Building the health care system of the future requires the thoughtful development and integration of innovative technologies to positively transform care.^1-4 Extended reality (XR) represents a spectrum of emerging technologies that have the potential to enhance health care. This includes virtual reality (VR), where a computer-generated visual experience fills the screen; augmented reality (AR), which allows users to see computer-generated images superimposed into an otherwise normal real-world field of view; and mixed reality (MR), which allows users to interact and manipulate computer-generated AR images.

Clinicians and researchers have begun exploring the potential of XR to address a wide variety of health care challenges. A recent systematic review concluded that many clinical studies in this area have small sample sizes and are in the preclinical, proof-of-concept stage, but demonstrate the potential and impact of the underlying VR, AR, and MR technologies.⁵ Common emerging health care uses for XR include medical education, training, presurgical planning, surgical guidance, distraction therapy for pain and anxiety, and home health indications, including rehabilitation.^5-39

Methods

The VA Palo Alto Health Care System (VAPAHCS) consists of 3 inpatient hospitals and 7 outpatient clinics, provides a full range of care services to > 90,000 enrolled veterans with 800 hospital beds, 3 nursing homes, and a 100-bed domiciliary. The facility also runs data-driven care projects in research, innovation, and evidence-based practice group under nursing services.⁴⁸ This project was performed by the VA National Center for Collaborative Healthcare Innovation at the VAPAHCS campus.

The combined technical system used for this assessment included a wireless communication network, AR/MR hardware, and software. Medivis AnatomyX software displayed an interactive human anatomy atlas segmented into about 6000 individual interactive parts. Medivis SurgicalAR received US Food and Drug Administration clearance for presurgical planning and was used to transform and display deidentified diagnostic images (eg, magnetic resonance images and computed tomography) in 3-dimensional (3D) interactive holograms (Figures 1 and 2).

 The wireless Microsoft HoloLens 2 AR/MR headset was used for viewing and sensor-enabled collaborative interaction. Multiple participants in the same physical location simultaneously participated and interacted with 3D holograms. The interactive hologram data were enabled for 3D stereoscopic viewing and manipulation.

Setting and Participants

We reviewed published studies that used questionnaires to evaluate institutions’ level of innovation and new technology user acceptance to develop the questionnaire.^49-56 Questions and methods were modified, with a focus on understanding the impact on hospital employees. The questionnaire consisted of 2 predemonstration and 3 postdemonstration sections. The first section included background questions. The second (predemonstration) and third (postdemonstration) sections provided matched questions on feelings about the VA. The fourth section included 2 unmatched questions about how the participant felt this technology would impact veterans and whether the VA should implement similar technologies. We used a 5-point Likert scale for sections 2, 3 and 4 (1 = not at all to 5 = extremely). Two unmatched free-text questions asked how the technology could be used in the participant’s hospital service, and another open-ended question asked for any additional comments. To reduce potential reporting bias, 2 VA employees that did not work at VAPAHCS assisted with the survey distribution and collection. VAPAHCS staff were informed by all employee email and facility intranet of the opportunity to participate; the voluntary demonstration and survey took place on February 10 and 11, 2020.

Data Analysis

All matching pre/post questions were analyzed together to determine statistically significant differences using the Wilcoxon signed rank matched pairs test and pooled t test. Survey respondents were also grouped by employment type to evaluate the impact on subgroups. Results were also grouped by VA tenure into 4 categorical 10-year increments (0-10, 11-20, 21-30, 31-40). Additionally, analysis of variance (ANOVA) was performed on employment types and VA tenure to understand whether there was a statistically significant difference in responses by these subgroups. Respondents’ optional free-text answers were manually reviewed by 2 authors (ZPV and DMA), classified, coded by the common themes, and analyzed for comparison.

Results

A total of 166 participants completed the predemonstration survey, which was a requirement for participating in the AR demonstration. Of those, 159 staff members (95.8%) also completed at least part of the postdemonstration paired structured questions, and their results were included in the analysis.

Paired Questions

For questions about how innovative the VA is, 108 of 152 participants (71.1%) provided higher scores after the demonstration, 42 (27.6%) had no change, and 2 (1.3%) provided decreased scores. The mean innovative score increased from 3.4 predemonstration to 4.5 postdemonstration on a Likert scale, which is a 1.1 point increase from predemonstration to postdemonstration (95% CI, 0.9- 1.2) or a 22% increase (95% CI, 18%-24%) (P < .001). Respondents level of excitement about VA also increased with 82 of 157 participants (52.2%) providing higher scores after the demonstration, 71 (45.2%) had no change, and 4 scores (2.5%) decreased. The predemonstration mean excitement score of 3.7 increased to 4.3 postdemonstration, which is a 0.6 point increase from before to after the demonstration (95% CI, 0.5-0.7) or a 12% increase (95% CI, 10%-14%) (P < .001). In the survey, 36 of 149 participants (24.2%) had higher scores for their expectation to continue working at VA postdemonstration, 109 (73.2%) had no change, and 4 scores (2.7%) decreased. The mean employee retention score increased from 4.2 predemonstration to 4.5 postdemonstration, which is a 0.3 point increase between pre/post (95% CI, 0.2-0.4) or a 6% increase (95% CI, 4%-8%) (P < .001)

The pre/post questions were analyzed using 1-way ANOVA by hospital department and VA tenure. The responses by department were not statistically significant. Of the 159 employees assessed, 101 respondents (63.5%) had 0 to 10 years VA tenure, 44 (27.7%) had 11 to 20 years, 10 (6.3%) had 21 to 30 years, and 4 (2.5%) had > 31 to 40 years. Length of VA tenure did not impact respondent excitement. Respondents opinions on innovation in the 0 to 10 year and the 11 to 20 year groups rose from 3.2 and 3.7 predemonstration to 4.3 and 4.6 postdemonstration, respectively (P < .001 for both statistical comparisons) (Table 2). Interestingly, the 0 to 10 group saw a 9% rise from a 4.0 score predemonstration to a 4.4 score postdemonstration (P < .001), indicating that the demonstration had a positive impact on their plans to continue employment at VA (Table 3).

Sex did not play a significant role in how respondents answered questions regarding VA excitement or innovation. However, there was a statistically significant difference in how male and female respondents answered the predemonstration question about their plans to continue VA employment, according to the Wilcoxon rank sum test. Predemonstration, female respondents had a mean score of 4.1, which was 6% lower than the 4.4 score of male colleagues (P = .04). Veteran status did have an impact on how respondents felt about VA innovation, and their plans to continue employment at VA. After the demonstration, veteran staff felt the VA was more innovative compared with nonveterans: 4.7 vs 4.4, respectively, a 6% difference (P = .02) Similarly, for the continued VA employment question, veterans had a mean score of 4.8 vs 4.4 for nonveterans, an 8% difference (P = .03) These results suggest that the demonstration had more of an impact on veteran employees vs nonveteran employees.

Unpaired Questions

There were 2 structured unpaired postdemonstration questions. Respondents agreed that similar technology would impact veteran health care with mean (SD) of 4.6 (0.6) and a median score of 5 on a 5-point Likert scale. Respondents also agreed on the importance of implementing similar innovations with mean (SD) of 4.7 (0.5), and a median score of 5.

The survey asked how this technology could benefit their hospital service department and had 64 responses. Forty-six respondents saw applications for education or patient care/surgery. Other responses shared excitement about the technology and its potential to positively impact patient education. There were 37 responses to the open-ended question: 21 respondents expressed excitement for the technology, and 10 respondents reiterated that the demonstration would be of benefit to patient care/surgery and training.

Discussion

Successful development, design, and deployment of any new health care tool depends on leveraging insights from the employees that will be using and supporting these systems. Correspondingly, understanding the impact that advanced technologies have on health care employees’ satisfaction, morale, and retention is critical to our overall institutional strategy. Our findings show that a one-time experience with AR/MR technology elicited positive employee reactions. Of note, the survey revealed statistically significant improvements in staff’s view of the VA, with the greatest positive impact for questions about innovation, followed by excitement to work at the VA, and likelihood to continue work at the VA. It is very disruptive and costly when health care employees leave, and improving employee satisfaction and morale is important for better patient care and patient satisfaction, which is priority for VAPAHCS leadership.^57-62

The paired predemonstration and postdemonstration scores were similarly high, nearing the top threshold available for the Likert scale (4.3 to 4.5). Furthermore, the least incremental improvement for these responses was observed for topics that had the highest initial baseline score. Therefore, the improvements observed for the paired questions may have more to do with the high baseline values.

Of additional interest, the self-reported likelihood of continuing to work at the VA increased the most for female employees, veteran employees, and employees with the least number of years at the VA. These demographic differences have important implications for VA staff recruitment and retention strategies.⁶² The unpaired questions about the impact on veteran care and whether the VA should continue similar work demonstrated extremely high support with median scores of 5 for both questions. The free-text postdemonstration responses also demonstrate similar positive themes, with a disposition for excitement about both the training and patient care applications for this technology. In addition, respondents felt strongly that this and other similar technologies will positively impact the health care for veterans and that the VA should continue these efforts.

Strengths and Limitations

A strength of this assessment is the ability to evaluate survey responses that were systematically collected and matched from the same individual immediately before and after exposure to the new technology. The free-text responses provided additional important information that both confirmed the results and provided additional valued supplementary guidance for future implementation strategies, which is critical for our translational implementation goals. An additional strength is that the voluntary surveys were managed by non-VAPAHCS colleagues, limiting potential bias. Importantly, the number of respondents allowed a statistically significant assessment of important health care employee metrics. These results have emphasized how being part of an innovative organization, and the introduction of advanced AR/MR technology, improve employees’ satisfaction and morale about where they work as well as their intention to stay at their institution.

A limitation of this assessment was the lack of comparative data for employee acceptance of other technologies at VAPAHCS. This limits our ability to differentiate whether the strong positive results observed in this evaluation were a result of the specific technology assessed, or of new and advanced health care technology in general. Nonetheless, our unpaired questions, which received extremely high scores, also included participant questions about comparing the system with other similar technologies. This assessment was also focused on veteran care, which limits generalizability.

Conclusions

One-time exposure to advanced AR technology for health care significantly increased employee morale as measured by excitement about working at the VA as well as employee intention to continue employment at the VA. These collateral benefits of the technology are particularly important in health care because our employees are our most important asset and improving employee morale equates to better patient care. Positive impacts were most pronounced for women employees, newer VA employees, and employees who are also veterans. These more detailed insights are also positioned to have a direct impact on employee recruitment and retention strategies. Additional valuable insights regarding the most applicable use of the technology in the clinical setting were also obtained. 

Acknowledgments

We thank Andrew Spiegelman, Hyewon Kim, Jonathan Sills, and Alexander Erickson for their assistance in developing the survey questions. We also thank Jason Rhodes and Mark Bulson for traveling to our facility to assist with managing the anonymous surveys during the demonstration event.

Building the health care system of the future requires the thoughtful development and integration of innovative technologies to positively transform care.^1-4 Extended reality (XR) represents a spectrum of emerging technologies that have the potential to enhance health care. This includes virtual reality (VR), where a computer-generated visual experience fills the screen; augmented reality (AR), which allows users to see computer-generated images superimposed into an otherwise normal real-world field of view; and mixed reality (MR), which allows users to interact and manipulate computer-generated AR images.

Clinicians and researchers have begun exploring the potential of XR to address a wide variety of health care challenges. A recent systematic review concluded that many clinical studies in this area have small sample sizes and are in the preclinical, proof-of-concept stage, but demonstrate the potential and impact of the underlying VR, AR, and MR technologies.⁵ Common emerging health care uses for XR include medical education, training, presurgical planning, surgical guidance, distraction therapy for pain and anxiety, and home health indications, including rehabilitation.^5-39

Methods

The VA Palo Alto Health Care System (VAPAHCS) consists of 3 inpatient hospitals and 7 outpatient clinics, provides a full range of care services to > 90,000 enrolled veterans with 800 hospital beds, 3 nursing homes, and a 100-bed domiciliary. The facility also runs data-driven care projects in research, innovation, and evidence-based practice group under nursing services.⁴⁸ This project was performed by the VA National Center for Collaborative Healthcare Innovation at the VAPAHCS campus.

The combined technical system used for this assessment included a wireless communication network, AR/MR hardware, and software. Medivis AnatomyX software displayed an interactive human anatomy atlas segmented into about 6000 individual interactive parts. Medivis SurgicalAR received US Food and Drug Administration clearance for presurgical planning and was used to transform and display deidentified diagnostic images (eg, magnetic resonance images and computed tomography) in 3-dimensional (3D) interactive holograms (Figures 1 and 2).

 The wireless Microsoft HoloLens 2 AR/MR headset was used for viewing and sensor-enabled collaborative interaction. Multiple participants in the same physical location simultaneously participated and interacted with 3D holograms. The interactive hologram data were enabled for 3D stereoscopic viewing and manipulation.

Setting and Participants

We reviewed published studies that used questionnaires to evaluate institutions’ level of innovation and new technology user acceptance to develop the questionnaire.^49-56 Questions and methods were modified, with a focus on understanding the impact on hospital employees. The questionnaire consisted of 2 predemonstration and 3 postdemonstration sections. The first section included background questions. The second (predemonstration) and third (postdemonstration) sections provided matched questions on feelings about the VA. The fourth section included 2 unmatched questions about how the participant felt this technology would impact veterans and whether the VA should implement similar technologies. We used a 5-point Likert scale for sections 2, 3 and 4 (1 = not at all to 5 = extremely). Two unmatched free-text questions asked how the technology could be used in the participant’s hospital service, and another open-ended question asked for any additional comments. To reduce potential reporting bias, 2 VA employees that did not work at VAPAHCS assisted with the survey distribution and collection. VAPAHCS staff were informed by all employee email and facility intranet of the opportunity to participate; the voluntary demonstration and survey took place on February 10 and 11, 2020.

