Dear colleagues,

Innovation is the livelihood of our field, driving major advances in endoscopy and attracting many of us to Gastroenterology. From the development of endoscopic retrograde cholangiopancreatography to the wide-spread adoption of third space endoscopy, we continue to push the boundaries of our practice. But what is the next big disruption in GI, and how will it impact us? In this issue of Perspectives, two experts present their thoughts on current hot topics in GI. Dr. Jeremy Glissen Brown discusses the application of artificial intelligence in GI highlighting its promise but also raising important questions. Dr. Raman Muthusamy elaborates on single-use endoscopes – are they the wave of the future in preventing infection and meeting patient preference? Or will their long-term cost and environmental impact limit their use? I welcome your own thoughts on disruptive innovation in Gastroenterology – share with us on Twitter @AGA_GIHN and by email at [email protected].

Gyanprakash A. Ketwaroo, MD, MSc, is an associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.

The AI revolution, with some important caveats

BY JEREMY R. GLISSEN BROWN, MD, MSC

In 2018, Japan’s Pharmaceutical and Medical Device Agency approved the first artificial intelligence (AI)–based tool, a computer-aided diagnosis system (CADx) for use in clinical practice.¹ Since that time, we have seen regulatory approval for a variety of deep learning and AI-based tools in endoscopy and beyond. In addition, there has been an enormous amount of commercial and research interest in AI-based tools in clinical medicine and gastroenterology, and it is almost impossible to open a major gastroenterology journal or go to an academic conference without encountering a slew of AI-based projects.

Many thought and industry leaders say that we are in the midst of an AI revolution in gastroenterology. Indeed, we are at a period of unprecedented growth for deep learning and AI for several reasons, including a recent shift toward data-driven approaches, advancement of machine-learning techniques, and increased computing power. There is, however, also an unprecedented amount of scrutiny and thoughtful conversation about the role AI might play in clinical practice and how we use and regulate these tools in the clinical setting. We are thus in a unique position to ask ourselves the essential question: “Are we on the cusp of an AI revolution in gastroenterology, or are we seeing the release of medical software that is perhaps at best useful in a niche environment and at worse a hype-driven novelty without much clinical benefit?” We will use the most popular use-case, computer aided detection (CADe) of polyps in the colon, to explore this question. In the end, I believe that deep-learning technology will fundamentally change the way we practice gastroenterology. However, this is the perfect time to explore what this means now, and what we can do to shape what it will mean for the future.

CADe: Promise and questions

CADe is a computer vision task that involves localization, such as finding a polyp during colonoscopy and highlighting it with a hollow box. CADe in colonoscopy is perhaps the most well-studied application of deep learning in GI endoscopy to date and is furthest along in the development-implementation pipeline. Because of this, it is an ideal use-case for examining both the evidence that currently supports its use as well as the questions that have come up as we are starting to see CADe algorithms deployed in clinical practice. It is honestly astounding to think that, just 5 years ago, we were talking about CADe as a research concept. While early efforts applying traditional machine learning date back at least to the 1990s, we started to see prospective studies of CADe systems with undetectable or nearly undetectable latency in 2019.² Since that time we have seen the publication of at least 10 randomized clinical trials involving CADe.

CADe clearly has an impact on some of the conventional quality metrics we use for colonoscopy. While there is considerable heterogeneity in region and design among these trials, most show a significant increase in adenoma detection rate (ADR) and adenomas per colonoscopy. Tandem studies show decreases in adenoma miss rate, and at least one study showed a decrease in sessile serrated lesion miss rate as well. In one of the first randomized, controlled trials across multiple endoscopy centers in Italy, Repici and colleagues showed an increase in ADR from 40.4% in the control group to 54.8% in the CADe group (RR, 1.30; 95% confidence interval, 1.14-1.45).3 Because of pioneering trials such as this one, there are currently several CADe systems that have received regulatory approval in Europe, Asia, and the United States and are being deployed commercially.

It is also clear that the technology is there. In clinical practice, the Food and Drug Administration–approved systems work smoothly, with little to no detectable latency and generally low false-positive and false-negative rates. With clinical deployment, however, we have seen the emergence of healthy debate surrounding every aspect of this task-specific AI. On the development side, important questions include transparency of development data, ensuring that algorithm development is ethical and equitable (as deep learning is susceptible to exacerbating human biases) and methods of data labeling. On the deployment level, important concerns include proper regulation of locked versus “open” algorithms and downstream effects on cost.

In addition, with CADe we have seen a variety of clinical questions crop up because of the novelty of the technology. These include the concern that the increase in ADR we have seen thus far is driven in large part by diminutive and small adenomas (with healthy debate in turn as to these entities’ influence on interval colorectal cancer rates), the effect CADe might have on fellowship training to detect polyps with the human eye, and whether the technology affects sessile serrated lesion detection rates or not. The great thing about such questions is that they have inspired novel research related to CADe in the clinical setting, including how CADe affects trainee ADR, how CADe affects gaze patterns, and how CADe affects recommended surveillance intervals.

CADx, novel applications, and the future

Though there is not space to expand in this particular forum, it is safe to say that with the advancement of CADx in endoscopy and colonoscopy, we have seen similar and novel questions come up. The beautiful thing about all of this is that we are just scratching the surface of what is achievable with deep learning. We have started to see novel projects utilizing deep-learning algorithms, from detecting cirrhosis on ECG to automatically classifying stool consistency on the Bristol Stool Scale from pictures of stool. I ultimately do think that the deployment of AI tools will fundamentally change the way we practice and think about gastroenterology. We are at an incredibly exciting time where we as physicians have the power to shape what that looks like, how we think about AI deployment and regulation and where we go from here.

Dr. Glissen Brown is with the division of gastroenterology and hepatology at Duke University Medical Center, Durham, N.C. He has served as a consultant for Medtronic.

References

1. Aisu N et al. PLOS Digital Health. 2021 Jan 18. doi: 10.1371/journal.pdig.0000001.

2. Wang P et al. Gut. 2019 Oct;68(10):1813-9.

3. Repici A et al. Gastroenterology. 2020 Aug;159(2):512-20.e7.

What’s the future of single-use endoscopes?

BY V. RAMAN MUTHUSAMY, MD, MAS

Single-use endoscopes have been proposed as a definitive solution to the risk of endoscope-transmitted infections. While these infections have been reported for several decades, they have traditionally been associated with identified breaches in the reprocessing protocol. In 2015, numerous cases of duodenoscope-transmitted infections were reported after endoscopic retrograde cholangiopancreatography (ERCP) procedures. Many, if not most, of these cases were not associated with identified deviations from standard high-level disinfection protocols and occurred at high-volume experienced facilities. A subsequent FDA postmarket surveillance study found contamination rates were linked with potentially pathogenic bacteria in approximately 5% of duodenoscopes. Thus, amid growing concerns about the ability to adequately clean these complex devices, these events prompted the development of single-use duodenoscopes. Given the multifactorial causes leading to contaminated duodenoscopes, the advantages of such single-use devices are their ability to ensure the elimination of the potential of infection transmission as these devices are never reused. In addition to this primary benefit, the ability to create single-use devices could lead to more easily available specialty scopes and allow variations in endoscope design that could improve ergonomics. Single-use devices may also expand the ability to provide endoscopic services by eliminating the need for device reprocessing equipment at low-volume sites. However, several concerns have been raised regarding their use, especially if it were to become widespread. These include issues of device quality and performance (potentially leading to more failed cases or adverse events), cost, their environmental impact and current uncertainty regarding their indications for use. Furthermore, new alternatives such as reusable devices with partially disposable components or future low-temperature sterilization options may minimize the need for such devices. We will briefly discuss these issues in more detail below.

Given that nearly all cases of GI device–transmitted infections where standard reprocessing protocols were followed have occurred in duodenoscopes, I will focus on single-use duodenoscopes in this article. It is important that we reassure our patients and colleagues that standard reprocessing appears to be extremely effective with all other types of devices, including elevator containing linear echoendoscopes. Studies investigating the causes of why duodenoscopes have primarily been associated with device-transmitted outbreaks have focused on the complexity of the elevator including its recesses, fixed end-cap and wire channels. However, culturing has shown that up to one-third of contamination may occur in the instrument channels or in the region of the biopsy cap, leading to some potential residual sites of infection even when newly developed reusable devices with disposable elevators/end-caps are utilized.¹ Another challenge with reprocessing is the ability to prove residual contamination does not exist. While culturing the devices after reprocessing is most used, it should be noted many sites with outbreaks failed to culture the culprit bacteria from the devices as accessing the sites of contamination can be challenging. The use of other markers of residual contamination such as ATP and tests for residual blood/protein have yielded variable results. Specifically, ATP testing has not correlated well with culture results but may be helpful in assessing the quality of manual cleaning.²

These challenges have made the concept of single-use devices more appealing given the lack of a need reprocess devices or validate cleaning efficacy. Currently, there are two FDA-approved devices on the market, but the published literature to date has largely involved one of these devices. To date, in four published studies that have assessed the clinical performance of single-use duodenoscopes in over 400 patients, procedural success rates have ranged from 91% to 97% with adverse event rates and endoscopist satisfaction scores comparable to reusable devices. Most of these users were expert biliary endoscopists and more data are needed regarding the performance of the device in lower-volume and nonexpert users. While indications for use in these studies have varied, I feel that there are four potential scenarios to utilize these devices: in patients with known multidrug-resistant organisms undergoing ERCP; to facilitate logistics/operations when a reusable device is not available; in critically ill patients who would not tolerate a scope-acquired infection; and in procedures associated with a risk of bacteremia.

