted the same policy. In contrast, Kaiser Permanente Southern California does not restrict usage based on early adherence.

Hwang et al considered any Kaiser Permanente member with any CPAP usage during the 12 months after being issued a device an active user. They tracked mean nightly minutes of use and the percentage of nights with ≥ 2 and ≥ 4 hours of average use.

Overall, 49% would have met the CMS criteria and used the therapy ≥ 4 hours on average each night for 70% of nights during the first 90 days. Kaiser Permanente members aged ≥ 65 years were more compliant, with 54% meeting the CMS benchmarks. ATS guidelines recognize that even ≥ 2 hours of CPAP per night on average can confer some benefits.

The average age in the study was 55 years, and the mean apnea-hypopnea index was 32-33 events per hour, suggesting severe obstructive sleep apnea at baseline. The cohort was diverse, with 42% White, 35% Hispanic, 10% Black, 9% Asian, and 4% other race or ethnicity.

Key Findings

A total of 64,568 adults would have been CMS adherent at 90 days; investigators compared outcomes at 12 months with another 67,867 nonadherent adults.

There were some significant differences between groups. The mean age was 56.4 years vs 53.7 years in the adherent group vs the nonadherent group; men made up a greater proportion of the adherent group, 68.5% vs 62.6%; and the mean number of events per hour was 35 vs 30 (P < .001 for all).

Among the 90-day nonadherent group, about 21% met the 2-hour or greater adherence benchmark, and approximately 14% used CPAP an average of ≥ 4 hours.

“Still a substantial number of [non-CMS adherent] patients are using CPAP,” Hwang said.

Failure to meet CMS adherence was associated with younger age, female sex, non-White race or ethnicity, lower socioeconomic status, and lower severity of obstructive sleep apnea.

“There is also an equity dimension. Whites had better adherence rates during the first 90 days, so there is already a disparity here in terms of outcomes,” Hwang said. Policy changes could improve access to long-term therapy on a more equitable basis, he added. For example, a 2023 ATS policy statement calls for a more patient-centric approach and a focus on reducing inequities.

An Arbitrary Requirement

The 90-day requirement seems a little short, said session co-moderator Oren Cohen, MD, assistant professor in the Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine at Icahn School of Medicine at Mount Sinai in New York City, when asked to comment. “It can take longer to get a patient back into the clinic and go through a lot of the trial and error that it takes to do a mask fitting and adjust the pressures.”

If a patient is using their CPAP device for fewer than 4 hours a night in the early period, it doesn’t mean things are failing, Cohen said. “It’s just that you’ve got to keep trying and pushing forward.”

Nonetheless, there are some long-term noncompliant patients, Cohen said. “I certainly don’t think that somebody who’s not using the device for years should continue to hold on to it. That resource can be reallocated to somebody who would get more benefit from it. But I think setting a 90-day and 4-hour rule seems arbitrary…and there should be more leeway there.”

The study was independently supported.

Hwang and Cohen reported having no relevant financial disclosures.

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