Data Analysis

All matching pre/post questions were analyzed together to determine statistically significant differences using the Wilcoxon signed rank matched pairs test and pooled t test. Survey respondents were also grouped by employment type to evaluate the impact on subgroups. Results were also grouped by VA tenure into 4 categorical 10-year increments (0-10, 11-20, 21-30, 31-40). Additionally, analysis of variance (ANOVA) was performed on employment types and VA tenure to understand whether there was a statistically significant difference in responses by these subgroups. Respondents’ optional free-text answers were manually reviewed by 2 authors (ZPV and DMA), classified, coded by the common themes, and analyzed for comparison.

Results

A total of 166 participants completed the predemonstration survey, which was a requirement for participating in the AR demonstration. Of those, 159 staff members (95.8%) also completed at least part of the postdemonstration paired structured questions, and their results were included in the analysis.

Paired Questions

For questions about how innovative the VA is, 108 of 152 participants (71.1%) provided higher scores after the demonstration, 42 (27.6%) had no change, and 2 (1.3%) provided decreased scores. The mean innovative score increased from 3.4 predemonstration to 4.5 postdemonstration on a Likert scale, which is a 1.1 point increase from predemonstration to postdemonstration (95% CI, 0.9- 1.2) or a 22% increase (95% CI, 18%-24%) (P < .001). Respondents level of excitement about VA also increased with 82 of 157 participants (52.2%) providing higher scores after the demonstration, 71 (45.2%) had no change, and 4 scores (2.5%) decreased. The predemonstration mean excitement score of 3.7 increased to 4.3 postdemonstration, which is a 0.6 point increase from before to after the demonstration (95% CI, 0.5-0.7) or a 12% increase (95% CI, 10%-14%) (P < .001). In the survey, 36 of 149 participants (24.2%) had higher scores for their expectation to continue working at VA postdemonstration, 109 (73.2%) had no change, and 4 scores (2.7%) decreased. The mean employee retention score increased from 4.2 predemonstration to 4.5 postdemonstration, which is a 0.3 point increase between pre/post (95% CI, 0.2-0.4) or a 6% increase (95% CI, 4%-8%) (P < .001)

The pre/post questions were analyzed using 1-way ANOVA by hospital department and VA tenure. The responses by department were not statistically significant. Of the 159 employees assessed, 101 respondents (63.5%) had 0 to 10 years VA tenure, 44 (27.7%) had 11 to 20 years, 10 (6.3%) had 21 to 30 years, and 4 (2.5%) had > 31 to 40 years. Length of VA tenure did not impact respondent excitement. Respondents opinions on innovation in the 0 to 10 year and the 11 to 20 year groups rose from 3.2 and 3.7 predemonstration to 4.3 and 4.6 postdemonstration, respectively (P < .001 for both statistical comparisons) (Table 2). Interestingly, the 0 to 10 group saw a 9% rise from a 4.0 score predemonstration to a 4.4 score postdemonstration (P < .001), indicating that the demonstration had a positive impact on their plans to continue employment at VA (Table 3).

Sex did not play a significant role in how respondents answered questions regarding VA excitement or innovation. However, there was a statistically significant difference in how male and female respondents answered the predemonstration question about their plans to continue VA employment, according to the Wilcoxon rank sum test. Predemonstration, female respondents had a mean score of 4.1, which was 6% lower than the 4.4 score of male colleagues (P = .04). Veteran status did have an impact on how respondents felt about VA innovation, and their plans to continue employment at VA. After the demonstration, veteran staff felt the VA was more innovative compared with nonveterans: 4.7 vs 4.4, respectively, a 6% difference (P = .02) Similarly, for the continued VA employment question, veterans had a mean score of 4.8 vs 4.4 for nonveterans, an 8% difference (P = .03) These results suggest that the demonstration had more of an impact on veteran employees vs nonveteran employees.

Unpaired Questions

There were 2 structured unpaired postdemonstration questions. Respondents agreed that similar technology would impact veteran health care with mean (SD) of 4.6 (0.6) and a median score of 5 on a 5-point Likert scale. Respondents also agreed on the importance of implementing similar innovations with mean (SD) of 4.7 (0.5), and a median score of 5.

The survey asked how this technology could benefit their hospital service department and had 64 responses. Forty-six respondents saw applications for education or patient care/surgery. Other responses shared excitement about the technology and its potential to positively impact patient education. There were 37 responses to the open-ended question: 21 respondents expressed excitement for the technology, and 10 respondents reiterated that the demonstration would be of benefit to patient care/surgery and training.

Discussion

Successful development, design, and deployment of any new health care tool depends on leveraging insights from the employees that will be using and supporting these systems. Correspondingly, understanding the impact that advanced technologies have on health care employees’ satisfaction, morale, and retention is critical to our overall institutional strategy. Our findings show that a one-time experience with AR/MR technology elicited positive employee reactions. Of note, the survey revealed statistically significant improvements in staff’s view of the VA, with the greatest positive impact for questions about innovation, followed by excitement to work at the VA, and likelihood to continue work at the VA. It is very disruptive and costly when health care employees leave, and improving employee satisfaction and morale is important for better patient care and patient satisfaction, which is priority for VAPAHCS leadership.^57-62

The paired predemonstration and postdemonstration scores were similarly high, nearing the top threshold available for the Likert scale (4.3 to 4.5). Furthermore, the least incremental improvement for these responses was observed for topics that had the highest initial baseline score. Therefore, the improvements observed for the paired questions may have more to do with the high baseline values.

Of additional interest, the self-reported likelihood of continuing to work at the VA increased the most for female employees, veteran employees, and employees with the least number of years at the VA. These demographic differences have important implications for VA staff recruitment and retention strategies.⁶² The unpaired questions about the impact on veteran care and whether the VA should continue similar work demonstrated extremely high support with median scores of 5 for both questions. The free-text postdemonstration responses also demonstrate similar positive themes, with a disposition for excitement about both the training and patient care applications for this technology. In addition, respondents felt strongly that this and other similar technologies will positively impact the health care for veterans and that the VA should continue these efforts.

Strengths and Limitations

A strength of this assessment is the ability to evaluate survey responses that were systematically collected and matched from the same individual immediately before and after exposure to the new technology. The free-text responses provided additional important information that both confirmed the results and provided additional valued supplementary guidance for future implementation strategies, which is critical for our translational implementation goals. An additional strength is that the voluntary surveys were managed by non-VAPAHCS colleagues, limiting potential bias. Importantly, the number of respondents allowed a statistically significant assessment of important health care employee metrics. These results have emphasized how being part of an innovative organization, and the introduction of advanced AR/MR technology, improve employees’ satisfaction and morale about where they work as well as their intention to stay at their institution.

A limitation of this assessment was the lack of comparative data for employee acceptance of other technologies at VAPAHCS. This limits our ability to differentiate whether the strong positive results observed in this evaluation were a result of the specific technology assessed, or of new and advanced health care technology in general. Nonetheless, our unpaired questions, which received extremely high scores, also included participant questions about comparing the system with other similar technologies. This assessment was also focused on veteran care, which limits generalizability.

Conclusions

One-time exposure to advanced AR technology for health care significantly increased employee morale as measured by excitement about working at the VA as well as employee intention to continue employment at the VA. These collateral benefits of the technology are particularly important in health care because our employees are our most important asset and improving employee morale equates to better patient care. Positive impacts were most pronounced for women employees, newer VA employees, and employees who are also veterans. These more detailed insights are also positioned to have a direct impact on employee recruitment and retention strategies. Additional valuable insights regarding the most applicable use of the technology in the clinical setting were also obtained. 

Acknowledgments

We thank Andrew Spiegelman, Hyewon Kim, Jonathan Sills, and Alexander Erickson for their assistance in developing the survey questions. We also thank Jason Rhodes and Mark Bulson for traveling to our facility to assist with managing the anonymous surveys during the demonstration event.

Building the health care system of the future requires the thoughtful development and integration of innovative technologies to positively transform care.^1-4 Extended reality (XR) represents a spectrum of emerging technologies that have the potential to enhance health care. This includes virtual reality (VR), where a computer-generated visual experience fills the screen; augmented reality (AR), which allows users to see computer-generated images superimposed into an otherwise normal real-world field of view; and mixed reality (MR), which allows users to interact and manipulate computer-generated AR images.

Clinicians and researchers have begun exploring the potential of XR to address a wide variety of health care challenges. A recent systematic review concluded that many clinical studies in this area have small sample sizes and are in the preclinical, proof-of-concept stage, but demonstrate the potential and impact of the underlying VR, AR, and MR technologies.⁵ Common emerging health care uses for XR include medical education, training, presurgical planning, surgical guidance, distraction therapy for pain and anxiety, and home health indications, including rehabilitation.^5-39

Methods

The VA Palo Alto Health Care System (VAPAHCS) consists of 3 inpatient hospitals and 7 outpatient clinics, provides a full range of care services to > 90,000 enrolled veterans with 800 hospital beds, 3 nursing homes, and a 100-bed domiciliary. The facility also runs data-driven care projects in research, innovation, and evidence-based practice group under nursing services.⁴⁸ This project was performed by the VA National Center for Collaborative Healthcare Innovation at the VAPAHCS campus.

The combined technical system used for this assessment included a wireless communication network, AR/MR hardware, and software. Medivis AnatomyX software displayed an interactive human anatomy atlas segmented into about 6000 individual interactive parts. Medivis SurgicalAR received US Food and Drug Administration clearance for presurgical planning and was used to transform and display deidentified diagnostic images (eg, magnetic resonance images and computed tomography) in 3-dimensional (3D) interactive holograms (Figures 1 and 2).

 The wireless Microsoft HoloLens 2 AR/MR headset was used for viewing and sensor-enabled collaborative interaction. Multiple participants in the same physical location simultaneously participated and interacted with 3D holograms. The interactive hologram data were enabled for 3D stereoscopic viewing and manipulation.

Setting and Participants

We reviewed published studies that used questionnaires to evaluate institutions’ level of innovation and new technology user acceptance to develop the questionnaire.^49-56 Questions and methods were modified, with a focus on understanding the impact on hospital employees. The questionnaire consisted of 2 predemonstration and 3 postdemonstration sections. The first section included background questions. The second (predemonstration) and third (postdemonstration) sections provided matched questions on feelings about the VA. The fourth section included 2 unmatched questions about how the participant felt this technology would impact veterans and whether the VA should implement similar technologies. We used a 5-point Likert scale for sections 2, 3 and 4 (1 = not at all to 5 = extremely). Two unmatched free-text questions asked how the technology could be used in the participant’s hospital service, and another open-ended question asked for any additional comments. To reduce potential reporting bias, 2 VA employees that did not work at VAPAHCS assisted with the survey distribution and collection. VAPAHCS staff were informed by all employee email and facility intranet of the opportunity to participate; the voluntary demonstration and survey took place on February 10 and 11, 2020.

Data Analysis

All matching pre/post questions were analyzed together to determine statistically significant differences using the Wilcoxon signed rank matched pairs test and pooled t test. Survey respondents were also grouped by employment type to evaluate the impact on subgroups. Results were also grouped by VA tenure into 4 categorical 10-year increments (0-10, 11-20, 21-30, 31-40). Additionally, analysis of variance (ANOVA) was performed on employment types and VA tenure to understand whether there was a statistically significant difference in responses by these subgroups. Respondents’ optional free-text answers were manually reviewed by 2 authors (ZPV and DMA), classified, coded by the common themes, and analyzed for comparison.

Results

A total of 166 participants completed the predemonstration survey, which was a requirement for participating in the AR demonstration. Of those, 159 staff members (95.8%) also completed at least part of the postdemonstration paired structured questions, and their results were included in the analysis.

Paired Questions

For questions about how innovative the VA is, 108 of 152 participants (71.1%) provided higher scores after the demonstration, 42 (27.6%) had no change, and 2 (1.3%) provided decreased scores. The mean innovative score increased from 3.4 predemonstration to 4.5 postdemonstration on a Likert scale, which is a 1.1 point increase from predemonstration to postdemonstration (95% CI, 0.9- 1.2) or a 22% increase (95% CI, 18%-24%) (P < .001). Respondents level of excitement about VA also increased with 82 of 157 participants (52.2%) providing higher scores after the demonstration, 71 (45.2%) had no change, and 4 scores (2.5%) decreased. The predemonstration mean excitement score of 3.7 increased to 4.3 postdemonstration, which is a 0.6 point increase from before to after the demonstration (95% CI, 0.5-0.7) or a 12% increase (95% CI, 10%-14%) (P < .001). In the survey, 36 of 149 participants (24.2%) had higher scores for their expectation to continue working at VA postdemonstration, 109 (73.2%) had no change, and 4 scores (2.7%) decreased. The mean employee retention score increased from 4.2 predemonstration to 4.5 postdemonstration, which is a 0.3 point increase between pre/post (95% CI, 0.2-0.4) or a 6% increase (95% CI, 4%-8%) (P < .001)

The pre/post questions were analyzed using 1-way ANOVA by hospital department and VA tenure. The responses by department were not statistically significant. Of the 159 employees assessed, 101 respondents (63.5%) had 0 to 10 years VA tenure, 44 (27.7%) had 11 to 20 years, 10 (6.3%) had 21 to 30 years, and 4 (2.5%) had > 31 to 40 years. Length of VA tenure did not impact respondent excitement. Respondents opinions on innovation in the 0 to 10 year and the 11 to 20 year groups rose from 3.2 and 3.7 predemonstration to 4.3 and 4.6 postdemonstration, respectively (P < .001 for both statistical comparisons) (Table 2). Interestingly, the 0 to 10 group saw a 9% rise from a 4.0 score predemonstration to a 4.4 score postdemonstration (P < .001), indicating that the demonstration had a positive impact on their plans to continue employment at VA (Table 3).

Sex did not play a significant role in how respondents answered questions regarding VA excitement or innovation. However, there was a statistically significant difference in how male and female respondents answered the predemonstration question about their plans to continue VA employment, according to the Wilcoxon rank sum test. Predemonstration, female respondents had a mean score of 4.1, which was 6% lower than the 4.4 score of male colleagues (P = .04). Veteran status did have an impact on how respondents felt about VA innovation, and their plans to continue employment at VA. After the demonstration, veteran staff felt the VA was more innovative compared with nonveterans: 4.7 vs 4.4, respectively, a 6% difference (P = .02) Similarly, for the continued VA employment question, veterans had a mean score of 4.8 vs 4.4 for nonveterans, an 8% difference (P = .03) These results suggest that the demonstration had more of an impact on veteran employees vs nonveteran employees.