While preliminary data suggest single-use duodenoscopes are safe and effective in expert hands, concerns exist regarding their implementation more broadly into clinical practice. First, the devices cost between $1,500-3,000, making them impractical for many health systems. One study estimated the break-even cost of the device to be $800-1,300 based on variation in site volume and device contamination rates.³ However, it should be noted that current enhanced reprocessing protocols for reusable devices may add an additional $75,000-$400,000 per year based on center volume.⁴ In the United States, there is currently payment by federal and some commercial payors that cover part or all of the device cost, but whether this will continue long-term is unclear. In addition, there is significant concern regarding the environmental impact of a broader mover to single-use devices. Reprocessing programs do exist for these devices, but detailed analyses regarding the environmental effects of a strategy using single-use versus reusable devices and the waste generated from each are needed.

Finally, while primarily created to avoid device-related infection transmission, other benefits can be realized with single-use devices. The potential for ergonomic enhancements (variable handle sizes or shaft stiffness, R- and L-handed scopes) as well as the creation of specialty devices (extra-long or thin devices, devices with special optical or rotational capabilities) may become more feasible with a single-use platform. Finally, the pace of endoscopic innovation and refinement is likely to quicken with a single use platform, and new advancements can be incorporated in a timelier manner.

Conclusion

In summary, I believe single-use devices offer the potential to improve the safety of endoscopic procedures as well as improve procedural access, enhance ergonomics, and foster and expedite device innovation. However, reductions in cost, refining their indications, and developing recycling programs to minimize their environmental impact will be essential before more widespread adoption is achieved.

Dr. Muthusamy is a professor of clinical medicine at the University of California, Los Angeles, and the medical director of endoscopy at the UCLA Health System. He reported relationships with Medtronic, Boston Scientific, Motus GI, Endogastric Solutions, and Capsovision.

References

1. Bartles RL et al. Gastrointest Endosc. 2018 Aug;88(2):306-13.e2.

2. Day LW et al. Gastrointest Endosc. 2021 Jan;93(1):11-33.e6.

3. Bang JY et al. Gut. 2019 Nov;68(11):1915-7.

4. Bomman S et al. Endosc Int Open. 2021 Aug 23;9(9):E1404-12.

Dear colleagues,

Innovation is the livelihood of our field, driving major advances in endoscopy and attracting many of us to Gastroenterology. From the development of endoscopic retrograde cholangiopancreatography to the wide-spread adoption of third space endoscopy, we continue to push the boundaries of our practice. But what is the next big disruption in GI, and how will it impact us? In this issue of Perspectives, two experts present their thoughts on current hot topics in GI. Dr. Jeremy Glissen Brown discusses the application of artificial intelligence in GI highlighting its promise but also raising important questions. Dr. Raman Muthusamy elaborates on single-use endoscopes – are they the wave of the future in preventing infection and meeting patient preference? Or will their long-term cost and environmental impact limit their use? I welcome your own thoughts on disruptive innovation in Gastroenterology – share with us on Twitter @AGA_GIHN and by email at [email protected].

Gyanprakash A. Ketwaroo, MD, MSc, is an associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.

The AI revolution, with some important caveats

BY JEREMY R. GLISSEN BROWN, MD, MSC

In 2018, Japan’s Pharmaceutical and Medical Device Agency approved the first artificial intelligence (AI)–based tool, a computer-aided diagnosis system (CADx) for use in clinical practice.¹ Since that time, we have seen regulatory approval for a variety of deep learning and AI-based tools in endoscopy and beyond. In addition, there has been an enormous amount of commercial and research interest in AI-based tools in clinical medicine and gastroenterology, and it is almost impossible to open a major gastroenterology journal or go to an academic conference without encountering a slew of AI-based projects.

Many thought and industry leaders say that we are in the midst of an AI revolution in gastroenterology. Indeed, we are at a period of unprecedented growth for deep learning and AI for several reasons, including a recent shift toward data-driven approaches, advancement of machine-learning techniques, and increased computing power. There is, however, also an unprecedented amount of scrutiny and thoughtful conversation about the role AI might play in clinical practice and how we use and regulate these tools in the clinical setting. We are thus in a unique position to ask ourselves the essential question: “Are we on the cusp of an AI revolution in gastroenterology, or are we seeing the release of medical software that is perhaps at best useful in a niche environment and at worse a hype-driven novelty without much clinical benefit?” We will use the most popular use-case, computer aided detection (CADe) of polyps in the colon, to explore this question. In the end, I believe that deep-learning technology will fundamentally change the way we practice gastroenterology. However, this is the perfect time to explore what this means now, and what we can do to shape what it will mean for the future.

CADe: Promise and questions

CADe is a computer vision task that involves localization, such as finding a polyp during colonoscopy and highlighting it with a hollow box. CADe in colonoscopy is perhaps the most well-studied application of deep learning in GI endoscopy to date and is furthest along in the development-implementation pipeline. Because of this, it is an ideal use-case for examining both the evidence that currently supports its use as well as the questions that have come up as we are starting to see CADe algorithms deployed in clinical practice. It is honestly astounding to think that, just 5 years ago, we were talking about CADe as a research concept. While early efforts applying traditional machine learning date back at least to the 1990s, we started to see prospective studies of CADe systems with undetectable or nearly undetectable latency in 2019.² Since that time we have seen the publication of at least 10 randomized clinical trials involving CADe.

CADe clearly has an impact on some of the conventional quality metrics we use for colonoscopy. While there is considerable heterogeneity in region and design among these trials, most show a significant increase in adenoma detection rate (ADR) and adenomas per colonoscopy. Tandem studies show decreases in adenoma miss rate, and at least one study showed a decrease in sessile serrated lesion miss rate as well. In one of the first randomized, controlled trials across multiple endoscopy centers in Italy, Repici and colleagues showed an increase in ADR from 40.4% in the control group to 54.8% in the CADe group (RR, 1.30; 95% confidence interval, 1.14-1.45).3 Because of pioneering trials such as this one, there are currently several CADe systems that have received regulatory approval in Europe, Asia, and the United States and are being deployed commercially.

It is also clear that the technology is there. In clinical practice, the Food and Drug Administration–approved systems work smoothly, with little to no detectable latency and generally low false-positive and false-negative rates. With clinical deployment, however, we have seen the emergence of healthy debate surrounding every aspect of this task-specific AI. On the development side, important questions include transparency of development data, ensuring that algorithm development is ethical and equitable (as deep learning is susceptible to exacerbating human biases) and methods of data labeling. On the deployment level, important concerns include proper regulation of locked versus “open” algorithms and downstream effects on cost.

In addition, with CADe we have seen a variety of clinical questions crop up because of the novelty of the technology. These include the concern that the increase in ADR we have seen thus far is driven in large part by diminutive and small adenomas (with healthy debate in turn as to these entities’ influence on interval colorectal cancer rates), the effect CADe might have on fellowship training to detect polyps with the human eye, and whether the technology affects sessile serrated lesion detection rates or not. The great thing about such questions is that they have inspired novel research related to CADe in the clinical setting, including how CADe affects trainee ADR, how CADe affects gaze patterns, and how CADe affects recommended surveillance intervals.

CADx, novel applications, and the future

Though there is not space to expand in this particular forum, it is safe to say that with the advancement of CADx in endoscopy and colonoscopy, we have seen similar and novel questions come up. The beautiful thing about all of this is that we are just scratching the surface of what is achievable with deep learning. We have started to see novel projects utilizing deep-learning algorithms, from detecting cirrhosis on ECG to automatically classifying stool consistency on the Bristol Stool Scale from pictures of stool. I ultimately do think that the deployment of AI tools will fundamentally change the way we practice and think about gastroenterology. We are at an incredibly exciting time where we as physicians have the power to shape what that looks like, how we think about AI deployment and regulation and where we go from here.

Dr. Glissen Brown is with the division of gastroenterology and hepatology at Duke University Medical Center, Durham, N.C. He has served as a consultant for Medtronic.

References

1. Aisu N et al. PLOS Digital Health. 2021 Jan 18. doi: 10.1371/journal.pdig.0000001.

2. Wang P et al. Gut. 2019 Oct;68(10):1813-9.

3. Repici A et al. Gastroenterology. 2020 Aug;159(2):512-20.e7.

What’s the future of single-use endoscopes?

BY V. RAMAN MUTHUSAMY, MD, MAS

Single-use endoscopes have been proposed as a definitive solution to the risk of endoscope-transmitted infections. While these infections have been reported for several decades, they have traditionally been associated with identified breaches in the reprocessing protocol. In 2015, numerous cases of duodenoscope-transmitted infections were reported after endoscopic retrograde cholangiopancreatography (ERCP) procedures. Many, if not most, of these cases were not associated with identified deviations from standard high-level disinfection protocols and occurred at high-volume experienced facilities. A subsequent FDA postmarket surveillance study found contamination rates were linked with potentially pathogenic bacteria in approximately 5% of duodenoscopes. Thus, amid growing concerns about the ability to adequately clean these complex devices, these events prompted the development of single-use duodenoscopes. Given the multifactorial causes leading to contaminated duodenoscopes, the advantages of such single-use devices are their ability to ensure the elimination of the potential of infection transmission as these devices are never reused. In addition to this primary benefit, the ability to create single-use devices could lead to more easily available specialty scopes and allow variations in endoscope design that could improve ergonomics. Single-use devices may also expand the ability to provide endoscopic services by eliminating the need for device reprocessing equipment at low-volume sites. However, several concerns have been raised regarding their use, especially if it were to become widespread. These include issues of device quality and performance (potentially leading to more failed cases or adverse events), cost, their environmental impact and current uncertainty regarding their indications for use. Furthermore, new alternatives such as reusable devices with partially disposable components or future low-temperature sterilization options may minimize the need for such devices. We will briefly discuss these issues in more detail below.