Unpaired Questions

There were 2 structured unpaired postdemonstration questions. Respondents agreed that similar technology would impact veteran health care with mean (SD) of 4.6 (0.6) and a median score of 5 on a 5-point Likert scale. Respondents also agreed on the importance of implementing similar innovations with mean (SD) of 4.7 (0.5), and a median score of 5.

The survey asked how this technology could benefit their hospital service department and had 64 responses. Forty-six respondents saw applications for education or patient care/surgery. Other responses shared excitement about the technology and its potential to positively impact patient education. There were 37 responses to the open-ended question: 21 respondents expressed excitement for the technology, and 10 respondents reiterated that the demonstration would be of benefit to patient care/surgery and training.

Discussion

Successful development, design, and deployment of any new health care tool depends on leveraging insights from the employees that will be using and supporting these systems. Correspondingly, understanding the impact that advanced technologies have on health care employees’ satisfaction, morale, and retention is critical to our overall institutional strategy. Our findings show that a one-time experience with AR/MR technology elicited positive employee reactions. Of note, the survey revealed statistically significant improvements in staff’s view of the VA, with the greatest positive impact for questions about innovation, followed by excitement to work at the VA, and likelihood to continue work at the VA. It is very disruptive and costly when health care employees leave, and improving employee satisfaction and morale is important for better patient care and patient satisfaction, which is priority for VAPAHCS leadership.^57-62

The paired predemonstration and postdemonstration scores were similarly high, nearing the top threshold available for the Likert scale (4.3 to 4.5). Furthermore, the least incremental improvement for these responses was observed for topics that had the highest initial baseline score. Therefore, the improvements observed for the paired questions may have more to do with the high baseline values.

Of additional interest, the self-reported likelihood of continuing to work at the VA increased the most for female employees, veteran employees, and employees with the least number of years at the VA. These demographic differences have important implications for VA staff recruitment and retention strategies.⁶² The unpaired questions about the impact on veteran care and whether the VA should continue similar work demonstrated extremely high support with median scores of 5 for both questions. The free-text postdemonstration responses also demonstrate similar positive themes, with a disposition for excitement about both the training and patient care applications for this technology. In addition, respondents felt strongly that this and other similar technologies will positively impact the health care for veterans and that the VA should continue these efforts.

Strengths and Limitations

A strength of this assessment is the ability to evaluate survey responses that were systematically collected and matched from the same individual immediately before and after exposure to the new technology. The free-text responses provided additional important information that both confirmed the results and provided additional valued supplementary guidance for future implementation strategies, which is critical for our translational implementation goals. An additional strength is that the voluntary surveys were managed by non-VAPAHCS colleagues, limiting potential bias. Importantly, the number of respondents allowed a statistically significant assessment of important health care employee metrics. These results have emphasized how being part of an innovative organization, and the introduction of advanced AR/MR technology, improve employees’ satisfaction and morale about where they work as well as their intention to stay at their institution.

A limitation of this assessment was the lack of comparative data for employee acceptance of other technologies at VAPAHCS. This limits our ability to differentiate whether the strong positive results observed in this evaluation were a result of the specific technology assessed, or of new and advanced health care technology in general. Nonetheless, our unpaired questions, which received extremely high scores, also included participant questions about comparing the system with other similar technologies. This assessment was also focused on veteran care, which limits generalizability.

Conclusions

One-time exposure to advanced AR technology for health care significantly increased employee morale as measured by excitement about working at the VA as well as employee intention to continue employment at the VA. These collateral benefits of the technology are particularly important in health care because our employees are our most important asset and improving employee morale equates to better patient care. Positive impacts were most pronounced for women employees, newer VA employees, and employees who are also veterans. These more detailed insights are also positioned to have a direct impact on employee recruitment and retention strategies. Additional valuable insights regarding the most applicable use of the technology in the clinical setting were also obtained. 

Acknowledgments

We thank Andrew Spiegelman, Hyewon Kim, Jonathan Sills, and Alexander Erickson for their assistance in developing the survey questions. We also thank Jason Rhodes and Mark Bulson for traveling to our facility to assist with managing the anonymous surveys during the demonstration event.

Researchers have identified a novel mutation in a patient with microvillus inclusion disease (MVID) and rapidly developed a specific mouse model to find insights into the disease process.

MVID is characterized by severe diarrhea, generally beginning within a few hours of birth. The condition is caused by inactivating mutations in the gene myosin VB (MYO5B). Affected individuals usually require lifetime use of total parenteral nutrition or small-bowel transplantation.

More than 100 MYO5B mutations have been identified in MVID patients, most of whom inherit two unique mutant alleles. This can lead to variability in phenotypes, which single-mutation animal models have been unable to mimic. Generally, patients have atrophy of microvilli on enterocytes as well as inclusion bodies within enterocytes that contain microvilli.

In the study, published in Cellular and Molecular Gastroenterology and Hepatology, researchers describe genetic sequencing of MYO5B mutations in a patient and both parents. One mutation is predicted to lead to protein truncation (c.1821delG), and the other (c.1555G>A) appeared to be inherited from the patient’s mother. The patient suffered from severe diarrhea after birth and was intermittently feeding intolerant.

The researchers conducted a range of diagnostic tests and biopsies. One particularly interesting finding was expression of the A-kinase anchoring protein 350 in the vicinity of the inclusion, wrote Andreanna Burman and her coauthors at Vanderbilt University, Nashville, Tenn. This protein takes part in a protein-mediating scaffolding pathway, suggesting that it could play a role in the development of the inclusions.

The researchers used multiplexed immunofluorescence (MxIF) staining of a biopsy of the duodenum to look for expression of a range of proteins. They found a striking decrease in enterocytes that express glucose transporter 2, implying that malabsorption might be due at least in part to enterocytes that fail to mature.

The patient also had internalization of apical nutrient transporters, which has been reported in other MVID patients. The researchers also developed a mouse model that incorporated the patient’s novel compound heterozygous genotype, which they cross-bred to produce a tamoxifen-inducible mouse model.

After the tamoxifen injection, the patient-mimicking animals exhibited a severe watery diarrhea, losing 19% of their body weight by day 4. The animals’ intestines showed a similar phenotype to that of the patient.

The apical sodium transporters sodium-glucose cotransporter 1 (SGLT1), apical sodium-dependent bile transporter, and NHE3 were internalized away from the apical membrane of the enterocytes in the patient-mimicking model animals. This structural difference may explain the limited absorption of sodium and water and the resultant watery diarrhea. The researchers also noted disruption of the actinin-4+ terminal web structure, as well as increased SGLT1 localization with lysosome-associated membrane protein 1+ lysosomes within the mouse model enterocytes. This association may indicate degradation of mislocalized proteins, the authors noted, which has also been seen in expanded RAB7+ vesicles within MVID patient tissues.

Other signs pointed to the expansion of immature cells in the upper crypt and lower villus, as well as faster shedding of enterocytes in the villus than in control animals. Scanning electron microscope images also showed immature and disorganized microvilli in the enterocytes of the patient-mimicking mice.

Taken together, “these findings are consistent with a deficit in enterocyte maturation in Myo5b(G519R) mice and in the patient with the MYO5B(G519R) mutation,” the authors wrote.

The authors suggest that their approach could be used more generally to quickly create mouse models of patient-specific monogenic congenital disorders.

The authors disclosed no conflicts of interest. The research was funded by the National Foundation of Science, National Institutes of Health, Vanderbilt Digestive Diseases Research Center Pilot and Feasibility grant, an American Physiological Society John F. Perkins, Jr. Research Career Enhancement Award, and a gift from the Christine Volpe Fund.

Researchers have identified a novel mutation in a patient with microvillus inclusion disease (MVID) and rapidly developed a specific mouse model to find insights into the disease process.

MVID is characterized by severe diarrhea, generally beginning within a few hours of birth. The condition is caused by inactivating mutations in the gene myosin VB (MYO5B). Affected individuals usually require lifetime use of total parenteral nutrition or small-bowel transplantation.

More than 100 MYO5B mutations have been identified in MVID patients, most of whom inherit two unique mutant alleles. This can lead to variability in phenotypes, which single-mutation animal models have been unable to mimic. Generally, patients have atrophy of microvilli on enterocytes as well as inclusion bodies within enterocytes that contain microvilli.

In the study, published in Cellular and Molecular Gastroenterology and Hepatology, researchers describe genetic sequencing of MYO5B mutations in a patient and both parents. One mutation is predicted to lead to protein truncation (c.1821delG), and the other (c.1555G>A) appeared to be inherited from the patient’s mother. The patient suffered from severe diarrhea after birth and was intermittently feeding intolerant.

The researchers conducted a range of diagnostic tests and biopsies. One particularly interesting finding was expression of the A-kinase anchoring protein 350 in the vicinity of the inclusion, wrote Andreanna Burman and her coauthors at Vanderbilt University, Nashville, Tenn. This protein takes part in a protein-mediating scaffolding pathway, suggesting that it could play a role in the development of the inclusions.

The researchers used multiplexed immunofluorescence (MxIF) staining of a biopsy of the duodenum to look for expression of a range of proteins. They found a striking decrease in enterocytes that express glucose transporter 2, implying that malabsorption might be due at least in part to enterocytes that fail to mature.

The patient also had internalization of apical nutrient transporters, which has been reported in other MVID patients. The researchers also developed a mouse model that incorporated the patient’s novel compound heterozygous genotype, which they cross-bred to produce a tamoxifen-inducible mouse model.

After the tamoxifen injection, the patient-mimicking animals exhibited a severe watery diarrhea, losing 19% of their body weight by day 4. The animals’ intestines showed a similar phenotype to that of the patient.

The apical sodium transporters sodium-glucose cotransporter 1 (SGLT1), apical sodium-dependent bile transporter, and NHE3 were internalized away from the apical membrane of the enterocytes in the patient-mimicking model animals. This structural difference may explain the limited absorption of sodium and water and the resultant watery diarrhea. The researchers also noted disruption of the actinin-4+ terminal web structure, as well as increased SGLT1 localization with lysosome-associated membrane protein 1+ lysosomes within the mouse model enterocytes. This association may indicate degradation of mislocalized proteins, the authors noted, which has also been seen in expanded RAB7+ vesicles within MVID patient tissues.

Other signs pointed to the expansion of immature cells in the upper crypt and lower villus, as well as faster shedding of enterocytes in the villus than in control animals. Scanning electron microscope images also showed immature and disorganized microvilli in the enterocytes of the patient-mimicking mice.

Taken together, “these findings are consistent with a deficit in enterocyte maturation in Myo5b(G519R) mice and in the patient with the MYO5B(G519R) mutation,” the authors wrote.

The authors suggest that their approach could be used more generally to quickly create mouse models of patient-specific monogenic congenital disorders.

The authors disclosed no conflicts of interest. The research was funded by the National Foundation of Science, National Institutes of Health, Vanderbilt Digestive Diseases Research Center Pilot and Feasibility grant, an American Physiological Society John F. Perkins, Jr. Research Career Enhancement Award, and a gift from the Christine Volpe Fund.

Researchers have identified a novel mutation in a patient with microvillus inclusion disease (MVID) and rapidly developed a specific mouse model to find insights into the disease process.

MVID is characterized by severe diarrhea, generally beginning within a few hours of birth. The condition is caused by inactivating mutations in the gene myosin VB (MYO5B). Affected individuals usually require lifetime use of total parenteral nutrition or small-bowel transplantation.

More than 100 MYO5B mutations have been identified in MVID patients, most of whom inherit two unique mutant alleles. This can lead to variability in phenotypes, which single-mutation animal models have been unable to mimic. Generally, patients have atrophy of microvilli on enterocytes as well as inclusion bodies within enterocytes that contain microvilli.

In the study, published in Cellular and Molecular Gastroenterology and Hepatology, researchers describe genetic sequencing of MYO5B mutations in a patient and both parents. One mutation is predicted to lead to protein truncation (c.1821delG), and the other (c.1555G>A) appeared to be inherited from the patient’s mother. The patient suffered from severe diarrhea after birth and was intermittently feeding intolerant.

The researchers conducted a range of diagnostic tests and biopsies. One particularly interesting finding was expression of the A-kinase anchoring protein 350 in the vicinity of the inclusion, wrote Andreanna Burman and her coauthors at Vanderbilt University, Nashville, Tenn. This protein takes part in a protein-mediating scaffolding pathway, suggesting that it could play a role in the development of the inclusions.

The researchers used multiplexed immunofluorescence (MxIF) staining of a biopsy of the duodenum to look for expression of a range of proteins. They found a striking decrease in enterocytes that express glucose transporter 2, implying that malabsorption might be due at least in part to enterocytes that fail to mature.

The patient also had internalization of apical nutrient transporters, which has been reported in other MVID patients. The researchers also developed a mouse model that incorporated the patient’s novel compound heterozygous genotype, which they cross-bred to produce a tamoxifen-inducible mouse model.

After the tamoxifen injection, the patient-mimicking animals exhibited a severe watery diarrhea, losing 19% of their body weight by day 4. The animals’ intestines showed a similar phenotype to that of the patient.

The apical sodium transporters sodium-glucose cotransporter 1 (SGLT1), apical sodium-dependent bile transporter, and NHE3 were internalized away from the apical membrane of the enterocytes in the patient-mimicking model animals. This structural difference may explain the limited absorption of sodium and water and the resultant watery diarrhea. The researchers also noted disruption of the actinin-4+ terminal web structure, as well as increased SGLT1 localization with lysosome-associated membrane protein 1+ lysosomes within the mouse model enterocytes. This association may indicate degradation of mislocalized proteins, the authors noted, which has also been seen in expanded RAB7+ vesicles within MVID patient tissues.