Given that nearly all cases of GI device–transmitted infections where standard reprocessing protocols were followed have occurred in duodenoscopes, I will focus on single-use duodenoscopes in this article. It is important that we reassure our patients and colleagues that standard reprocessing appears to be extremely effective with all other types of devices, including elevator containing linear echoendoscopes. Studies investigating the causes of why duodenoscopes have primarily been associated with device-transmitted outbreaks have focused on the complexity of the elevator including its recesses, fixed end-cap and wire channels. However, culturing has shown that up to one-third of contamination may occur in the instrument channels or in the region of the biopsy cap, leading to some potential residual sites of infection even when newly developed reusable devices with disposable elevators/end-caps are utilized.¹ Another challenge with reprocessing is the ability to prove residual contamination does not exist. While culturing the devices after reprocessing is most used, it should be noted many sites with outbreaks failed to culture the culprit bacteria from the devices as accessing the sites of contamination can be challenging. The use of other markers of residual contamination such as ATP and tests for residual blood/protein have yielded variable results. Specifically, ATP testing has not correlated well with culture results but may be helpful in assessing the quality of manual cleaning.²

These challenges have made the concept of single-use devices more appealing given the lack of a need reprocess devices or validate cleaning efficacy. Currently, there are two FDA-approved devices on the market, but the published literature to date has largely involved one of these devices. To date, in four published studies that have assessed the clinical performance of single-use duodenoscopes in over 400 patients, procedural success rates have ranged from 91% to 97% with adverse event rates and endoscopist satisfaction scores comparable to reusable devices. Most of these users were expert biliary endoscopists and more data are needed regarding the performance of the device in lower-volume and nonexpert users. While indications for use in these studies have varied, I feel that there are four potential scenarios to utilize these devices: in patients with known multidrug-resistant organisms undergoing ERCP; to facilitate logistics/operations when a reusable device is not available; in critically ill patients who would not tolerate a scope-acquired infection; and in procedures associated with a risk of bacteremia.

While preliminary data suggest single-use duodenoscopes are safe and effective in expert hands, concerns exist regarding their implementation more broadly into clinical practice. First, the devices cost between $1,500-3,000, making them impractical for many health systems. One study estimated the break-even cost of the device to be $800-1,300 based on variation in site volume and device contamination rates.³ However, it should be noted that current enhanced reprocessing protocols for reusable devices may add an additional $75,000-$400,000 per year based on center volume.⁴ In the United States, there is currently payment by federal and some commercial payors that cover part or all of the device cost, but whether this will continue long-term is unclear. In addition, there is significant concern regarding the environmental impact of a broader mover to single-use devices. Reprocessing programs do exist for these devices, but detailed analyses regarding the environmental effects of a strategy using single-use versus reusable devices and the waste generated from each are needed.

Finally, while primarily created to avoid device-related infection transmission, other benefits can be realized with single-use devices. The potential for ergonomic enhancements (variable handle sizes or shaft stiffness, R- and L-handed scopes) as well as the creation of specialty devices (extra-long or thin devices, devices with special optical or rotational capabilities) may become more feasible with a single-use platform. Finally, the pace of endoscopic innovation and refinement is likely to quicken with a single use platform, and new advancements can be incorporated in a timelier manner.

Conclusion

In summary, I believe single-use devices offer the potential to improve the safety of endoscopic procedures as well as improve procedural access, enhance ergonomics, and foster and expedite device innovation. However, reductions in cost, refining their indications, and developing recycling programs to minimize their environmental impact will be essential before more widespread adoption is achieved.

Dr. Muthusamy is a professor of clinical medicine at the University of California, Los Angeles, and the medical director of endoscopy at the UCLA Health System. He reported relationships with Medtronic, Boston Scientific, Motus GI, Endogastric Solutions, and Capsovision.

References

1. Bartles RL et al. Gastrointest Endosc. 2018 Aug;88(2):306-13.e2.

2. Day LW et al. Gastrointest Endosc. 2021 Jan;93(1):11-33.e6.

3. Bang JY et al. Gut. 2019 Nov;68(11):1915-7.

4. Bomman S et al. Endosc Int Open. 2021 Aug 23;9(9):E1404-12.

Dear colleagues,

Innovation is the livelihood of our field, driving major advances in endoscopy and attracting many of us to Gastroenterology. From the development of endoscopic retrograde cholangiopancreatography to the wide-spread adoption of third space endoscopy, we continue to push the boundaries of our practice. But what is the next big disruption in GI, and how will it impact us? In this issue of Perspectives, two experts present their thoughts on current hot topics in GI. Dr. Jeremy Glissen Brown discusses the application of artificial intelligence in GI highlighting its promise but also raising important questions. Dr. Raman Muthusamy elaborates on single-use endoscopes – are they the wave of the future in preventing infection and meeting patient preference? Or will their long-term cost and environmental impact limit their use? I welcome your own thoughts on disruptive innovation in Gastroenterology – share with us on Twitter @AGA_GIHN and by email at [email protected].

Gyanprakash A. Ketwaroo, MD, MSc, is an associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.

The AI revolution, with some important caveats

BY JEREMY R. GLISSEN BROWN, MD, MSC

In 2018, Japan’s Pharmaceutical and Medical Device Agency approved the first artificial intelligence (AI)–based tool, a computer-aided diagnosis system (CADx) for use in clinical practice.¹ Since that time, we have seen regulatory approval for a variety of deep learning and AI-based tools in endoscopy and beyond. In addition, there has been an enormous amount of commercial and research interest in AI-based tools in clinical medicine and gastroenterology, and it is almost impossible to open a major gastroenterology journal or go to an academic conference without encountering a slew of AI-based projects.

Many thought and industry leaders say that we are in the midst of an AI revolution in gastroenterology. Indeed, we are at a period of unprecedented growth for deep learning and AI for several reasons, including a recent shift toward data-driven approaches, advancement of machine-learning techniques, and increased computing power. There is, however, also an unprecedented amount of scrutiny and thoughtful conversation about the role AI might play in clinical practice and how we use and regulate these tools in the clinical setting. We are thus in a unique position to ask ourselves the essential question: “Are we on the cusp of an AI revolution in gastroenterology, or are we seeing the release of medical software that is perhaps at best useful in a niche environment and at worse a hype-driven novelty without much clinical benefit?” We will use the most popular use-case, computer aided detection (CADe) of polyps in the colon, to explore this question. In the end, I believe that deep-learning technology will fundamentally change the way we practice gastroenterology. However, this is the perfect time to explore what this means now, and what we can do to shape what it will mean for the future.

CADe: Promise and questions

CADe is a computer vision task that involves localization, such as finding a polyp during colonoscopy and highlighting it with a hollow box. CADe in colonoscopy is perhaps the most well-studied application of deep learning in GI endoscopy to date and is furthest along in the development-implementation pipeline. Because of this, it is an ideal use-case for examining both the evidence that currently supports its use as well as the questions that have come up as we are starting to see CADe algorithms deployed in clinical practice. It is honestly astounding to think that, just 5 years ago, we were talking about CADe as a research concept. While early efforts applying traditional machine learning date back at least to the 1990s, we started to see prospective studies of CADe systems with undetectable or nearly undetectable latency in 2019.² Since that time we have seen the publication of at least 10 randomized clinical trials involving CADe.

CADe clearly has an impact on some of the conventional quality metrics we use for colonoscopy. While there is considerable heterogeneity in region and design among these trials, most show a significant increase in adenoma detection rate (ADR) and adenomas per colonoscopy. Tandem studies show decreases in adenoma miss rate, and at least one study showed a decrease in sessile serrated lesion miss rate as well. In one of the first randomized, controlled trials across multiple endoscopy centers in Italy, Repici and colleagues showed an increase in ADR from 40.4% in the control group to 54.8% in the CADe group (RR, 1.30; 95% confidence interval, 1.14-1.45).3 Because of pioneering trials such as this one, there are currently several CADe systems that have received regulatory approval in Europe, Asia, and the United States and are being deployed commercially.

It is also clear that the technology is there. In clinical practice, the Food and Drug Administration–approved systems work smoothly, with little to no detectable latency and generally low false-positive and false-negative rates. With clinical deployment, however, we have seen the emergence of healthy debate surrounding every aspect of this task-specific AI. On the development side, important questions include transparency of development data, ensuring that algorithm development is ethical and equitable (as deep learning is susceptible to exacerbating human biases) and methods of data labeling. On the deployment level, important concerns include proper regulation of locked versus “open” algorithms and downstream effects on cost.

In addition, with CADe we have seen a variety of clinical questions crop up because of the novelty of the technology. These include the concern that the increase in ADR we have seen thus far is driven in large part by diminutive and small adenomas (with healthy debate in turn as to these entities’ influence on interval colorectal cancer rates), the effect CADe might have on fellowship training to detect polyps with the human eye, and whether the technology affects sessile serrated lesion detection rates or not. The great thing about such questions is that they have inspired novel research related to CADe in the clinical setting, including how CADe affects trainee ADR, how CADe affects gaze patterns, and how CADe affects recommended surveillance intervals.

CADx, novel applications, and the future

Though there is not space to expand in this particular forum, it is safe to say that with the advancement of CADx in endoscopy and colonoscopy, we have seen similar and novel questions come up. The beautiful thing about all of this is that we are just scratching the surface of what is achievable with deep learning. We have started to see novel projects utilizing deep-learning algorithms, from detecting cirrhosis on ECG to automatically classifying stool consistency on the Bristol Stool Scale from pictures of stool. I ultimately do think that the deployment of AI tools will fundamentally change the way we practice and think about gastroenterology. We are at an incredibly exciting time where we as physicians have the power to shape what that looks like, how we think about AI deployment and regulation and where we go from here.

Dr. Glissen Brown is with the division of gastroenterology and hepatology at Duke University Medical Center, Durham, N.C. He has served as a consultant for Medtronic.