Other signs pointed to the expansion of immature cells in the upper crypt and lower villus, as well as faster shedding of enterocytes in the villus than in control animals. Scanning electron microscope images also showed immature and disorganized microvilli in the enterocytes of the patient-mimicking mice.

Taken together, “these findings are consistent with a deficit in enterocyte maturation in Myo5b(G519R) mice and in the patient with the MYO5B(G519R) mutation,” the authors wrote.

The authors suggest that their approach could be used more generally to quickly create mouse models of patient-specific monogenic congenital disorders.

The authors disclosed no conflicts of interest. The research was funded by the National Foundation of Science, National Institutes of Health, Vanderbilt Digestive Diseases Research Center Pilot and Feasibility grant, an American Physiological Society John F. Perkins, Jr. Research Career Enhancement Award, and a gift from the Christine Volpe Fund.

Practicing yoga was associated with improvements in several frailty markers in previously inactive older adults, a multistudy review finds.

“Up to 50% of adults aged 80 years or older are estimated to be frail, and the global prevalence is expected to rise given the aging of our population,” therefore more interventions are needed to help with frailty, corresponding author Julia Loewenthal, MD, said in an interview.

Yoga integrates across multiple body systems including the musculoskeletal system, nervous system, and others, said Dr. Loewenthal of Brigham and Women’s Hospital, Boston. Previous research has shown that yoga has a positive effect on cardiovascular risk factors, mood, and quality of life, but the effects of yoga on frailty have not been well studied.

“We wanted to evaluate whether [yoga] might help with frailty, since it touches on so many systems, as frailty does,” she noted.

In a systematic review published in Annals of Internal Medicine, the researchers identified 33 randomized, controlled trials of yoga-based interventions including 2,384 adults aged 65 years and older. The studies mainly involved Iyengar or chair-based yoga methods. The study population included community-dwelling seniors, nursing home residents, and individuals with chronic diseases.

The studies assessed the effect of a range of yoga practices on frailty markers including gait speed, handgrip strength, balance, lower extremity strength and endurance, and multicomponent measures of physical performance.

Overall, individuals who were randomized to engage in a yoga practice showed improved gait speed and lower extremity strength, compared with controls who were inactive or received an education intervention, with moderate-certainty evidence. The researchers also found low-certainty evidence in favor of yoga for improved balance and for a composite measure of physical function, and low-certainty evidence in favor of yoga for improved handgrip strength.

The findings were limited by several factors, mainly the heterogenous study designs, populations, and yoga styles, the researchers noted. Other limitations included the small sample sizes, variation in descriptions of the studies’ randomizations, and a lack of data on race and ethnicity of the participants.
 

Yoga’s role in healthy aging

“Overall, we were not surprised by the results since we have seen similar findings from other mind-body practices such as tai chi,” Dr. Loewenthal said in an interview. “We were surprised by the degree of improvement many of the participants had with gait speed.

“Yoga practices usually include a mix of poses in the standing, seated, and lying-down positions,” Dr. Loewenthal said. Some of the studies in the review also involved chair-based methods with few standing poses, and some involved gentle or slow-paced practices. “We know that many of the practices helped with leg strength, and perhaps they are also helping with coordination between the brain and body for walking.”

The findings suggest that clinicians can view yoga practice in general as part of a strategy to support healthy aging, Dr. Loewenthal said. “While our work looked at frailty markers and not overall frailty, I think it would be reasonable to offer yoga as a strategy along with already-established interventions such as resistance training and the Mediterranean diet, and if older adults are already practicing yoga, this could help them understand how the practice is impacting the aging process.”

There are many styles of yoga that overlap and are related to one another, so it is hard to make recommendations about a single type, said Dr. Loewenthal. Many of the studies in the review involved Iyengar yoga, named for yoga master B.K.S. Iyengar, which focuses on precise alignment and breath and seems to be conducive for older populations. Iyengar yoga also involves use of props such as blocks, bolsters, straps, and chairs, which makes it well suited for older individuals who may have a chronic condition or other limitations.

“Some styles of yoga are very physical and may reach energy expenditure and cardiovascular effects similar to aerobic exercise, but this is generally not the case for most styles of yoga,” she added.

As for additional research, “I think it is important that trials use a validated definition of frailty as an outcome; all of the trials in our study used markers of frailty but did not look at overall frailty,” said Dr. Loewenthal. In addition, it is important to understand how yoga affects people who have different levels of frailty, since previous research shows that those who are the most frail benefit most from physical activity interventions.
 

Yoga as an entry point for physical activity

With the increasing population of older adults in the United States and around the world, frailty is a major health concern because its association with significant declines in health and potential loss of independence, Amanda Paluch, PhD, said in an interview.

“Therefore, it is important to identify programs that can prevent frailty to support longevity and living independently for older adults. Yoga can be a feasible solution to promote movement and prevent frailty,” said Dr. Paluch, of the University of Massachusetts, Amherst, an assistant professor in the department of kinesiology and Institute for Applied Life Sciences.

“Other studies have demonstrated that light-intensity movement, as in yoga, may be particularly beneficial for older adults,” Dr. Paluch said. “Additionally, research has demonstrated that balance training activities are important to maintain physical function, prevent falls, and maintain their independence for older adults, so it makes sense that yoga was associated with lower likelihood of frailty.”

Although there may be additional benefits with higher intensity activity, “yoga could be a great place to start for older adults who are starting at low activity levels,” she said.

The takeaway for clinicians is to consider encouraging more physical activity for their patients to support healthy aging, including reducing the risk factors for frailty, said Dr. Paluch. “Particularly for older adults, physical activity may not need to be of high intensity for benefits. Activities such as yoga that focus on flexibility, balance, and movement at lower intensities can support healthy aging, and yoga may be a particularly good option for older adults who are least active.”

The study received no outside funding. The researchers and Dr. Paluch had no financial conflicts to disclose.

Practicing yoga was associated with improvements in several frailty markers in previously inactive older adults, a multistudy review finds.

“Up to 50% of adults aged 80 years or older are estimated to be frail, and the global prevalence is expected to rise given the aging of our population,” therefore more interventions are needed to help with frailty, corresponding author Julia Loewenthal, MD, said in an interview.

Yoga integrates across multiple body systems including the musculoskeletal system, nervous system, and others, said Dr. Loewenthal of Brigham and Women’s Hospital, Boston. Previous research has shown that yoga has a positive effect on cardiovascular risk factors, mood, and quality of life, but the effects of yoga on frailty have not been well studied.

“We wanted to evaluate whether [yoga] might help with frailty, since it touches on so many systems, as frailty does,” she noted.

In a systematic review published in Annals of Internal Medicine, the researchers identified 33 randomized, controlled trials of yoga-based interventions including 2,384 adults aged 65 years and older. The studies mainly involved Iyengar or chair-based yoga methods. The study population included community-dwelling seniors, nursing home residents, and individuals with chronic diseases.

The studies assessed the effect of a range of yoga practices on frailty markers including gait speed, handgrip strength, balance, lower extremity strength and endurance, and multicomponent measures of physical performance.

Overall, individuals who were randomized to engage in a yoga practice showed improved gait speed and lower extremity strength, compared with controls who were inactive or received an education intervention, with moderate-certainty evidence. The researchers also found low-certainty evidence in favor of yoga for improved balance and for a composite measure of physical function, and low-certainty evidence in favor of yoga for improved handgrip strength.

The findings were limited by several factors, mainly the heterogenous study designs, populations, and yoga styles, the researchers noted. Other limitations included the small sample sizes, variation in descriptions of the studies’ randomizations, and a lack of data on race and ethnicity of the participants.
 

Yoga’s role in healthy aging

“Overall, we were not surprised by the results since we have seen similar findings from other mind-body practices such as tai chi,” Dr. Loewenthal said in an interview. “We were surprised by the degree of improvement many of the participants had with gait speed.

“Yoga practices usually include a mix of poses in the standing, seated, and lying-down positions,” Dr. Loewenthal said. Some of the studies in the review also involved chair-based methods with few standing poses, and some involved gentle or slow-paced practices. “We know that many of the practices helped with leg strength, and perhaps they are also helping with coordination between the brain and body for walking.”

The findings suggest that clinicians can view yoga practice in general as part of a strategy to support healthy aging, Dr. Loewenthal said. “While our work looked at frailty markers and not overall frailty, I think it would be reasonable to offer yoga as a strategy along with already-established interventions such as resistance training and the Mediterranean diet, and if older adults are already practicing yoga, this could help them understand how the practice is impacting the aging process.”

There are many styles of yoga that overlap and are related to one another, so it is hard to make recommendations about a single type, said Dr. Loewenthal. Many of the studies in the review involved Iyengar yoga, named for yoga master B.K.S. Iyengar, which focuses on precise alignment and breath and seems to be conducive for older populations. Iyengar yoga also involves use of props such as blocks, bolsters, straps, and chairs, which makes it well suited for older individuals who may have a chronic condition or other limitations.

“Some styles of yoga are very physical and may reach energy expenditure and cardiovascular effects similar to aerobic exercise, but this is generally not the case for most styles of yoga,” she added.

As for additional research, “I think it is important that trials use a validated definition of frailty as an outcome; all of the trials in our study used markers of frailty but did not look at overall frailty,” said Dr. Loewenthal. In addition, it is important to understand how yoga affects people who have different levels of frailty, since previous research shows that those who are the most frail benefit most from physical activity interventions.
 

Yoga as an entry point for physical activity

With the increasing population of older adults in the United States and around the world, frailty is a major health concern because its association with significant declines in health and potential loss of independence, Amanda Paluch, PhD, said in an interview.

“Therefore, it is important to identify programs that can prevent frailty to support longevity and living independently for older adults. Yoga can be a feasible solution to promote movement and prevent frailty,” said Dr. Paluch, of the University of Massachusetts, Amherst, an assistant professor in the department of kinesiology and Institute for Applied Life Sciences.

“Other studies have demonstrated that light-intensity movement, as in yoga, may be particularly beneficial for older adults,” Dr. Paluch said. “Additionally, research has demonstrated that balance training activities are important to maintain physical function, prevent falls, and maintain their independence for older adults, so it makes sense that yoga was associated with lower likelihood of frailty.”

Although there may be additional benefits with higher intensity activity, “yoga could be a great place to start for older adults who are starting at low activity levels,” she said.

The takeaway for clinicians is to consider encouraging more physical activity for their patients to support healthy aging, including reducing the risk factors for frailty, said Dr. Paluch. “Particularly for older adults, physical activity may not need to be of high intensity for benefits. Activities such as yoga that focus on flexibility, balance, and movement at lower intensities can support healthy aging, and yoga may be a particularly good option for older adults who are least active.”

The study received no outside funding. The researchers and Dr. Paluch had no financial conflicts to disclose.

Practicing yoga was associated with improvements in several frailty markers in previously inactive older adults, a multistudy review finds.

“Up to 50% of adults aged 80 years or older are estimated to be frail, and the global prevalence is expected to rise given the aging of our population,” therefore more interventions are needed to help with frailty, corresponding author Julia Loewenthal, MD, said in an interview.

Yoga integrates across multiple body systems including the musculoskeletal system, nervous system, and others, said Dr. Loewenthal of Brigham and Women’s Hospital, Boston. Previous research has shown that yoga has a positive effect on cardiovascular risk factors, mood, and quality of life, but the effects of yoga on frailty have not been well studied.

“We wanted to evaluate whether [yoga] might help with frailty, since it touches on so many systems, as frailty does,” she noted.

In a systematic review published in Annals of Internal Medicine, the researchers identified 33 randomized, controlled trials of yoga-based interventions including 2,384 adults aged 65 years and older. The studies mainly involved Iyengar or chair-based yoga methods. The study population included community-dwelling seniors, nursing home residents, and individuals with chronic diseases.

The studies assessed the effect of a range of yoga practices on frailty markers including gait speed, handgrip strength, balance, lower extremity strength and endurance, and multicomponent measures of physical performance.

Overall, individuals who were randomized to engage in a yoga practice showed improved gait speed and lower extremity strength, compared with controls who were inactive or received an education intervention, with moderate-certainty evidence. The researchers also found low-certainty evidence in favor of yoga for improved balance and for a composite measure of physical function, and low-certainty evidence in favor of yoga for improved handgrip strength.

The findings were limited by several factors, mainly the heterogenous study designs, populations, and yoga styles, the researchers noted. Other limitations included the small sample sizes, variation in descriptions of the studies’ randomizations, and a lack of data on race and ethnicity of the participants.
 

Yoga’s role in healthy aging

“Overall, we were not surprised by the results since we have seen similar findings from other mind-body practices such as tai chi,” Dr. Loewenthal said in an interview. “We were surprised by the degree of improvement many of the participants had with gait speed.

“Yoga practices usually include a mix of poses in the standing, seated, and lying-down positions,” Dr. Loewenthal said. Some of the studies in the review also involved chair-based methods with few standing poses, and some involved gentle or slow-paced practices. “We know that many of the practices helped with leg strength, and perhaps they are also helping with coordination between the brain and body for walking.”

The findings suggest that clinicians can view yoga practice in general as part of a strategy to support healthy aging, Dr. Loewenthal said. “While our work looked at frailty markers and not overall frailty, I think it would be reasonable to offer yoga as a strategy along with already-established interventions such as resistance training and the Mediterranean diet, and if older adults are already practicing yoga, this could help them understand how the practice is impacting the aging process.”

There are many styles of yoga that overlap and are related to one another, so it is hard to make recommendations about a single type, said Dr. Loewenthal. Many of the studies in the review involved Iyengar yoga, named for yoga master B.K.S. Iyengar, which focuses on precise alignment and breath and seems to be conducive for older populations. Iyengar yoga also involves use of props such as blocks, bolsters, straps, and chairs, which makes it well suited for older individuals who may have a chronic condition or other limitations.

“Some styles of yoga are very physical and may reach energy expenditure and cardiovascular effects similar to aerobic exercise, but this is generally not the case for most styles of yoga,” she added.

As for additional research, “I think it is important that trials use a validated definition of frailty as an outcome; all of the trials in our study used markers of frailty but did not look at overall frailty,” said Dr. Loewenthal. In addition, it is important to understand how yoga affects people who have different levels of frailty, since previous research shows that those who are the most frail benefit most from physical activity interventions.
 

Yoga as an entry point for physical activity

With the increasing population of older adults in the United States and around the world, frailty is a major health concern because its association with significant declines in health and potential loss of independence, Amanda Paluch, PhD, said in an interview.

“Therefore, it is important to identify programs that can prevent frailty to support longevity and living independently for older adults. Yoga can be a feasible solution to promote movement and prevent frailty,” said Dr. Paluch, of the University of Massachusetts, Amherst, an assistant professor in the department of kinesiology and Institute for Applied Life Sciences.

“Other studies have demonstrated that light-intensity movement, as in yoga, may be particularly beneficial for older adults,” Dr. Paluch said. “Additionally, research has demonstrated that balance training activities are important to maintain physical function, prevent falls, and maintain their independence for older adults, so it makes sense that yoga was associated with lower likelihood of frailty.”

Although there may be additional benefits with higher intensity activity, “yoga could be a great place to start for older adults who are starting at low activity levels,” she said.

The takeaway for clinicians is to consider encouraging more physical activity for their patients to support healthy aging, including reducing the risk factors for frailty, said Dr. Paluch. “Particularly for older adults, physical activity may not need to be of high intensity for benefits. Activities such as yoga that focus on flexibility, balance, and movement at lower intensities can support healthy aging, and yoga may be a particularly good option for older adults who are least active.”

The study received no outside funding. The researchers and Dr. Paluch had no financial conflicts to disclose.

I was (probably) the bane of my elementary school nurse.

I hated PE (I know, who didn’t?). But I also had childhood asthma. So it was an easy out to go to the school nurse, Mrs. Reed, because I was having an asthma attack, or at least claiming to have one.

She’d put me in a chair to “keep an eye” on me, occasionally have me take the prescription drug my pediatrician had ordered (Marax – anyone else remember that?), and knew to send me back to class about 5 minutes before PE was over.

Maybe Mrs. Reed liked me. Maybe it was just the path of least resistance to let me dodge PE. Maybe she’d hated PE, too, and was sympathetic. Who knows?

So twice a week through years of elementary school she and I went through the same routine of my showing up in her office. No matter how busy she was, she always told me to take a seat and do a therapeutic application of her stethoscope. She often told others who noticed my frequent visits that I was “a sickly child” even though I knew she saw through me and said it with a sense of sarcasm and humor.

Of course, life goes on, and one day 20 years ago Mrs. Reed showed up on my hospital census as a new consult after she’d had a minor stroke.

She remembered me very well. Her first comment, said with the same tone I recalled, was that she was amazed I’d lived to adulthood after having been such “a sickly child.” We both laughed.

Now, in her late 80s, she still comes to see me for this and that. Sometimes we reminisce about the intertwined journey our lives have taken us on. Sometimes she asks if I’ve been to PE recently.

Like any patient, she occasionally shows up on the wrong day, or at the wrong time. I always do my best to see her, though.

After all, I owe her big time for letting me dodge PE.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I was (probably) the bane of my elementary school nurse.

I hated PE (I know, who didn’t?). But I also had childhood asthma. So it was an easy out to go to the school nurse, Mrs. Reed, because I was having an asthma attack, or at least claiming to have one.

She’d put me in a chair to “keep an eye” on me, occasionally have me take the prescription drug my pediatrician had ordered (Marax – anyone else remember that?), and knew to send me back to class about 5 minutes before PE was over.

Maybe Mrs. Reed liked me. Maybe it was just the path of least resistance to let me dodge PE. Maybe she’d hated PE, too, and was sympathetic. Who knows?

So twice a week through years of elementary school she and I went through the same routine of my showing up in her office. No matter how busy she was, she always told me to take a seat and do a therapeutic application of her stethoscope. She often told others who noticed my frequent visits that I was “a sickly child” even though I knew she saw through me and said it with a sense of sarcasm and humor.

Of course, life goes on, and one day 20 years ago Mrs. Reed showed up on my hospital census as a new consult after she’d had a minor stroke.

She remembered me very well. Her first comment, said with the same tone I recalled, was that she was amazed I’d lived to adulthood after having been such “a sickly child.” We both laughed.

Now, in her late 80s, she still comes to see me for this and that. Sometimes we reminisce about the intertwined journey our lives have taken us on. Sometimes she asks if I’ve been to PE recently.

Like any patient, she occasionally shows up on the wrong day, or at the wrong time. I always do my best to see her, though.

After all, I owe her big time for letting me dodge PE.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I was (probably) the bane of my elementary school nurse.

I hated PE (I know, who didn’t?). But I also had childhood asthma. So it was an easy out to go to the school nurse, Mrs. Reed, because I was having an asthma attack, or at least claiming to have one.

She’d put me in a chair to “keep an eye” on me, occasionally have me take the prescription drug my pediatrician had ordered (Marax – anyone else remember that?), and knew to send me back to class about 5 minutes before PE was over.

Maybe Mrs. Reed liked me. Maybe it was just the path of least resistance to let me dodge PE. Maybe she’d hated PE, too, and was sympathetic. Who knows?

So twice a week through years of elementary school she and I went through the same routine of my showing up in her office. No matter how busy she was, she always told me to take a seat and do a therapeutic application of her stethoscope. She often told others who noticed my frequent visits that I was “a sickly child” even though I knew she saw through me and said it with a sense of sarcasm and humor.

Of course, life goes on, and one day 20 years ago Mrs. Reed showed up on my hospital census as a new consult after she’d had a minor stroke.

She remembered me very well. Her first comment, said with the same tone I recalled, was that she was amazed I’d lived to adulthood after having been such “a sickly child.” We both laughed.

Now, in her late 80s, she still comes to see me for this and that. Sometimes we reminisce about the intertwined journey our lives have taken us on. Sometimes she asks if I’ve been to PE recently.

Like any patient, she occasionally shows up on the wrong day, or at the wrong time. I always do my best to see her, though.

After all, I owe her big time for letting me dodge PE.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

To defend the gut from microbes and pathogens, Paneth cells rely on TMEM16A, a calcium-activated chloride channel, and TMEM16F, a phospholipid scramblase, according to a new study published in Gastro Hep Advances.

The Paneth cells in mice missing TMEM16A or TMEM16F showed defects in signaling and release of secretary factors, researchers reported.

Inhibiting or activating TMEM16A and TMEM16F is likely to affect microbial content and immune functions in the small intestine, concluded Rainer Schreiber, Dr. rer. nat., of the Institute of Physiology at Universität Regensburg, Germany, and colleagues.

“Many small molecules and numerous natural or herbal compounds have been identified that either inhibit or activate TMEM16A or TMEM16F,” they wrote. “Some of these compounds may turn out to be useful therapeutics in inflammatory bowel disease, intestinal allergies, or abnormal colonization of the gut.”

Paneth cells play a central role in intestinal innate immune response, the authors wrote. Located at the base of small intestinal crypts and occasionally found in the proximal colon, these cells have defensive functions, such as protecting stem cells in response to invading microbes and eradicating ingested pathogens from intestinal crypts. Through secretion, they also regulate the composition and number of commensal intestinal bacteria. In inflammatory bowel disease, the Paneth cell zone expands due to an increase in cell size and cell number.

In previous studies, cholinergic stimulation provided enhanced protection in animals orally infected with virulent Salmonella enterica. However, the mechanisms of luminal stimulation of Paneth cell secretion in response to bacteria or lipopolysaccharide are unclear. Recent reports show that TMEM16A (also known as anoctamin 1, or ANO1) and TMEM16F (anoctamin 6, or ANO6) control intracellular calcium (Ca2+) signaling and that high local Ca2+ levels support exocytosis in intestinal cells.

The researchers analyzed the roles of the two molecules in Paneth cell secretion using mice with intestinal epithelial-specific knockout of TMEM16A or TMEM16F. They examined tissue structures and Paneth cells in the mice, as well as Paneth cell exocytosis in small intestinal organoids in vitro. They also compared Ca2+ signals between wild-type and knockout mice and analyzed bacterial colonization and intestinal apoptosis.

In wild-type mice, TMEM16A was detected at the apical pole of crypt epithelial cells, while TMEM16F was located predominantly at the basolateral side. Notably, TMEM16A was also located in intestinal smooth muscle cells.

Compared with wild-type mice, the TMEM16 knockout mice had pronounced accumulation of lysozyme in jejunal Paneth cells. This suggests a defect in Paneth cell secretion in the absence of TMEM16A and TMEM16F, the authors wrote.

Previous studies had found an accumulation of mucus in intestinal goblet cells in mice with tissue-specific knockout of TMEM16A and TMEM16F. In this study, a more detailed analysis of mucus using periodic acid-Schiff staining of duodenum, jejunum, and ileum confirmed those results and demonstrated enhanced mucus in the small intestine of knockout mice. This suggests that a lack of TMEM16A or TMEM16F causes a broad secretion defect in secretory cells, including Paneth cells, the authors wrote.

Because granules of Paneth cells contain antimicrobial peptides, cytokines, and other factors that control proliferation or epithelial cell death, the researchers analyzed the presence of Gram-positive and Gram-negative bacteria in the jejunum and ileum. Compared to wild-type mice, the number of bacteria was higher in the ileum of both TMEM16A and TMEM16F knockout mice and in the jejunum of TMEM16F knockout mice, suggesting reduced antimicrobial activity in the absence of TMEM16 proteins.

The researchers also compared regulated cell death of intestinal epithelial cells in jejuna of wild-type and knockout mice. They found largely reduced cell death in both TMEM16A and TMEM16F knockout mice.

“Intestinal inflammatory diseases such as Crohn’s disease, necrotizing enterocolitis, and intestinal microbiota dysbiosis have been related to abnormal Paneth cell physiology,” the authors wrote. “The present findings may therefore provide the basis for a novel anti-inflammatory therapy for intestinal diseases and may improve our understanding of the molecular mechanism of some of the currently available drugs.”

The study was supported by the Deutsche Forschungsgemeinschaft funding program. The authors disclosed no conflicts of interest.

To defend the gut from microbes and pathogens, Paneth cells rely on TMEM16A, a calcium-activated chloride channel, and TMEM16F, a phospholipid scramblase, according to a new study published in Gastro Hep Advances.

The Paneth cells in mice missing TMEM16A or TMEM16F showed defects in signaling and release of secretary factors, researchers reported.

Inhibiting or activating TMEM16A and TMEM16F is likely to affect microbial content and immune functions in the small intestine, concluded Rainer Schreiber, Dr. rer. nat., of the Institute of Physiology at Universität Regensburg, Germany, and colleagues.

“Many small molecules and numerous natural or herbal compounds have been identified that either inhibit or activate TMEM16A or TMEM16F,” they wrote. “Some of these compounds may turn out to be useful therapeutics in inflammatory bowel disease, intestinal allergies, or abnormal colonization of the gut.”

Paneth cells play a central role in intestinal innate immune response, the authors wrote. Located at the base of small intestinal crypts and occasionally found in the proximal colon, these cells have defensive functions, such as protecting stem cells in response to invading microbes and eradicating ingested pathogens from intestinal crypts. Through secretion, they also regulate the composition and number of commensal intestinal bacteria. In inflammatory bowel disease, the Paneth cell zone expands due to an increase in cell size and cell number.

In previous studies, cholinergic stimulation provided enhanced protection in animals orally infected with virulent Salmonella enterica. However, the mechanisms of luminal stimulation of Paneth cell secretion in response to bacteria or lipopolysaccharide are unclear. Recent reports show that TMEM16A (also known as anoctamin 1, or ANO1) and TMEM16F (anoctamin 6, or ANO6) control intracellular calcium (Ca2+) signaling and that high local Ca2+ levels support exocytosis in intestinal cells.

The researchers analyzed the roles of the two molecules in Paneth cell secretion using mice with intestinal epithelial-specific knockout of TMEM16A or TMEM16F. They examined tissue structures and Paneth cells in the mice, as well as Paneth cell exocytosis in small intestinal organoids in vitro. They also compared Ca2+ signals between wild-type and knockout mice and analyzed bacterial colonization and intestinal apoptosis.

In wild-type mice, TMEM16A was detected at the apical pole of crypt epithelial cells, while TMEM16F was located predominantly at the basolateral side. Notably, TMEM16A was also located in intestinal smooth muscle cells.

Compared with wild-type mice, the TMEM16 knockout mice had pronounced accumulation of lysozyme in jejunal Paneth cells. This suggests a defect in Paneth cell secretion in the absence of TMEM16A and TMEM16F, the authors wrote.

Previous studies had found an accumulation of mucus in intestinal goblet cells in mice with tissue-specific knockout of TMEM16A and TMEM16F. In this study, a more detailed analysis of mucus using periodic acid-Schiff staining of duodenum, jejunum, and ileum confirmed those results and demonstrated enhanced mucus in the small intestine of knockout mice. This suggests that a lack of TMEM16A or TMEM16F causes a broad secretion defect in secretory cells, including Paneth cells, the authors wrote.

Because granules of Paneth cells contain antimicrobial peptides, cytokines, and other factors that control proliferation or epithelial cell death, the researchers analyzed the presence of Gram-positive and Gram-negative bacteria in the jejunum and ileum. Compared to wild-type mice, the number of bacteria was higher in the ileum of both TMEM16A and TMEM16F knockout mice and in the jejunum of TMEM16F knockout mice, suggesting reduced antimicrobial activity in the absence of TMEM16 proteins.

The researchers also compared regulated cell death of intestinal epithelial cells in jejuna of wild-type and knockout mice. They found largely reduced cell death in both TMEM16A and TMEM16F knockout mice.

“Intestinal inflammatory diseases such as Crohn’s disease, necrotizing enterocolitis, and intestinal microbiota dysbiosis have been related to abnormal Paneth cell physiology,” the authors wrote. “The present findings may therefore provide the basis for a novel anti-inflammatory therapy for intestinal diseases and may improve our understanding of the molecular mechanism of some of the currently available drugs.”

The study was supported by the Deutsche Forschungsgemeinschaft funding program. The authors disclosed no conflicts of interest.