References

1. Aisu N et al. PLOS Digital Health. 2021 Jan 18. doi: 10.1371/journal.pdig.0000001.

2. Wang P et al. Gut. 2019 Oct;68(10):1813-9.

3. Repici A et al. Gastroenterology. 2020 Aug;159(2):512-20.e7.

What’s the future of single-use endoscopes?

BY V. RAMAN MUTHUSAMY, MD, MAS

Single-use endoscopes have been proposed as a definitive solution to the risk of endoscope-transmitted infections. While these infections have been reported for several decades, they have traditionally been associated with identified breaches in the reprocessing protocol. In 2015, numerous cases of duodenoscope-transmitted infections were reported after endoscopic retrograde cholangiopancreatography (ERCP) procedures. Many, if not most, of these cases were not associated with identified deviations from standard high-level disinfection protocols and occurred at high-volume experienced facilities. A subsequent FDA postmarket surveillance study found contamination rates were linked with potentially pathogenic bacteria in approximately 5% of duodenoscopes. Thus, amid growing concerns about the ability to adequately clean these complex devices, these events prompted the development of single-use duodenoscopes. Given the multifactorial causes leading to contaminated duodenoscopes, the advantages of such single-use devices are their ability to ensure the elimination of the potential of infection transmission as these devices are never reused. In addition to this primary benefit, the ability to create single-use devices could lead to more easily available specialty scopes and allow variations in endoscope design that could improve ergonomics. Single-use devices may also expand the ability to provide endoscopic services by eliminating the need for device reprocessing equipment at low-volume sites. However, several concerns have been raised regarding their use, especially if it were to become widespread. These include issues of device quality and performance (potentially leading to more failed cases or adverse events), cost, their environmental impact and current uncertainty regarding their indications for use. Furthermore, new alternatives such as reusable devices with partially disposable components or future low-temperature sterilization options may minimize the need for such devices. We will briefly discuss these issues in more detail below.

Given that nearly all cases of GI device–transmitted infections where standard reprocessing protocols were followed have occurred in duodenoscopes, I will focus on single-use duodenoscopes in this article. It is important that we reassure our patients and colleagues that standard reprocessing appears to be extremely effective with all other types of devices, including elevator containing linear echoendoscopes. Studies investigating the causes of why duodenoscopes have primarily been associated with device-transmitted outbreaks have focused on the complexity of the elevator including its recesses, fixed end-cap and wire channels. However, culturing has shown that up to one-third of contamination may occur in the instrument channels or in the region of the biopsy cap, leading to some potential residual sites of infection even when newly developed reusable devices with disposable elevators/end-caps are utilized.¹ Another challenge with reprocessing is the ability to prove residual contamination does not exist. While culturing the devices after reprocessing is most used, it should be noted many sites with outbreaks failed to culture the culprit bacteria from the devices as accessing the sites of contamination can be challenging. The use of other markers of residual contamination such as ATP and tests for residual blood/protein have yielded variable results. Specifically, ATP testing has not correlated well with culture results but may be helpful in assessing the quality of manual cleaning.²

These challenges have made the concept of single-use devices more appealing given the lack of a need reprocess devices or validate cleaning efficacy. Currently, there are two FDA-approved devices on the market, but the published literature to date has largely involved one of these devices. To date, in four published studies that have assessed the clinical performance of single-use duodenoscopes in over 400 patients, procedural success rates have ranged from 91% to 97% with adverse event rates and endoscopist satisfaction scores comparable to reusable devices. Most of these users were expert biliary endoscopists and more data are needed regarding the performance of the device in lower-volume and nonexpert users. While indications for use in these studies have varied, I feel that there are four potential scenarios to utilize these devices: in patients with known multidrug-resistant organisms undergoing ERCP; to facilitate logistics/operations when a reusable device is not available; in critically ill patients who would not tolerate a scope-acquired infection; and in procedures associated with a risk of bacteremia.

While preliminary data suggest single-use duodenoscopes are safe and effective in expert hands, concerns exist regarding their implementation more broadly into clinical practice. First, the devices cost between $1,500-3,000, making them impractical for many health systems. One study estimated the break-even cost of the device to be $800-1,300 based on variation in site volume and device contamination rates.³ However, it should be noted that current enhanced reprocessing protocols for reusable devices may add an additional $75,000-$400,000 per year based on center volume.⁴ In the United States, there is currently payment by federal and some commercial payors that cover part or all of the device cost, but whether this will continue long-term is unclear. In addition, there is significant concern regarding the environmental impact of a broader mover to single-use devices. Reprocessing programs do exist for these devices, but detailed analyses regarding the environmental effects of a strategy using single-use versus reusable devices and the waste generated from each are needed.

Finally, while primarily created to avoid device-related infection transmission, other benefits can be realized with single-use devices. The potential for ergonomic enhancements (variable handle sizes or shaft stiffness, R- and L-handed scopes) as well as the creation of specialty devices (extra-long or thin devices, devices with special optical or rotational capabilities) may become more feasible with a single-use platform. Finally, the pace of endoscopic innovation and refinement is likely to quicken with a single use platform, and new advancements can be incorporated in a timelier manner.

Conclusion

In summary, I believe single-use devices offer the potential to improve the safety of endoscopic procedures as well as improve procedural access, enhance ergonomics, and foster and expedite device innovation. However, reductions in cost, refining their indications, and developing recycling programs to minimize their environmental impact will be essential before more widespread adoption is achieved.

Dr. Muthusamy is a professor of clinical medicine at the University of California, Los Angeles, and the medical director of endoscopy at the UCLA Health System. He reported relationships with Medtronic, Boston Scientific, Motus GI, Endogastric Solutions, and Capsovision.

References

1. Bartles RL et al. Gastrointest Endosc. 2018 Aug;88(2):306-13.e2.

2. Day LW et al. Gastrointest Endosc. 2021 Jan;93(1):11-33.e6.

3. Bang JY et al. Gut. 2019 Nov;68(11):1915-7.

4. Bomman S et al. Endosc Int Open. 2021 Aug 23;9(9):E1404-12.

In 2007 (coinciding with the inaugural year of GI & Hepatology News), the National Institutes of Health launched the initial phase of the Human Microbiome Project (HMP), marking an important milestone in our study and understanding of the gut microbiome. The HMP, which was supported by “only” approximately $20 million of funding in its first year, served as a catalyst for the development of computational tools, clinical protocols, and reference datasets for an emerging field that now approaches nearly $2 billion per year in market value of diagnostics and therapeutics.

Over the past 15 years, many important discoveries about the microbiome have been made, particularly in the fields of gastroenterology, hepatology, and nutrition. The transplantation of gut microbiome from one person to another has been shown to be more than 90% effective in the treatment of recurrent C. difficile infection, disrupting our current therapeutic algorithms of repetitive antibiotics. Other exciting discoveries have included the relationship between the gut microbiome and enteric nervous system, and its roles in the regulation of metabolism and obesity and in the progression of liver fibrosis and cancer.

ChrisChrisW/Getty Images

Looking ahead, several exciting areas related to digestive health and the microbiome are being prioritized, including the role of probiotics in nutrition, the complex relationship of the bidirectional “gut-brain” axis, and further development of analytics to define and deliver precision medicine across a wide range of digestive disorders. Without a doubt, emerging microbiome discoveries will be prominently featured in the pages of GI & Hepatology News over the coming years to keep our readers informed of these cutting-edge findings.

Dr. Rosenberg is medical director of the North Shore Endoscopy Center and director of clinical research at GI Alliance of Illinois in Gurnee, Ill. Dr. Rosenberg is a consultant for Aimmune Therapeutics and performs clinical research with Ferring Pharmaceuticals.

In 2007 (coinciding with the inaugural year of GI & Hepatology News), the National Institutes of Health launched the initial phase of the Human Microbiome Project (HMP), marking an important milestone in our study and understanding of the gut microbiome. The HMP, which was supported by “only” approximately $20 million of funding in its first year, served as a catalyst for the development of computational tools, clinical protocols, and reference datasets for an emerging field that now approaches nearly $2 billion per year in market value of diagnostics and therapeutics.

Over the past 15 years, many important discoveries about the microbiome have been made, particularly in the fields of gastroenterology, hepatology, and nutrition. The transplantation of gut microbiome from one person to another has been shown to be more than 90% effective in the treatment of recurrent C. difficile infection, disrupting our current therapeutic algorithms of repetitive antibiotics. Other exciting discoveries have included the relationship between the gut microbiome and enteric nervous system, and its roles in the regulation of metabolism and obesity and in the progression of liver fibrosis and cancer.

ChrisChrisW/Getty Images

Looking ahead, several exciting areas related to digestive health and the microbiome are being prioritized, including the role of probiotics in nutrition, the complex relationship of the bidirectional “gut-brain” axis, and further development of analytics to define and deliver precision medicine across a wide range of digestive disorders. Without a doubt, emerging microbiome discoveries will be prominently featured in the pages of GI & Hepatology News over the coming years to keep our readers informed of these cutting-edge findings.

Dr. Rosenberg is medical director of the North Shore Endoscopy Center and director of clinical research at GI Alliance of Illinois in Gurnee, Ill. Dr. Rosenberg is a consultant for Aimmune Therapeutics and performs clinical research with Ferring Pharmaceuticals.

In 2007 (coinciding with the inaugural year of GI & Hepatology News), the National Institutes of Health launched the initial phase of the Human Microbiome Project (HMP), marking an important milestone in our study and understanding of the gut microbiome. The HMP, which was supported by “only” approximately $20 million of funding in its first year, served as a catalyst for the development of computational tools, clinical protocols, and reference datasets for an emerging field that now approaches nearly $2 billion per year in market value of diagnostics and therapeutics.