To defend the gut from microbes and pathogens, Paneth cells rely on TMEM16A, a calcium-activated chloride channel, and TMEM16F, a phospholipid scramblase, according to a new study published in Gastro Hep Advances.

The Paneth cells in mice missing TMEM16A or TMEM16F showed defects in signaling and release of secretary factors, researchers reported.

Inhibiting or activating TMEM16A and TMEM16F is likely to affect microbial content and immune functions in the small intestine, concluded Rainer Schreiber, Dr. rer. nat., of the Institute of Physiology at Universität Regensburg, Germany, and colleagues.

“Many small molecules and numerous natural or herbal compounds have been identified that either inhibit or activate TMEM16A or TMEM16F,” they wrote. “Some of these compounds may turn out to be useful therapeutics in inflammatory bowel disease, intestinal allergies, or abnormal colonization of the gut.”

Paneth cells play a central role in intestinal innate immune response, the authors wrote. Located at the base of small intestinal crypts and occasionally found in the proximal colon, these cells have defensive functions, such as protecting stem cells in response to invading microbes and eradicating ingested pathogens from intestinal crypts. Through secretion, they also regulate the composition and number of commensal intestinal bacteria. In inflammatory bowel disease, the Paneth cell zone expands due to an increase in cell size and cell number.

In previous studies, cholinergic stimulation provided enhanced protection in animals orally infected with virulent Salmonella enterica. However, the mechanisms of luminal stimulation of Paneth cell secretion in response to bacteria or lipopolysaccharide are unclear. Recent reports show that TMEM16A (also known as anoctamin 1, or ANO1) and TMEM16F (anoctamin 6, or ANO6) control intracellular calcium (Ca2+) signaling and that high local Ca2+ levels support exocytosis in intestinal cells.

The researchers analyzed the roles of the two molecules in Paneth cell secretion using mice with intestinal epithelial-specific knockout of TMEM16A or TMEM16F. They examined tissue structures and Paneth cells in the mice, as well as Paneth cell exocytosis in small intestinal organoids in vitro. They also compared Ca2+ signals between wild-type and knockout mice and analyzed bacterial colonization and intestinal apoptosis.

In wild-type mice, TMEM16A was detected at the apical pole of crypt epithelial cells, while TMEM16F was located predominantly at the basolateral side. Notably, TMEM16A was also located in intestinal smooth muscle cells.

Compared with wild-type mice, the TMEM16 knockout mice had pronounced accumulation of lysozyme in jejunal Paneth cells. This suggests a defect in Paneth cell secretion in the absence of TMEM16A and TMEM16F, the authors wrote.

Previous studies had found an accumulation of mucus in intestinal goblet cells in mice with tissue-specific knockout of TMEM16A and TMEM16F. In this study, a more detailed analysis of mucus using periodic acid-Schiff staining of duodenum, jejunum, and ileum confirmed those results and demonstrated enhanced mucus in the small intestine of knockout mice. This suggests that a lack of TMEM16A or TMEM16F causes a broad secretion defect in secretory cells, including Paneth cells, the authors wrote.

Because granules of Paneth cells contain antimicrobial peptides, cytokines, and other factors that control proliferation or epithelial cell death, the researchers analyzed the presence of Gram-positive and Gram-negative bacteria in the jejunum and ileum. Compared to wild-type mice, the number of bacteria was higher in the ileum of both TMEM16A and TMEM16F knockout mice and in the jejunum of TMEM16F knockout mice, suggesting reduced antimicrobial activity in the absence of TMEM16 proteins.

The researchers also compared regulated cell death of intestinal epithelial cells in jejuna of wild-type and knockout mice. They found largely reduced cell death in both TMEM16A and TMEM16F knockout mice.

“Intestinal inflammatory diseases such as Crohn’s disease, necrotizing enterocolitis, and intestinal microbiota dysbiosis have been related to abnormal Paneth cell physiology,” the authors wrote. “The present findings may therefore provide the basis for a novel anti-inflammatory therapy for intestinal diseases and may improve our understanding of the molecular mechanism of some of the currently available drugs.”

The study was supported by the Deutsche Forschungsgemeinschaft funding program. The authors disclosed no conflicts of interest.

A growing body of evidence shows that deeper and larger tumors can be safely removed with endoscopy instead of surgery when individual patient risk is taken into account, according to a review by Eva P.D. Verheij, a doctoral candidate at Amsterdam University Medical Center, and colleagues.

“Management of patients with superficial esophageal adenocarcinoma (EAC) is becoming less invasive and more patient-tailored,” the researchers wrote in Techniques and Innovations in Gastrointestinal Endoscopy. “In the future, watchful waiting may be a valid alternative to surgery in selected cases.”

Courtesy Eva P. D. Verheij

The investigators examined new advances that have been made in the management of superficial esophageal adenocarcinomas by endoscopy, and they address how guidelines may be falling short in light of newly published evidence.

Surgery is usually the first choice for the management of advanced esophageal adenocarcinoma. “Endoscopic treatment has become the cornerstone for early cancer confined to the mucosa,” the authors wrote.

“For low-risk submucosal EAC, which only invades the superficial submucosa (sm1, i.e. less than 500 mcm) without any other risk factors, endoscopic treatment as an alternative to surgery is gaining acceptance because multiple studies have demonstrated a very low risk of lymph node metastases (less than 2% for these lesions),” the investigators wrote. Although surgical resection with lymphadenectomy is currently the recommended treatment for cases with deep submucosal invasion, poor differentiation, or lymphovascular invasion, the investigators suggested that even these tumors may be within an endoscopist’s reach.

While the rate of lymph node metastasis for such patients has been reported to be as high as 46%, more recent endoscopic studies show a metastasis rate range of up to 20% after 23-63 months of follow-up.

“One possible explanation for the discrepancy in lymph node metastases rates between surgical and endoscopic studies could be the different preparation of slides for histopathological assessment,” the investigators wrote. “In general, the cuts in surgical specimen are made with wider intervals (±5 mm) than the cuts in endoscopic resection specimens (2-3 mm), with additional cuts in case of submucosal invasion. The hypothesis is that this wider interval may result in missing the area with the deepest tumor infiltration. This could result in an underdiagnosis of the actual invasion depth, and therefore an overestimation of the associated lymph node metastases risk.” A study published in August 2022 in Gastrointestinal Endoscopy found an annual metastases risk of 6.9% in patients with high-risk T1a EAC.

“Given its invasiveness and associated morbidity and mortality, esophagectomy may be overtreatment in those patients who will not develop lymph node metastases,” the investigators wrote. “Given the technical advances in endoscopy that enable us to radically remove large EACs, and to perform more meticulous follow-up, it might be time to swing the pendulum and only send those patients for surgery who have an indisputable indication for surgery, instead of performing esophagectomy as a prophylactic treatment.”

To truly find the limits of endoscopic resection for EAC, however, more research is needed.

“Ongoing studies are necessary to evaluate the lymph node metastases risk on an individual basis, using presence of histological risk factors. By predicting the risk of lymph node metastases, and considering patients’ wishes and condition, one might decide to perform esophagectomy or watchful waiting with strict endoscopic follow-up. In high-risk cases, we may use sentinel node navigated surgery in the future as an extra safety check before deciding on optimal management,” the authors wrote.

The investigators disclosed relationships Medtronic, C2 Therapeutics/Pentax Medical, MicroTech, and Aqua Medical.

A growing body of evidence shows that deeper and larger tumors can be safely removed with endoscopy instead of surgery when individual patient risk is taken into account, according to a review by Eva P.D. Verheij, a doctoral candidate at Amsterdam University Medical Center, and colleagues.

“Management of patients with superficial esophageal adenocarcinoma (EAC) is becoming less invasive and more patient-tailored,” the researchers wrote in Techniques and Innovations in Gastrointestinal Endoscopy. “In the future, watchful waiting may be a valid alternative to surgery in selected cases.”

Courtesy Eva P. D. Verheij

The investigators examined new advances that have been made in the management of superficial esophageal adenocarcinomas by endoscopy, and they address how guidelines may be falling short in light of newly published evidence.

Surgery is usually the first choice for the management of advanced esophageal adenocarcinoma. “Endoscopic treatment has become the cornerstone for early cancer confined to the mucosa,” the authors wrote.

“For low-risk submucosal EAC, which only invades the superficial submucosa (sm1, i.e. less than 500 mcm) without any other risk factors, endoscopic treatment as an alternative to surgery is gaining acceptance because multiple studies have demonstrated a very low risk of lymph node metastases (less than 2% for these lesions),” the investigators wrote. Although surgical resection with lymphadenectomy is currently the recommended treatment for cases with deep submucosal invasion, poor differentiation, or lymphovascular invasion, the investigators suggested that even these tumors may be within an endoscopist’s reach.

While the rate of lymph node metastasis for such patients has been reported to be as high as 46%, more recent endoscopic studies show a metastasis rate range of up to 20% after 23-63 months of follow-up.

“One possible explanation for the discrepancy in lymph node metastases rates between surgical and endoscopic studies could be the different preparation of slides for histopathological assessment,” the investigators wrote. “In general, the cuts in surgical specimen are made with wider intervals (±5 mm) than the cuts in endoscopic resection specimens (2-3 mm), with additional cuts in case of submucosal invasion. The hypothesis is that this wider interval may result in missing the area with the deepest tumor infiltration. This could result in an underdiagnosis of the actual invasion depth, and therefore an overestimation of the associated lymph node metastases risk.” A study published in August 2022 in Gastrointestinal Endoscopy found an annual metastases risk of 6.9% in patients with high-risk T1a EAC.

“Given its invasiveness and associated morbidity and mortality, esophagectomy may be overtreatment in those patients who will not develop lymph node metastases,” the investigators wrote. “Given the technical advances in endoscopy that enable us to radically remove large EACs, and to perform more meticulous follow-up, it might be time to swing the pendulum and only send those patients for surgery who have an indisputable indication for surgery, instead of performing esophagectomy as a prophylactic treatment.”

To truly find the limits of endoscopic resection for EAC, however, more research is needed.

“Ongoing studies are necessary to evaluate the lymph node metastases risk on an individual basis, using presence of histological risk factors. By predicting the risk of lymph node metastases, and considering patients’ wishes and condition, one might decide to perform esophagectomy or watchful waiting with strict endoscopic follow-up. In high-risk cases, we may use sentinel node navigated surgery in the future as an extra safety check before deciding on optimal management,” the authors wrote.

The investigators disclosed relationships Medtronic, C2 Therapeutics/Pentax Medical, MicroTech, and Aqua Medical.

A growing body of evidence shows that deeper and larger tumors can be safely removed with endoscopy instead of surgery when individual patient risk is taken into account, according to a review by Eva P.D. Verheij, a doctoral candidate at Amsterdam University Medical Center, and colleagues.

“Management of patients with superficial esophageal adenocarcinoma (EAC) is becoming less invasive and more patient-tailored,” the researchers wrote in Techniques and Innovations in Gastrointestinal Endoscopy. “In the future, watchful waiting may be a valid alternative to surgery in selected cases.”

Courtesy Eva P. D. Verheij

The investigators examined new advances that have been made in the management of superficial esophageal adenocarcinomas by endoscopy, and they address how guidelines may be falling short in light of newly published evidence.

Surgery is usually the first choice for the management of advanced esophageal adenocarcinoma. “Endoscopic treatment has become the cornerstone for early cancer confined to the mucosa,” the authors wrote.

“For low-risk submucosal EAC, which only invades the superficial submucosa (sm1, i.e. less than 500 mcm) without any other risk factors, endoscopic treatment as an alternative to surgery is gaining acceptance because multiple studies have demonstrated a very low risk of lymph node metastases (less than 2% for these lesions),” the investigators wrote. Although surgical resection with lymphadenectomy is currently the recommended treatment for cases with deep submucosal invasion, poor differentiation, or lymphovascular invasion, the investigators suggested that even these tumors may be within an endoscopist’s reach.

While the rate of lymph node metastasis for such patients has been reported to be as high as 46%, more recent endoscopic studies show a metastasis rate range of up to 20% after 23-63 months of follow-up.

“One possible explanation for the discrepancy in lymph node metastases rates between surgical and endoscopic studies could be the different preparation of slides for histopathological assessment,” the investigators wrote. “In general, the cuts in surgical specimen are made with wider intervals (±5 mm) than the cuts in endoscopic resection specimens (2-3 mm), with additional cuts in case of submucosal invasion. The hypothesis is that this wider interval may result in missing the area with the deepest tumor infiltration. This could result in an underdiagnosis of the actual invasion depth, and therefore an overestimation of the associated lymph node metastases risk.” A study published in August 2022 in Gastrointestinal Endoscopy found an annual metastases risk of 6.9% in patients with high-risk T1a EAC.

“Given its invasiveness and associated morbidity and mortality, esophagectomy may be overtreatment in those patients who will not develop lymph node metastases,” the investigators wrote. “Given the technical advances in endoscopy that enable us to radically remove large EACs, and to perform more meticulous follow-up, it might be time to swing the pendulum and only send those patients for surgery who have an indisputable indication for surgery, instead of performing esophagectomy as a prophylactic treatment.”

To truly find the limits of endoscopic resection for EAC, however, more research is needed.

“Ongoing studies are necessary to evaluate the lymph node metastases risk on an individual basis, using presence of histological risk factors. By predicting the risk of lymph node metastases, and considering patients’ wishes and condition, one might decide to perform esophagectomy or watchful waiting with strict endoscopic follow-up. In high-risk cases, we may use sentinel node navigated surgery in the future as an extra safety check before deciding on optimal management,” the authors wrote.

The investigators disclosed relationships Medtronic, C2 Therapeutics/Pentax Medical, MicroTech, and Aqua Medical.

In new evidence-based guidelines, the American Gastroenterological Association recommends noninvasive biomarkers as a first-line strategy for monitoring many patients with ulcerative colitis (UC). These guidelines were published in Gastroenterology.

The AGA guidelines outline use cases for three biomarkers that provide accurate insights into UC disease activity: serum C-reactive protein (CRP) (blood), fecal calprotectin (stool), and fecal lactoferrin (stool). AGA recommends a monitoring strategy that integrates noninvasive biomarkers for patients with UC in remission (no current symptoms) as well as those with current symptoms.
 

Patients with UC in symptomatic remission

• Perform interval biomarker monitoring every 6-12 months.
• AGA recommends stool-based biomarkers over blood testing.
• If biomarkers are normal, AGA suggests continuing biomarker monitoring and avoiding routine endoscopic assessment.
• If biomarkers are elevated, AGA suggests endoscopic assessment by a gastroenterologist.
• Listen to your body! Talk to your doctor about any new symptoms.

Patients with symptomatically active UC

• Biomarker testing should be the first step to determine the need for endoscopic assessment.
• For patients with mild symptoms who have normal or elevated biomarkers, AGA suggests endoscopic assessment by a gastroenterologist.
• For patients with moderate to severe symptoms who have normal biomarkers, AGA suggests endoscopic assessment by a gastroenterologist.
• For patients with moderate to severe symptoms and elevated biomarkers, AGA suggests treatment adjustment and avoiding endoscopic assessment.

With AGA guidelines guiding the use of noninvasive biomarkers, physicians can confidently offer a more convenient and closer monitoring option for their patients.

AGA will advocate for all insurers to cover the cost of biomarker testing in UC.

In new evidence-based guidelines, the American Gastroenterological Association recommends noninvasive biomarkers as a first-line strategy for monitoring many patients with ulcerative colitis (UC). These guidelines were published in Gastroenterology.

The AGA guidelines outline use cases for three biomarkers that provide accurate insights into UC disease activity: serum C-reactive protein (CRP) (blood), fecal calprotectin (stool), and fecal lactoferrin (stool). AGA recommends a monitoring strategy that integrates noninvasive biomarkers for patients with UC in remission (no current symptoms) as well as those with current symptoms.
 

Patients with UC in symptomatic remission

• Perform interval biomarker monitoring every 6-12 months.
• AGA recommends stool-based biomarkers over blood testing.
• If biomarkers are normal, AGA suggests continuing biomarker monitoring and avoiding routine endoscopic assessment.
• If biomarkers are elevated, AGA suggests endoscopic assessment by a gastroenterologist.
• Listen to your body! Talk to your doctor about any new symptoms.

Patients with symptomatically active UC

• Biomarker testing should be the first step to determine the need for endoscopic assessment.
• For patients with mild symptoms who have normal or elevated biomarkers, AGA suggests endoscopic assessment by a gastroenterologist.
• For patients with moderate to severe symptoms who have normal biomarkers, AGA suggests endoscopic assessment by a gastroenterologist.
• For patients with moderate to severe symptoms and elevated biomarkers, AGA suggests treatment adjustment and avoiding endoscopic assessment.

With AGA guidelines guiding the use of noninvasive biomarkers, physicians can confidently offer a more convenient and closer monitoring option for their patients.

AGA will advocate for all insurers to cover the cost of biomarker testing in UC.

In new evidence-based guidelines, the American Gastroenterological Association recommends noninvasive biomarkers as a first-line strategy for monitoring many patients with ulcerative colitis (UC). These guidelines were published in Gastroenterology.

The AGA guidelines outline use cases for three biomarkers that provide accurate insights into UC disease activity: serum C-reactive protein (CRP) (blood), fecal calprotectin (stool), and fecal lactoferrin (stool). AGA recommends a monitoring strategy that integrates noninvasive biomarkers for patients with UC in remission (no current symptoms) as well as those with current symptoms.
 

Patients with UC in symptomatic remission

• Perform interval biomarker monitoring every 6-12 months.
• AGA recommends stool-based biomarkers over blood testing.
• If biomarkers are normal, AGA suggests continuing biomarker monitoring and avoiding routine endoscopic assessment.
• If biomarkers are elevated, AGA suggests endoscopic assessment by a gastroenterologist.
• Listen to your body! Talk to your doctor about any new symptoms.

Patients with symptomatically active UC

• Biomarker testing should be the first step to determine the need for endoscopic assessment.
• For patients with mild symptoms who have normal or elevated biomarkers, AGA suggests endoscopic assessment by a gastroenterologist.
• For patients with moderate to severe symptoms who have normal biomarkers, AGA suggests endoscopic assessment by a gastroenterologist.
• For patients with moderate to severe symptoms and elevated biomarkers, AGA suggests treatment adjustment and avoiding endoscopic assessment.

With AGA guidelines guiding the use of noninvasive biomarkers, physicians can confidently offer a more convenient and closer monitoring option for their patients.

AGA will advocate for all insurers to cover the cost of biomarker testing in UC.

Medicare beneficiary cost sharing will no longer apply to the screening colonoscopy following a positive noninvasive stool-based screening test. To unlock this free benefit, providers must properly apply modifier KX.

What codes does this apply to?

Providers must append modifier KX (“requirements specified in the medical policy have been met”) to HCPCS codes G0105 and G0121 when the screening colonoscopy follows a positive result from one of the following noninvasive stool-based CRC screening tests:

• Screening Guaiac-based Fecal Occult Blood Test (gFOBT) (CPT 82270).
• Screening Immunoassay-based Fecal Occult Blood Test (iFOBT) (HCPCS G0328).
• Cologuard™ – Multi-target Stool DNA (sDNA) Test (CPT 81528).

What happens if I don’t use the KX modifier?

Medicare will return the screening colonoscopy claim as “unprocessable” and you will receive one of following messages:

CARC 16: “Claim/service lacks information or has submission billing error(s)” and RARC N822: “Missing Procedure Modifier(s)”

or

RARC N823: “Incomplete/Invalid Procedure Modifier”

Attach modifier KX and resubmit the claim to Medicare.
 

Should I use modifier KX if I remove polyps?

No. If you remove polyps during a screening colonoscopy following a positive noninvasive stool-based test, report the appropriate CPT code (for example, 45380, 45384, 45385, or 45388) and add modifier PT (colorectal cancer screening test; converted to diagnostic test or other procedure) to each CPT code for Medicare.

Some Medicare beneficiaries are not aware that Medicare has not fully eliminated the coinsurance responsibility yet when polypectomy is needed during a screening colonoscopy. Medicare beneficiary coinsurance responsibility is 15% of the cost of the procedure from 2023 to 2026. The coinsurance responsibility falls to 10% from 2027 to 2029 and by 2030 it will be covered 100% by Medicare.
 

Where can I find more information?

See the MLN Matters notice and the CMS Manual System.

Medicare beneficiary cost sharing will no longer apply to the screening colonoscopy following a positive noninvasive stool-based screening test. To unlock this free benefit, providers must properly apply modifier KX.

What codes does this apply to?

Providers must append modifier KX (“requirements specified in the medical policy have been met”) to HCPCS codes G0105 and G0121 when the screening colonoscopy follows a positive result from one of the following noninvasive stool-based CRC screening tests:

• Screening Guaiac-based Fecal Occult Blood Test (gFOBT) (CPT 82270).
• Screening Immunoassay-based Fecal Occult Blood Test (iFOBT) (HCPCS G0328).
• Cologuard™ – Multi-target Stool DNA (sDNA) Test (CPT 81528).

What happens if I don’t use the KX modifier?

Medicare will return the screening colonoscopy claim as “unprocessable” and you will receive one of following messages:

CARC 16: “Claim/service lacks information or has submission billing error(s)” and RARC N822: “Missing Procedure Modifier(s)”

or

RARC N823: “Incomplete/Invalid Procedure Modifier”

Attach modifier KX and resubmit the claim to Medicare.
 

Should I use modifier KX if I remove polyps?

No. If you remove polyps during a screening colonoscopy following a positive noninvasive stool-based test, report the appropriate CPT code (for example, 45380, 45384, 45385, or 45388) and add modifier PT (colorectal cancer screening test; converted to diagnostic test or other procedure) to each CPT code for Medicare.

Some Medicare beneficiaries are not aware that Medicare has not fully eliminated the coinsurance responsibility yet when polypectomy is needed during a screening colonoscopy. Medicare beneficiary coinsurance responsibility is 15% of the cost of the procedure from 2023 to 2026. The coinsurance responsibility falls to 10% from 2027 to 2029 and by 2030 it will be covered 100% by Medicare.
 

Where can I find more information?

See the MLN Matters notice and the CMS Manual System.

Medicare beneficiary cost sharing will no longer apply to the screening colonoscopy following a positive noninvasive stool-based screening test. To unlock this free benefit, providers must properly apply modifier KX.

What codes does this apply to?

Providers must append modifier KX (“requirements specified in the medical policy have been met”) to HCPCS codes G0105 and G0121 when the screening colonoscopy follows a positive result from one of the following noninvasive stool-based CRC screening tests:

• Screening Guaiac-based Fecal Occult Blood Test (gFOBT) (CPT 82270).
• Screening Immunoassay-based Fecal Occult Blood Test (iFOBT) (HCPCS G0328).
• Cologuard™ – Multi-target Stool DNA (sDNA) Test (CPT 81528).

What happens if I don’t use the KX modifier?

Medicare will return the screening colonoscopy claim as “unprocessable” and you will receive one of following messages:

CARC 16: “Claim/service lacks information or has submission billing error(s)” and RARC N822: “Missing Procedure Modifier(s)”

or

RARC N823: “Incomplete/Invalid Procedure Modifier”

Attach modifier KX and resubmit the claim to Medicare.
 

Should I use modifier KX if I remove polyps?

No. If you remove polyps during a screening colonoscopy following a positive noninvasive stool-based test, report the appropriate CPT code (for example, 45380, 45384, 45385, or 45388) and add modifier PT (colorectal cancer screening test; converted to diagnostic test or other procedure) to each CPT code for Medicare.

Some Medicare beneficiaries are not aware that Medicare has not fully eliminated the coinsurance responsibility yet when polypectomy is needed during a screening colonoscopy. Medicare beneficiary coinsurance responsibility is 15% of the cost of the procedure from 2023 to 2026. The coinsurance responsibility falls to 10% from 2027 to 2029 and by 2030 it will be covered 100% by Medicare.
 

Where can I find more information?

See the MLN Matters notice and the CMS Manual System.

NEW ORLEANS – An investigational, first-in class agent that delivers a completely new type of intervention to patients with pulmonary arterial hypertension (PAH) scored a clear win in the STELLAR trial, the first to complete among three phase 3 trials that are testing this agent.

Sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved from baseline average 6-minute walk distance (6MWD) by a significant and clinically meaningful 40.8 meters, compared with placebo, for the trial’s primary efficacy endpoint (P < .001). The treatment also “delivered broad clinical benefit across multiple domains including hemodynamics, World Health Organization functional class, disease biomarkers, risk scores and patient-reported outcomes,” Marius M. Hoeper, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“These results establish the clinical utility of sotatercept, administered in combination with approved PAH therapies, as a new treatment for PAH,” added Dr. Hoeper, professor and deputy director of the department of respiratory medicine at Hannover (Germany) Medical School,

“The most important aspect was the hemodynamic improvement,” with sotatercept treatment, which led to an average 235 dyn/sec per cm⁻⁵ reduction in pulmonary vascular resistance from baseline and an average cut in pulmonary artery pressure of 13.9 mm Hg from baseline, compared with placebo, a result that’s “unheard of,” Dr. Hoeper said in a press conference during the meeting.

“With other tested agents we usually see very little improvement in pulmonary artery pressure. This is a signal that we achieved some reversing of the pathological changes in the pulmonary vessels that lead to” PAH, he added.

Simultaneously with his report the findings also appeared online in the New England Journal of Medicine.
 

‘A new hope’ for patients with PAH

Based on the reported findings, sotatercept is a “very exciting boutique molecule” that will “offer patients with PAH a very exciting new treatment,” commented Rhonda Cooper-DeHoff, PharmD, a designated discussant and a researcher at the University of Florida, Gainesville.

Mitchel L. Zoler/MDedge News

“This study is a new hope for patients with PAH. Until now, they’ve had really bad outcomes, but [in this study] we see significant differences in 6MWD, hemodynamics, and risk factors. Overall, I think the benefit is greater than the risk” it may pose to patients through potential adverse effects, commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, and another discussant at the meeting.

“The results are impressive” and “encouraging,” and “suggest that sotatercept may represent a new and clinically consequential addition to current medications for PAH,” wrote three clinicians from Canyons Region Intermountain Medical Center in Murray, Utah, in an editorial that accompanied the published report.

But the authors of the editorial also raised several cautions and concerns. They questioned the generalizability of the findings, noting that the patients with PAH enrolled in the study were all adults who were clinically stable and an average of more than 8 years out from their initial PAH diagnosis, and more than 90% were on stable treatment for PAH with two or three agents specific for treating the disorder. The study cohort also had a disproportionately high enrollment of patients with idiopathic (59%) or heritable (18%) forms of PAH, and the 15% of patients in the trial with connective tissue disease represented a disproportionately low prevalence of this PAH subtype.

The editorialists also called for “ongoing vigilance” for adverse effects from sotatercept treatment, although they acknowledged that the adverse effects reported to date from sotatercept are “largely reassuring.”
 

Death or clinical worsening cut by 84%

STELLAR randomized 323 patients at 91 sites in 21 countries with WHO Group 1 PAH and with WHO functional class II or III disease to receive either sotatercept or placebo for 24 weeks, with an option for treatment to continue beyond that until the last patient in the study reached 24 weeks on treatment, resulting in an overall median treatment duration of nearly 33 weeks.

In addition to the significant result for the primary endpoint, the 163 patients who received sotatercept had significant improvements, compared with 160 placebo-treated patients, for eight of nine secondary endpoints. The only secondary endpoint with a neutral result was for a measure of cognitive and emotional wellbeing, a parameter that was already at a normal level at baseline in most enrolled patients, Dr. Hoeper explained.

The incidence of either death or an event indicative of clinical worsening during the overall median follow-up of almost 33 weeks was 26.3% among the control patients and 5.5% among those who received sotatercept. This translated into a significant reduction for this endpoint of 84% with sotatercept treatment, compared with placebo.