Over the past 15 years, many important discoveries about the microbiome have been made, particularly in the fields of gastroenterology, hepatology, and nutrition. The transplantation of gut microbiome from one person to another has been shown to be more than 90% effective in the treatment of recurrent C. difficile infection, disrupting our current therapeutic algorithms of repetitive antibiotics. Other exciting discoveries have included the relationship between the gut microbiome and enteric nervous system, and its roles in the regulation of metabolism and obesity and in the progression of liver fibrosis and cancer.

ChrisChrisW/Getty Images

Looking ahead, several exciting areas related to digestive health and the microbiome are being prioritized, including the role of probiotics in nutrition, the complex relationship of the bidirectional “gut-brain” axis, and further development of analytics to define and deliver precision medicine across a wide range of digestive disorders. Without a doubt, emerging microbiome discoveries will be prominently featured in the pages of GI & Hepatology News over the coming years to keep our readers informed of these cutting-edge findings.

Dr. Rosenberg is medical director of the North Shore Endoscopy Center and director of clinical research at GI Alliance of Illinois in Gurnee, Ill. Dr. Rosenberg is a consultant for Aimmune Therapeutics and performs clinical research with Ferring Pharmaceuticals.

Can you talk about the evolution and treatment of human epidermal growth factor receptor 2 (HER2)-low breast cancer?

Dr. Abdou: Until recently, HER2 status had been defined as a positive or negative result, but this convention has evolved, and now a newly defined population with low levels of HER2 expression has been identified. This HER2-low population accounts for about 55% of all breast cancers. Previously, low HER2 expression levels were considered HER2-negative in clinical practice because HER2-targeted therapies had been considered ineffective in this setting. Patients with HER2-low disease therefore had limited targeted treatment options after progression on their primary therapy.

Now, new studies and clinical trials have opened the door to effective treatments for this cohort of patients. The clinical trial DESTINY-Breast04, which was presented at ASCO 2022, led to the first FDA approval in August 2022 of a targeted therapy option for patients with HER2-low breast cancer subtypes, reclassifying this cohort as a new targetable subset in breast cancer.

DESTINY-Breast04 was the first randomized clinical trial to show that targeting HER2 provides clinically meaningful benefits for patients with HER2-low metastatic breast cancer, not only patients with HER2-positive disease. The phase 3 study enrolled about 557 patients with hormone receptor (HR)-negative or -positive breast cancer and centrally confirmed HER2-low expression who were previously treated with 1 or 2 prior lines of chemotherapy. Patients were randomized to receive either the antibody–drug conjugate trastuzumab deruxtecan or physician’s choice of standard chemotherapy. The risk of disease progression was about 50% lower and the risk of death was about 36% lower with trastuzumab deruxtecan compared with chemotherapy.¹

These impressive and practice-changing results opened the door to a new treatment option for a substantial group of patients with HER2-low disease and significantly expanded the population of patients who can benefit from HER2-targeted therapy.

What molecular characteristics do you take into consideration to help determine whether patients are eligible for these targeted treatment options?

Dr. Abdou: As we said earlier, HER2 status should no longer be recorded as a binary result of either HER2-positive or HER2-negative. It is important to start routinely testing for the level of HER2 expression in the tumor. Obtaining these levels is done through commonly used immunohistochemical (IHC) assays that allow direct visualization of the HER2 protein. Breast tumors considered to be HER2-low are classified as IHC1+ or as IHC2+ with in situ hybridization or FISH-negative status.

HER2-low breast cancer consists of a heterogeneous group of breast cancers, most of which are HR-positive tumors, whereas about 20% are HR-negative tumors. While these tumors may have distinct molecular profiles leading to clinicopathological and prognostic differences within these groups—HR-positive tumors represent more luminal subtypes and HR-negative tumors tend to be predominantly basal-like subtypes—these distinctions do not necessarily affect patient eligibility for targeted therapy. The benefit of trastuzumab deruxtecan was seen in both subgroups, although the HR-positive population was much more well represented in the DESTINY-Breast04 study.

Other than the HER2 expression status, I also take into consideration the presence of clinical comorbidities, particularly pulmonary comorbidities or prior lung injuries. Trastuzumab deruxtecan can cause a potentially serious type of lung toxicity called interstitial lung disease (ILD). In DESTINY-Breast04, ILD developed in about 12% of patients in the trastuzumab deruxtecan group, with 3 deaths as a result.

Therefore, it’s important for us to carefully select these patients and closely monitor them while they’re on treatment.

What is next in the treatment of HER2-low breast cancer, and what would you like to see in the future?

Dr. Abdou: The exciting new field of HER2-low breast cancer has really opened the door to novel studies and clinical trials, several of which are exploring the role of antibody–drug conjugates in patients with metastatic HER2-low disease and others that are studying early-stage HER2-low breast cancer. In early-stage HER2-low breast cancer, we may potentially see an even greater benefit with these drugs because the disease has not yet developed resistance to therapy. Other studies are examining the role of combination therapy in metastatic breast cancer, such as antibody–drug conjugates in combination with immunotherapy and other targeted agents. I look forward to results from those studies.

Also, importantly, as we start using these therapies more widely, I would like to see more accurate and sensitive ways of assessing the HER2 expression status. The current IHC assay, although widely available, fails to identify many women who have HER2 expression in their tumors. I think more sensitive tests may be able to identify even more women who can benefit from these targeted therapies.

Can you talk about the evolution and treatment of human epidermal growth factor receptor 2 (HER2)-low breast cancer?

Dr. Abdou: Until recently, HER2 status had been defined as a positive or negative result, but this convention has evolved, and now a newly defined population with low levels of HER2 expression has been identified. This HER2-low population accounts for about 55% of all breast cancers. Previously, low HER2 expression levels were considered HER2-negative in clinical practice because HER2-targeted therapies had been considered ineffective in this setting. Patients with HER2-low disease therefore had limited targeted treatment options after progression on their primary therapy.

Now, new studies and clinical trials have opened the door to effective treatments for this cohort of patients. The clinical trial DESTINY-Breast04, which was presented at ASCO 2022, led to the first FDA approval in August 2022 of a targeted therapy option for patients with HER2-low breast cancer subtypes, reclassifying this cohort as a new targetable subset in breast cancer.

DESTINY-Breast04 was the first randomized clinical trial to show that targeting HER2 provides clinically meaningful benefits for patients with HER2-low metastatic breast cancer, not only patients with HER2-positive disease. The phase 3 study enrolled about 557 patients with hormone receptor (HR)-negative or -positive breast cancer and centrally confirmed HER2-low expression who were previously treated with 1 or 2 prior lines of chemotherapy. Patients were randomized to receive either the antibody–drug conjugate trastuzumab deruxtecan or physician’s choice of standard chemotherapy. The risk of disease progression was about 50% lower and the risk of death was about 36% lower with trastuzumab deruxtecan compared with chemotherapy.¹

These impressive and practice-changing results opened the door to a new treatment option for a substantial group of patients with HER2-low disease and significantly expanded the population of patients who can benefit from HER2-targeted therapy.

What molecular characteristics do you take into consideration to help determine whether patients are eligible for these targeted treatment options?

Dr. Abdou: As we said earlier, HER2 status should no longer be recorded as a binary result of either HER2-positive or HER2-negative. It is important to start routinely testing for the level of HER2 expression in the tumor. Obtaining these levels is done through commonly used immunohistochemical (IHC) assays that allow direct visualization of the HER2 protein. Breast tumors considered to be HER2-low are classified as IHC1+ or as IHC2+ with in situ hybridization or FISH-negative status.

HER2-low breast cancer consists of a heterogeneous group of breast cancers, most of which are HR-positive tumors, whereas about 20% are HR-negative tumors. While these tumors may have distinct molecular profiles leading to clinicopathological and prognostic differences within these groups—HR-positive tumors represent more luminal subtypes and HR-negative tumors tend to be predominantly basal-like subtypes—these distinctions do not necessarily affect patient eligibility for targeted therapy. The benefit of trastuzumab deruxtecan was seen in both subgroups, although the HR-positive population was much more well represented in the DESTINY-Breast04 study.

Other than the HER2 expression status, I also take into consideration the presence of clinical comorbidities, particularly pulmonary comorbidities or prior lung injuries. Trastuzumab deruxtecan can cause a potentially serious type of lung toxicity called interstitial lung disease (ILD). In DESTINY-Breast04, ILD developed in about 12% of patients in the trastuzumab deruxtecan group, with 3 deaths as a result.

Therefore, it’s important for us to carefully select these patients and closely monitor them while they’re on treatment.

What is next in the treatment of HER2-low breast cancer, and what would you like to see in the future?

Dr. Abdou: The exciting new field of HER2-low breast cancer has really opened the door to novel studies and clinical trials, several of which are exploring the role of antibody–drug conjugates in patients with metastatic HER2-low disease and others that are studying early-stage HER2-low breast cancer. In early-stage HER2-low breast cancer, we may potentially see an even greater benefit with these drugs because the disease has not yet developed resistance to therapy. Other studies are examining the role of combination therapy in metastatic breast cancer, such as antibody–drug conjugates in combination with immunotherapy and other targeted agents. I look forward to results from those studies.

Also, importantly, as we start using these therapies more widely, I would like to see more accurate and sensitive ways of assessing the HER2 expression status. The current IHC assay, although widely available, fails to identify many women who have HER2 expression in their tumors. I think more sensitive tests may be able to identify even more women who can benefit from these targeted therapies.

Can you talk about the evolution and treatment of human epidermal growth factor receptor 2 (HER2)-low breast cancer?

Dr. Abdou: Until recently, HER2 status had been defined as a positive or negative result, but this convention has evolved, and now a newly defined population with low levels of HER2 expression has been identified. This HER2-low population accounts for about 55% of all breast cancers. Previously, low HER2 expression levels were considered HER2-negative in clinical practice because HER2-targeted therapies had been considered ineffective in this setting. Patients with HER2-low disease therefore had limited targeted treatment options after progression on their primary therapy.

Now, new studies and clinical trials have opened the door to effective treatments for this cohort of patients. The clinical trial DESTINY-Breast04, which was presented at ASCO 2022, led to the first FDA approval in August 2022 of a targeted therapy option for patients with HER2-low breast cancer subtypes, reclassifying this cohort as a new targetable subset in breast cancer.

DESTINY-Breast04 was the first randomized clinical trial to show that targeting HER2 provides clinically meaningful benefits for patients with HER2-low metastatic breast cancer, not only patients with HER2-positive disease. The phase 3 study enrolled about 557 patients with hormone receptor (HR)-negative or -positive breast cancer and centrally confirmed HER2-low expression who were previously treated with 1 or 2 prior lines of chemotherapy. Patients were randomized to receive either the antibody–drug conjugate trastuzumab deruxtecan or physician’s choice of standard chemotherapy. The risk of disease progression was about 50% lower and the risk of death was about 36% lower with trastuzumab deruxtecan compared with chemotherapy.¹

These impressive and practice-changing results opened the door to a new treatment option for a substantial group of patients with HER2-low disease and significantly expanded the population of patients who can benefit from HER2-targeted therapy.

What molecular characteristics do you take into consideration to help determine whether patients are eligible for these targeted treatment options?

Dr. Abdou: As we said earlier, HER2 status should no longer be recorded as a binary result of either HER2-positive or HER2-negative. It is important to start routinely testing for the level of HER2 expression in the tumor. Obtaining these levels is done through commonly used immunohistochemical (IHC) assays that allow direct visualization of the HER2 protein. Breast tumors considered to be HER2-low are classified as IHC1+ or as IHC2+ with in situ hybridization or FISH-negative status.

HER2-low breast cancer consists of a heterogeneous group of breast cancers, most of which are HR-positive tumors, whereas about 20% are HR-negative tumors. While these tumors may have distinct molecular profiles leading to clinicopathological and prognostic differences within these groups—HR-positive tumors represent more luminal subtypes and HR-negative tumors tend to be predominantly basal-like subtypes—these distinctions do not necessarily affect patient eligibility for targeted therapy. The benefit of trastuzumab deruxtecan was seen in both subgroups, although the HR-positive population was much more well represented in the DESTINY-Breast04 study.

Other than the HER2 expression status, I also take into consideration the presence of clinical comorbidities, particularly pulmonary comorbidities or prior lung injuries. Trastuzumab deruxtecan can cause a potentially serious type of lung toxicity called interstitial lung disease (ILD). In DESTINY-Breast04, ILD developed in about 12% of patients in the trastuzumab deruxtecan group, with 3 deaths as a result.

Therefore, it’s important for us to carefully select these patients and closely monitor them while they’re on treatment.

What is next in the treatment of HER2-low breast cancer, and what would you like to see in the future?

Dr. Abdou: The exciting new field of HER2-low breast cancer has really opened the door to novel studies and clinical trials, several of which are exploring the role of antibody–drug conjugates in patients with metastatic HER2-low disease and others that are studying early-stage HER2-low breast cancer. In early-stage HER2-low breast cancer, we may potentially see an even greater benefit with these drugs because the disease has not yet developed resistance to therapy. Other studies are examining the role of combination therapy in metastatic breast cancer, such as antibody–drug conjugates in combination with immunotherapy and other targeted agents. I look forward to results from those studies.

Also, importantly, as we start using these therapies more widely, I would like to see more accurate and sensitive ways of assessing the HER2 expression status. The current IHC assay, although widely available, fails to identify many women who have HER2 expression in their tumors. I think more sensitive tests may be able to identify even more women who can benefit from these targeted therapies.

Correct answer: B. Selenium exposure. 
 
Rationale 
Helicobacter pylori infection is by far the most important risk factor for gastric cancer worldwide. Less common risk factors for gastric cancer include Lynch syndrome, Peutz-Jeghers syndrome, Menetrier's disease, and germline mutations in the CDH gene (encoding E-cadherin). However, there is some evidence that selenium, as well as high consumption of fruits and vegetables, may have protective effects against gastric cancer.  
 
References  
de Martel C et al. Gastroenterol Clin North Am. 2013 Jun;42(2):219-40.  
Giardiello FM et al. N Engl J Med. 1987 Jun 11;316(24):1511-4.  
Qiao YL et al. J Natl Cancer Inst. 2009 Apr 1;101(7):507-18. 

Correct answer: B. Selenium exposure. 
 
Rationale 
Helicobacter pylori infection is by far the most important risk factor for gastric cancer worldwide. Less common risk factors for gastric cancer include Lynch syndrome, Peutz-Jeghers syndrome, Menetrier's disease, and germline mutations in the CDH gene (encoding E-cadherin). However, there is some evidence that selenium, as well as high consumption of fruits and vegetables, may have protective effects against gastric cancer.  
 
References  
de Martel C et al. Gastroenterol Clin North Am. 2013 Jun;42(2):219-40.  
Giardiello FM et al. N Engl J Med. 1987 Jun 11;316(24):1511-4.  
Qiao YL et al. J Natl Cancer Inst. 2009 Apr 1;101(7):507-18. 

Correct answer: B. Selenium exposure. 
 
Rationale 
Helicobacter pylori infection is by far the most important risk factor for gastric cancer worldwide. Less common risk factors for gastric cancer include Lynch syndrome, Peutz-Jeghers syndrome, Menetrier's disease, and germline mutations in the CDH gene (encoding E-cadherin). However, there is some evidence that selenium, as well as high consumption of fruits and vegetables, may have protective effects against gastric cancer.  
 
References  
de Martel C et al. Gastroenterol Clin North Am. 2013 Jun;42(2):219-40.  
Giardiello FM et al. N Engl J Med. 1987 Jun 11;316(24):1511-4.  
Qiao YL et al. J Natl Cancer Inst. 2009 Apr 1;101(7):507-18. 

Correct answer: E. Cervical dysplasia. 
 
Rationale  
In a nationwide cohort study, women with Crohn's disease and ulcerative colitis were found to have an increased risk of cervical dysplasia. Patients with ulcerative colitis had increased risks of low- and high-grade squamous intraepithelial lesions, whereas patients with Crohn's disease also had increased risks of cervical cancer. Age-appropriate screening with pap smears is important for women diagnosed with inflammatory bowel disease regardless of treatment type.  
 
Reference  
Rungoe et al. Clin Gastroenterol Hepatol. 2015 Apr;13(4):693-700.e1.

Correct answer: E. Cervical dysplasia. 
 
Rationale  
In a nationwide cohort study, women with Crohn's disease and ulcerative colitis were found to have an increased risk of cervical dysplasia. Patients with ulcerative colitis had increased risks of low- and high-grade squamous intraepithelial lesions, whereas patients with Crohn's disease also had increased risks of cervical cancer. Age-appropriate screening with pap smears is important for women diagnosed with inflammatory bowel disease regardless of treatment type.  
 
Reference  
Rungoe et al. Clin Gastroenterol Hepatol. 2015 Apr;13(4):693-700.e1.

Correct answer: E. Cervical dysplasia. 
 
Rationale  
In a nationwide cohort study, women with Crohn's disease and ulcerative colitis were found to have an increased risk of cervical dysplasia. Patients with ulcerative colitis had increased risks of low- and high-grade squamous intraepithelial lesions, whereas patients with Crohn's disease also had increased risks of cervical cancer. Age-appropriate screening with pap smears is important for women diagnosed with inflammatory bowel disease regardless of treatment type.  
 
Reference  
Rungoe et al. Clin Gastroenterol Hepatol. 2015 Apr;13(4):693-700.e1.

Renal function should be considered when determining whether to pick ticagrelor-aspirin or clopidogrel-aspirin as the antiplatelet therapy for patients with minor stroke, according to new research.

The study, which was conducted in 202 centers in China and published in Annals of Internal Medicine, indicates that when patients had normal kidney function, ticagrelor-aspirin, compared with clopidogrel-aspirin, substantially reduced the risk for recurrent stroke within 90 days of follow-up.

However, this effect was not seen in patients with mildly, moderately or severely decreased kidney function.

Rates of severe or moderate bleeding did not differ substantially between the two treatments.
 

Results gleaned from CHANCE-2 data

The researchers, led by Anxin Wang, PhD, from Capital Medical University in Beijing, conducted a post hoc analysis of the CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) trial.

The trial included 6,378 patients who carried cytochrome P450 2C19 (CYP2C19) loss-of-function (LOF) alleles who had experienced a minor stroke or transient ischemic attack.

Patients received either ticagrelor-aspirin or clopidogrel-aspirin, and their renal function was measured by estimated glomerular filtration rate. The authors listed as a limitation that no data were available on the presence of albuminuria or proteinuria.

The researchers investigated what effect renal function had on the efficacy and safety of the therapies.
 

Differences in the therapies

Clopidogrel-aspirin is often recommended for preventing stroke. It can reduce thrombotic risk in patients with impaired kidney function, the authors noted. Ticagrelor can provide greater, faster, and more consistent P2Y12 inhibition than clopidogrel, and evidence shows it is effective in preventing stroke recurrence, particularly in people carrying CYP2C19 LOF alleles.

When people have reduced kidney function, clopidogrel may be harder to clear than ticagrelor and there may be increased plasma concentrations, so function is important to consider when choosing an antiplatelet therapy, the authors wrote.
 

Choice may come down to cost

Geoffrey Barnes, MD, MSc, associate professor of vascular and cardiovascular medicine at University of Michigan Medicine in Ann Arbor, said in an interview that there has been momentum toward ticagrelor as a more potent choice than clopidogrel not just in populations with minor stroke but for people with MI and coronary stents.

He said he found the results surprising and was intrigued that this paper suggests looking more skeptically at ticagrelor when kidney function is impaired.