The rates of treatment-emergent adverse events leading to discontinuation were roughly the same in the control and sotatercept arms, and the incidence of severe or serious treatment-emergent adverse events was higher among the control patients.

The most common adverse event on sotatercept was bleeding events, which occurred in 32% of those on sotatercept and in 16% of the control patients, but the events in the sotatercept arm were “mostly mild,” said Dr. Hoeper. The next most frequent adverse event during sotatercept treatment was appearance of telangiectasias, which occurred in 14% of those on sotatercept and in 4% of control patients.

“It’s an uncommon adverse event profile, but not unexpected for a drug with its mechanism of action,” he said.

Drug binds activin, a pathologic driver of PAH

Sotatercept is an engineered molecule that combines a section of a human immunoglobulin G molecule with a portion of the receptor for activin. This structure allows sotatercept to bind free activin molecules in a patient’s blood, thereby removing a key driver of the pulmonary vascular wall remodeling that is at the pathologic root of PAH.

“Hyperproliferation of blood vessel–wall cells” caused by activin signaling “is perhaps the most important driver of PAH,” Dr. Hoeper said. “Sotatercept allows us for the first time to target the underlying mechanism behind PAH.”

Still ongoing are the HYPERION and ZENITH phase 3 trials of sotatercept. HYPERION is enrolling patients with newly diagnosed or high-risk PAH and is expected to complete in 2028. ZENITH is enrolling patients with more advanced PAH and a higher mortality risk, with results expected in 2026.

Sotatercept has received “Breakthrough Therapy” designation and “Orphan Drug” designation by the Food and Drug Administration, and “Priority Medicines” designation and “Orphan Drug” designation by the European Medicines Agency for the treatment of PAH. One recent review estimated a worldwide PAH prevalence of about 3-4 cases/100,000, which for the United States translates into a total prevalence of perhaps 10,000-15,000 affected people.

STELLAR was funded by Acceleron Pharma, a subsidiary of Merck. Dr. Hoeper is a consultant to Acceleron. Dr. Cooper-DeHoff, Dr. Grapsa, and the authors of the editorial on STELLAR have no relevant disclosures.

NEW ORLEANS – An investigational, first-in class agent that delivers a completely new type of intervention to patients with pulmonary arterial hypertension (PAH) scored a clear win in the STELLAR trial, the first to complete among three phase 3 trials that are testing this agent.

Sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved from baseline average 6-minute walk distance (6MWD) by a significant and clinically meaningful 40.8 meters, compared with placebo, for the trial’s primary efficacy endpoint (P < .001). The treatment also “delivered broad clinical benefit across multiple domains including hemodynamics, World Health Organization functional class, disease biomarkers, risk scores and patient-reported outcomes,” Marius M. Hoeper, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“These results establish the clinical utility of sotatercept, administered in combination with approved PAH therapies, as a new treatment for PAH,” added Dr. Hoeper, professor and deputy director of the department of respiratory medicine at Hannover (Germany) Medical School,

“The most important aspect was the hemodynamic improvement,” with sotatercept treatment, which led to an average 235 dyn/sec per cm⁻⁵ reduction in pulmonary vascular resistance from baseline and an average cut in pulmonary artery pressure of 13.9 mm Hg from baseline, compared with placebo, a result that’s “unheard of,” Dr. Hoeper said in a press conference during the meeting.

“With other tested agents we usually see very little improvement in pulmonary artery pressure. This is a signal that we achieved some reversing of the pathological changes in the pulmonary vessels that lead to” PAH, he added.

Simultaneously with his report the findings also appeared online in the New England Journal of Medicine.
 

‘A new hope’ for patients with PAH

Based on the reported findings, sotatercept is a “very exciting boutique molecule” that will “offer patients with PAH a very exciting new treatment,” commented Rhonda Cooper-DeHoff, PharmD, a designated discussant and a researcher at the University of Florida, Gainesville.

Mitchel L. Zoler/MDedge News

“This study is a new hope for patients with PAH. Until now, they’ve had really bad outcomes, but [in this study] we see significant differences in 6MWD, hemodynamics, and risk factors. Overall, I think the benefit is greater than the risk” it may pose to patients through potential adverse effects, commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, and another discussant at the meeting.

“The results are impressive” and “encouraging,” and “suggest that sotatercept may represent a new and clinically consequential addition to current medications for PAH,” wrote three clinicians from Canyons Region Intermountain Medical Center in Murray, Utah, in an editorial that accompanied the published report.

But the authors of the editorial also raised several cautions and concerns. They questioned the generalizability of the findings, noting that the patients with PAH enrolled in the study were all adults who were clinically stable and an average of more than 8 years out from their initial PAH diagnosis, and more than 90% were on stable treatment for PAH with two or three agents specific for treating the disorder. The study cohort also had a disproportionately high enrollment of patients with idiopathic (59%) or heritable (18%) forms of PAH, and the 15% of patients in the trial with connective tissue disease represented a disproportionately low prevalence of this PAH subtype.

The editorialists also called for “ongoing vigilance” for adverse effects from sotatercept treatment, although they acknowledged that the adverse effects reported to date from sotatercept are “largely reassuring.”
 

Death or clinical worsening cut by 84%

STELLAR randomized 323 patients at 91 sites in 21 countries with WHO Group 1 PAH and with WHO functional class II or III disease to receive either sotatercept or placebo for 24 weeks, with an option for treatment to continue beyond that until the last patient in the study reached 24 weeks on treatment, resulting in an overall median treatment duration of nearly 33 weeks.

In addition to the significant result for the primary endpoint, the 163 patients who received sotatercept had significant improvements, compared with 160 placebo-treated patients, for eight of nine secondary endpoints. The only secondary endpoint with a neutral result was for a measure of cognitive and emotional wellbeing, a parameter that was already at a normal level at baseline in most enrolled patients, Dr. Hoeper explained.

The incidence of either death or an event indicative of clinical worsening during the overall median follow-up of almost 33 weeks was 26.3% among the control patients and 5.5% among those who received sotatercept. This translated into a significant reduction for this endpoint of 84% with sotatercept treatment, compared with placebo.

The rates of treatment-emergent adverse events leading to discontinuation were roughly the same in the control and sotatercept arms, and the incidence of severe or serious treatment-emergent adverse events was higher among the control patients.

The most common adverse event on sotatercept was bleeding events, which occurred in 32% of those on sotatercept and in 16% of the control patients, but the events in the sotatercept arm were “mostly mild,” said Dr. Hoeper. The next most frequent adverse event during sotatercept treatment was appearance of telangiectasias, which occurred in 14% of those on sotatercept and in 4% of control patients.

“It’s an uncommon adverse event profile, but not unexpected for a drug with its mechanism of action,” he said.

Drug binds activin, a pathologic driver of PAH

Sotatercept is an engineered molecule that combines a section of a human immunoglobulin G molecule with a portion of the receptor for activin. This structure allows sotatercept to bind free activin molecules in a patient’s blood, thereby removing a key driver of the pulmonary vascular wall remodeling that is at the pathologic root of PAH.

“Hyperproliferation of blood vessel–wall cells” caused by activin signaling “is perhaps the most important driver of PAH,” Dr. Hoeper said. “Sotatercept allows us for the first time to target the underlying mechanism behind PAH.”

Still ongoing are the HYPERION and ZENITH phase 3 trials of sotatercept. HYPERION is enrolling patients with newly diagnosed or high-risk PAH and is expected to complete in 2028. ZENITH is enrolling patients with more advanced PAH and a higher mortality risk, with results expected in 2026.

Sotatercept has received “Breakthrough Therapy” designation and “Orphan Drug” designation by the Food and Drug Administration, and “Priority Medicines” designation and “Orphan Drug” designation by the European Medicines Agency for the treatment of PAH. One recent review estimated a worldwide PAH prevalence of about 3-4 cases/100,000, which for the United States translates into a total prevalence of perhaps 10,000-15,000 affected people.

STELLAR was funded by Acceleron Pharma, a subsidiary of Merck. Dr. Hoeper is a consultant to Acceleron. Dr. Cooper-DeHoff, Dr. Grapsa, and the authors of the editorial on STELLAR have no relevant disclosures.

NEW ORLEANS – An investigational, first-in class agent that delivers a completely new type of intervention to patients with pulmonary arterial hypertension (PAH) scored a clear win in the STELLAR trial, the first to complete among three phase 3 trials that are testing this agent.

Sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved from baseline average 6-minute walk distance (6MWD) by a significant and clinically meaningful 40.8 meters, compared with placebo, for the trial’s primary efficacy endpoint (P < .001). The treatment also “delivered broad clinical benefit across multiple domains including hemodynamics, World Health Organization functional class, disease biomarkers, risk scores and patient-reported outcomes,” Marius M. Hoeper, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“These results establish the clinical utility of sotatercept, administered in combination with approved PAH therapies, as a new treatment for PAH,” added Dr. Hoeper, professor and deputy director of the department of respiratory medicine at Hannover (Germany) Medical School,

“The most important aspect was the hemodynamic improvement,” with sotatercept treatment, which led to an average 235 dyn/sec per cm⁻⁵ reduction in pulmonary vascular resistance from baseline and an average cut in pulmonary artery pressure of 13.9 mm Hg from baseline, compared with placebo, a result that’s “unheard of,” Dr. Hoeper said in a press conference during the meeting.

“With other tested agents we usually see very little improvement in pulmonary artery pressure. This is a signal that we achieved some reversing of the pathological changes in the pulmonary vessels that lead to” PAH, he added.

Simultaneously with his report the findings also appeared online in the New England Journal of Medicine.
 

‘A new hope’ for patients with PAH

Based on the reported findings, sotatercept is a “very exciting boutique molecule” that will “offer patients with PAH a very exciting new treatment,” commented Rhonda Cooper-DeHoff, PharmD, a designated discussant and a researcher at the University of Florida, Gainesville.

Mitchel L. Zoler/MDedge News

“This study is a new hope for patients with PAH. Until now, they’ve had really bad outcomes, but [in this study] we see significant differences in 6MWD, hemodynamics, and risk factors. Overall, I think the benefit is greater than the risk” it may pose to patients through potential adverse effects, commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, and another discussant at the meeting.

“The results are impressive” and “encouraging,” and “suggest that sotatercept may represent a new and clinically consequential addition to current medications for PAH,” wrote three clinicians from Canyons Region Intermountain Medical Center in Murray, Utah, in an editorial that accompanied the published report.

But the authors of the editorial also raised several cautions and concerns. They questioned the generalizability of the findings, noting that the patients with PAH enrolled in the study were all adults who were clinically stable and an average of more than 8 years out from their initial PAH diagnosis, and more than 90% were on stable treatment for PAH with two or three agents specific for treating the disorder. The study cohort also had a disproportionately high enrollment of patients with idiopathic (59%) or heritable (18%) forms of PAH, and the 15% of patients in the trial with connective tissue disease represented a disproportionately low prevalence of this PAH subtype.

The editorialists also called for “ongoing vigilance” for adverse effects from sotatercept treatment, although they acknowledged that the adverse effects reported to date from sotatercept are “largely reassuring.”
 

Death or clinical worsening cut by 84%

STELLAR randomized 323 patients at 91 sites in 21 countries with WHO Group 1 PAH and with WHO functional class II or III disease to receive either sotatercept or placebo for 24 weeks, with an option for treatment to continue beyond that until the last patient in the study reached 24 weeks on treatment, resulting in an overall median treatment duration of nearly 33 weeks.

In addition to the significant result for the primary endpoint, the 163 patients who received sotatercept had significant improvements, compared with 160 placebo-treated patients, for eight of nine secondary endpoints. The only secondary endpoint with a neutral result was for a measure of cognitive and emotional wellbeing, a parameter that was already at a normal level at baseline in most enrolled patients, Dr. Hoeper explained.

The incidence of either death or an event indicative of clinical worsening during the overall median follow-up of almost 33 weeks was 26.3% among the control patients and 5.5% among those who received sotatercept. This translated into a significant reduction for this endpoint of 84% with sotatercept treatment, compared with placebo.

The rates of treatment-emergent adverse events leading to discontinuation were roughly the same in the control and sotatercept arms, and the incidence of severe or serious treatment-emergent adverse events was higher among the control patients.

The most common adverse event on sotatercept was bleeding events, which occurred in 32% of those on sotatercept and in 16% of the control patients, but the events in the sotatercept arm were “mostly mild,” said Dr. Hoeper. The next most frequent adverse event during sotatercept treatment was appearance of telangiectasias, which occurred in 14% of those on sotatercept and in 4% of control patients.

“It’s an uncommon adverse event profile, but not unexpected for a drug with its mechanism of action,” he said.

Drug binds activin, a pathologic driver of PAH

Sotatercept is an engineered molecule that combines a section of a human immunoglobulin G molecule with a portion of the receptor for activin. This structure allows sotatercept to bind free activin molecules in a patient’s blood, thereby removing a key driver of the pulmonary vascular wall remodeling that is at the pathologic root of PAH.

“Hyperproliferation of blood vessel–wall cells” caused by activin signaling “is perhaps the most important driver of PAH,” Dr. Hoeper said. “Sotatercept allows us for the first time to target the underlying mechanism behind PAH.”

Still ongoing are the HYPERION and ZENITH phase 3 trials of sotatercept. HYPERION is enrolling patients with newly diagnosed or high-risk PAH and is expected to complete in 2028. ZENITH is enrolling patients with more advanced PAH and a higher mortality risk, with results expected in 2026.

Sotatercept has received “Breakthrough Therapy” designation and “Orphan Drug” designation by the Food and Drug Administration, and “Priority Medicines” designation and “Orphan Drug” designation by the European Medicines Agency for the treatment of PAH. One recent review estimated a worldwide PAH prevalence of about 3-4 cases/100,000, which for the United States translates into a total prevalence of perhaps 10,000-15,000 affected people.

STELLAR was funded by Acceleron Pharma, a subsidiary of Merck. Dr. Hoeper is a consultant to Acceleron. Dr. Cooper-DeHoff, Dr. Grapsa, and the authors of the editorial on STELLAR have no relevant disclosures.