Still, the choice may also come down to what the patient can afford at the pharmacy, he said.

“The reality is many patients still get clopidogrel either because that’s what their physicians have been prescribing for well over a decade or because of cost issues, and clopidogrel, for many patients, can be less expensive,” Dr. Barnes noted.

He said he would like to see more study in different populations as the prevalence of people carrying CYP2C19 allele differs by race and results might be different in a non-Asian population. That allele is thought to affect how clopidogrel is metabolized.
 

Study should spur more research

Nada El Husseini, MD, associate professor of neurology and Duke Telestroke Medical Director at Duke University Medical Center, Durham, N.C., said the study is hypothesis generating, but shouldn’t be thought of as the last word on the subject.

She pointed out some additional limitations of the study, including that it was a post hoc analysis. She explained that the question researchers asked in this study – about effect of kidney function on the safety and efficacy of the therapies – was not the focus of the original CHANCE-2 study, and, as such, the post hoc study may have been underpowered to answer the renal function question.

The authors acknowledged that limitation, noting that “the proportion of patients with severely decreased renal function was low.”

Among 6,378 patients, 4,050 (63.5%) had normal kidney function, 2,010 (31.5%) had mildly decreased function, and 318 (5.0%) had moderately to severely decreased function.

The study was funded by the Ministry of Science and Technology of the People’s Republic of China, the Beijing Municipal Science and Technology Commission, the Chinese Stroke Association, the National Science and Technology Major Project and the Beijing Municipal Administration of Hospitals Incubating Program). Salubris Pharmaceuticals contributed ticagrelor and, clopidogrel at no cost and with no restrictions. Dr. Wang reported no relevant financial relationships. Dr. Barnes and Dr. El Husseini reported no relevant financial relationships.

Renal function should be considered when determining whether to pick ticagrelor-aspirin or clopidogrel-aspirin as the antiplatelet therapy for patients with minor stroke, according to new research.

The study, which was conducted in 202 centers in China and published in Annals of Internal Medicine, indicates that when patients had normal kidney function, ticagrelor-aspirin, compared with clopidogrel-aspirin, substantially reduced the risk for recurrent stroke within 90 days of follow-up.

However, this effect was not seen in patients with mildly, moderately or severely decreased kidney function.

Rates of severe or moderate bleeding did not differ substantially between the two treatments.
 

Results gleaned from CHANCE-2 data

The researchers, led by Anxin Wang, PhD, from Capital Medical University in Beijing, conducted a post hoc analysis of the CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) trial.

The trial included 6,378 patients who carried cytochrome P450 2C19 (CYP2C19) loss-of-function (LOF) alleles who had experienced a minor stroke or transient ischemic attack.

Patients received either ticagrelor-aspirin or clopidogrel-aspirin, and their renal function was measured by estimated glomerular filtration rate. The authors listed as a limitation that no data were available on the presence of albuminuria or proteinuria.

The researchers investigated what effect renal function had on the efficacy and safety of the therapies.
 

Differences in the therapies

Clopidogrel-aspirin is often recommended for preventing stroke. It can reduce thrombotic risk in patients with impaired kidney function, the authors noted. Ticagrelor can provide greater, faster, and more consistent P2Y12 inhibition than clopidogrel, and evidence shows it is effective in preventing stroke recurrence, particularly in people carrying CYP2C19 LOF alleles.

When people have reduced kidney function, clopidogrel may be harder to clear than ticagrelor and there may be increased plasma concentrations, so function is important to consider when choosing an antiplatelet therapy, the authors wrote.
 

Choice may come down to cost

Geoffrey Barnes, MD, MSc, associate professor of vascular and cardiovascular medicine at University of Michigan Medicine in Ann Arbor, said in an interview that there has been momentum toward ticagrelor as a more potent choice than clopidogrel not just in populations with minor stroke but for people with MI and coronary stents.

He said he found the results surprising and was intrigued that this paper suggests looking more skeptically at ticagrelor when kidney function is impaired.

Still, the choice may also come down to what the patient can afford at the pharmacy, he said.

“The reality is many patients still get clopidogrel either because that’s what their physicians have been prescribing for well over a decade or because of cost issues, and clopidogrel, for many patients, can be less expensive,” Dr. Barnes noted.

He said he would like to see more study in different populations as the prevalence of people carrying CYP2C19 allele differs by race and results might be different in a non-Asian population. That allele is thought to affect how clopidogrel is metabolized.
 

Study should spur more research

Nada El Husseini, MD, associate professor of neurology and Duke Telestroke Medical Director at Duke University Medical Center, Durham, N.C., said the study is hypothesis generating, but shouldn’t be thought of as the last word on the subject.

She pointed out some additional limitations of the study, including that it was a post hoc analysis. She explained that the question researchers asked in this study – about effect of kidney function on the safety and efficacy of the therapies – was not the focus of the original CHANCE-2 study, and, as such, the post hoc study may have been underpowered to answer the renal function question.

The authors acknowledged that limitation, noting that “the proportion of patients with severely decreased renal function was low.”

Among 6,378 patients, 4,050 (63.5%) had normal kidney function, 2,010 (31.5%) had mildly decreased function, and 318 (5.0%) had moderately to severely decreased function.

The study was funded by the Ministry of Science and Technology of the People’s Republic of China, the Beijing Municipal Science and Technology Commission, the Chinese Stroke Association, the National Science and Technology Major Project and the Beijing Municipal Administration of Hospitals Incubating Program). Salubris Pharmaceuticals contributed ticagrelor and, clopidogrel at no cost and with no restrictions. Dr. Wang reported no relevant financial relationships. Dr. Barnes and Dr. El Husseini reported no relevant financial relationships.

Renal function should be considered when determining whether to pick ticagrelor-aspirin or clopidogrel-aspirin as the antiplatelet therapy for patients with minor stroke, according to new research.

The study, which was conducted in 202 centers in China and published in Annals of Internal Medicine, indicates that when patients had normal kidney function, ticagrelor-aspirin, compared with clopidogrel-aspirin, substantially reduced the risk for recurrent stroke within 90 days of follow-up.

However, this effect was not seen in patients with mildly, moderately or severely decreased kidney function.

Rates of severe or moderate bleeding did not differ substantially between the two treatments.
 

Results gleaned from CHANCE-2 data

The researchers, led by Anxin Wang, PhD, from Capital Medical University in Beijing, conducted a post hoc analysis of the CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) trial.

The trial included 6,378 patients who carried cytochrome P450 2C19 (CYP2C19) loss-of-function (LOF) alleles who had experienced a minor stroke or transient ischemic attack.

Patients received either ticagrelor-aspirin or clopidogrel-aspirin, and their renal function was measured by estimated glomerular filtration rate. The authors listed as a limitation that no data were available on the presence of albuminuria or proteinuria.

The researchers investigated what effect renal function had on the efficacy and safety of the therapies.
 

Differences in the therapies

Clopidogrel-aspirin is often recommended for preventing stroke. It can reduce thrombotic risk in patients with impaired kidney function, the authors noted. Ticagrelor can provide greater, faster, and more consistent P2Y12 inhibition than clopidogrel, and evidence shows it is effective in preventing stroke recurrence, particularly in people carrying CYP2C19 LOF alleles.

When people have reduced kidney function, clopidogrel may be harder to clear than ticagrelor and there may be increased plasma concentrations, so function is important to consider when choosing an antiplatelet therapy, the authors wrote.
 

Choice may come down to cost

Geoffrey Barnes, MD, MSc, associate professor of vascular and cardiovascular medicine at University of Michigan Medicine in Ann Arbor, said in an interview that there has been momentum toward ticagrelor as a more potent choice than clopidogrel not just in populations with minor stroke but for people with MI and coronary stents.

He said he found the results surprising and was intrigued that this paper suggests looking more skeptically at ticagrelor when kidney function is impaired.

Still, the choice may also come down to what the patient can afford at the pharmacy, he said.

“The reality is many patients still get clopidogrel either because that’s what their physicians have been prescribing for well over a decade or because of cost issues, and clopidogrel, for many patients, can be less expensive,” Dr. Barnes noted.

He said he would like to see more study in different populations as the prevalence of people carrying CYP2C19 allele differs by race and results might be different in a non-Asian population. That allele is thought to affect how clopidogrel is metabolized.
 

Study should spur more research

Nada El Husseini, MD, associate professor of neurology and Duke Telestroke Medical Director at Duke University Medical Center, Durham, N.C., said the study is hypothesis generating, but shouldn’t be thought of as the last word on the subject.

She pointed out some additional limitations of the study, including that it was a post hoc analysis. She explained that the question researchers asked in this study – about effect of kidney function on the safety and efficacy of the therapies – was not the focus of the original CHANCE-2 study, and, as such, the post hoc study may have been underpowered to answer the renal function question.

The authors acknowledged that limitation, noting that “the proportion of patients with severely decreased renal function was low.”

Among 6,378 patients, 4,050 (63.5%) had normal kidney function, 2,010 (31.5%) had mildly decreased function, and 318 (5.0%) had moderately to severely decreased function.

The study was funded by the Ministry of Science and Technology of the People’s Republic of China, the Beijing Municipal Science and Technology Commission, the Chinese Stroke Association, the National Science and Technology Major Project and the Beijing Municipal Administration of Hospitals Incubating Program). Salubris Pharmaceuticals contributed ticagrelor and, clopidogrel at no cost and with no restrictions. Dr. Wang reported no relevant financial relationships. Dr. Barnes and Dr. El Husseini reported no relevant financial relationships.

The effectiveness of up to three doses of COVID-19 vaccine was moderate overall and significantly lower among individuals with immunocompromising conditions, compared with the general population during the period of Omicron dominance, according to an analysis of data from more than 34,000 hospitalizations.

Previous studies have suggested lower COVID-19 vaccine effectiveness among immunocompromised individuals, compared with healthy individuals from the general population, but data from the period in which Omicron subvariants have been dominant are limited, wrote Amadea Britton, MD, of the Centers for Disease Control and Prevention’s COVID-19 Emergency Response Team, and colleagues.

The CDC currently recommends an expanded primary vaccine series of three doses of an mRNA vaccine, and the Advisory Committee on Immunization Practices has recommended a fourth dose with the new bivalent booster that contains elements of the Omicron variant, the researchers noted.

In a study published in the CDC’s Morbidity and Mortality Weekly Report, the researchers identified 34,220 adults with immunocompromising conditions who were hospitalized for COVID-19–like illness between Dec. 16, 2021, and Aug. 20, 2022. These conditions included solid malignancy (40.5%), hematologic malignancy (14.6%), rheumatologic or inflammatory disorder (24.4%), other intrinsic immune condition or immunodeficiency (38.5%), or organ or stem cell transplant (8.6%). They used data from the CDC’s VISION Network, a multistate database. The data include spring and summer 2022, when the BA.4 and BA.5 Omicron subvariants dominated other strains, and adults with immunocompromising conditions were eligible for a total of four vaccine doses (two primary doses and two boosters). The median age of the study population was 69 years, and 25.7%, 41.7%, and 7.0% had received two, three, and four doses, respectively, of COVID-19 vaccine.

Overall, vaccine effectiveness (VE) among immunocompromised patients was 34% after two vaccine doses, increasing to 71% during days 7-89 after a third dose, then declining to 41% 90 days or more after that dose.

During the full Omicron period, VE was 36% for 14 or more days after dose two, 69% for 7-89 days after dose three, and 44% for 90 or more days after dose three.

When VE was stratified by sublineage period, VE was higher 7 or more days after dose three during the predominance of BA.1 (67%), compared with VE during the dominant periods of BA.2/BA.2.12.1 (32%) and BA.4/BA.5 (35%).

In the later periods when Omicron BA.2/BA.2.12.1 and BA.4/BA.5 variants dominated, and individuals who had received three doses of vaccine were eligible for a fourth, VE against these variants was 32% 90 or more days after dose three and 43% 7 or more days after dose four.

VE was lowest among individuals with potentially more severe immunocompromising conditions, notably solid organ or stem cell transplants, the researchers wrote in their discussion.

The study findings were limited by several factors including the use of ICD-9 and -10 discharge diagnosis codes for immunocompromising conditions, potential confounding in VE models, lack of data on outpatient treatments such as nirmatelvir/ritonavir (Paxlovid), and lack of COVID-19 genomic sequencing data that may have affected which sublineage was identified, the researchers noted.

However, “this study confirms that even with boosters, immunocompromised adults, because of their weakened immune systems, are still at high risk of moderate to severe COVID,” said coauthor Brian Dixon, PhD, of the Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, in a press release about the study.

“Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent vaccine booster doses that target recently circulating Omicron sublineages, in line with ACIP [Advisory Committee on Immunization Practices] recommendations,” the researchers concluded in the study.

The study was funded by the CDC. The researchers had no financial conflicts to disclose. The VISION Network is a collaboration between the CDC, the Regenstrief Institute, and seven health care systems across the United States: Columbia University Irving Medical Center (New York), HealthPartners (Wisconsin), Intermountain Healthcare (Utah), Kaiser Permanente Northern California, Kaiser Permanente Northwest (Washington State), the University of Colorado, and Paso Del Norte Health Information Exchange (Texas).

The effectiveness of up to three doses of COVID-19 vaccine was moderate overall and significantly lower among individuals with immunocompromising conditions, compared with the general population during the period of Omicron dominance, according to an analysis of data from more than 34,000 hospitalizations.

Previous studies have suggested lower COVID-19 vaccine effectiveness among immunocompromised individuals, compared with healthy individuals from the general population, but data from the period in which Omicron subvariants have been dominant are limited, wrote Amadea Britton, MD, of the Centers for Disease Control and Prevention’s COVID-19 Emergency Response Team, and colleagues.

The CDC currently recommends an expanded primary vaccine series of three doses of an mRNA vaccine, and the Advisory Committee on Immunization Practices has recommended a fourth dose with the new bivalent booster that contains elements of the Omicron variant, the researchers noted.

In a study published in the CDC’s Morbidity and Mortality Weekly Report, the researchers identified 34,220 adults with immunocompromising conditions who were hospitalized for COVID-19–like illness between Dec. 16, 2021, and Aug. 20, 2022. These conditions included solid malignancy (40.5%), hematologic malignancy (14.6%), rheumatologic or inflammatory disorder (24.4%), other intrinsic immune condition or immunodeficiency (38.5%), or organ or stem cell transplant (8.6%). They used data from the CDC’s VISION Network, a multistate database. The data include spring and summer 2022, when the BA.4 and BA.5 Omicron subvariants dominated other strains, and adults with immunocompromising conditions were eligible for a total of four vaccine doses (two primary doses and two boosters). The median age of the study population was 69 years, and 25.7%, 41.7%, and 7.0% had received two, three, and four doses, respectively, of COVID-19 vaccine.

Overall, vaccine effectiveness (VE) among immunocompromised patients was 34% after two vaccine doses, increasing to 71% during days 7-89 after a third dose, then declining to 41% 90 days or more after that dose.

During the full Omicron period, VE was 36% for 14 or more days after dose two, 69% for 7-89 days after dose three, and 44% for 90 or more days after dose three.

When VE was stratified by sublineage period, VE was higher 7 or more days after dose three during the predominance of BA.1 (67%), compared with VE during the dominant periods of BA.2/BA.2.12.1 (32%) and BA.4/BA.5 (35%).

In the later periods when Omicron BA.2/BA.2.12.1 and BA.4/BA.5 variants dominated, and individuals who had received three doses of vaccine were eligible for a fourth, VE against these variants was 32% 90 or more days after dose three and 43% 7 or more days after dose four.

VE was lowest among individuals with potentially more severe immunocompromising conditions, notably solid organ or stem cell transplants, the researchers wrote in their discussion.

The study findings were limited by several factors including the use of ICD-9 and -10 discharge diagnosis codes for immunocompromising conditions, potential confounding in VE models, lack of data on outpatient treatments such as nirmatelvir/ritonavir (Paxlovid), and lack of COVID-19 genomic sequencing data that may have affected which sublineage was identified, the researchers noted.

However, “this study confirms that even with boosters, immunocompromised adults, because of their weakened immune systems, are still at high risk of moderate to severe COVID,” said coauthor Brian Dixon, PhD, of the Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, in a press release about the study.

“Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent vaccine booster doses that target recently circulating Omicron sublineages, in line with ACIP [Advisory Committee on Immunization Practices] recommendations,” the researchers concluded in the study.

The study was funded by the CDC. The researchers had no financial conflicts to disclose. The VISION Network is a collaboration between the CDC, the Regenstrief Institute, and seven health care systems across the United States: Columbia University Irving Medical Center (New York), HealthPartners (Wisconsin), Intermountain Healthcare (Utah), Kaiser Permanente Northern California, Kaiser Permanente Northwest (Washington State), the University of Colorado, and Paso Del Norte Health Information Exchange (Texas).

The effectiveness of up to three doses of COVID-19 vaccine was moderate overall and significantly lower among individuals with immunocompromising conditions, compared with the general population during the period of Omicron dominance, according to an analysis of data from more than 34,000 hospitalizations.

Previous studies have suggested lower COVID-19 vaccine effectiveness among immunocompromised individuals, compared with healthy individuals from the general population, but data from the period in which Omicron subvariants have been dominant are limited, wrote Amadea Britton, MD, of the Centers for Disease Control and Prevention’s COVID-19 Emergency Response Team, and colleagues.

The CDC currently recommends an expanded primary vaccine series of three doses of an mRNA vaccine, and the Advisory Committee on Immunization Practices has recommended a fourth dose with the new bivalent booster that contains elements of the Omicron variant, the researchers noted.

In a study published in the CDC’s Morbidity and Mortality Weekly Report, the researchers identified 34,220 adults with immunocompromising conditions who were hospitalized for COVID-19–like illness between Dec. 16, 2021, and Aug. 20, 2022. These conditions included solid malignancy (40.5%), hematologic malignancy (14.6%), rheumatologic or inflammatory disorder (24.4%), other intrinsic immune condition or immunodeficiency (38.5%), or organ or stem cell transplant (8.6%). They used data from the CDC’s VISION Network, a multistate database. The data include spring and summer 2022, when the BA.4 and BA.5 Omicron subvariants dominated other strains, and adults with immunocompromising conditions were eligible for a total of four vaccine doses (two primary doses and two boosters). The median age of the study population was 69 years, and 25.7%, 41.7%, and 7.0% had received two, three, and four doses, respectively, of COVID-19 vaccine.

Overall, vaccine effectiveness (VE) among immunocompromised patients was 34% after two vaccine doses, increasing to 71% during days 7-89 after a third dose, then declining to 41% 90 days or more after that dose.

During the full Omicron period, VE was 36% for 14 or more days after dose two, 69% for 7-89 days after dose three, and 44% for 90 or more days after dose three.

When VE was stratified by sublineage period, VE was higher 7 or more days after dose three during the predominance of BA.1 (67%), compared with VE during the dominant periods of BA.2/BA.2.12.1 (32%) and BA.4/BA.5 (35%).

In the later periods when Omicron BA.2/BA.2.12.1 and BA.4/BA.5 variants dominated, and individuals who had received three doses of vaccine were eligible for a fourth, VE against these variants was 32% 90 or more days after dose three and 43% 7 or more days after dose four.

VE was lowest among individuals with potentially more severe immunocompromising conditions, notably solid organ or stem cell transplants, the researchers wrote in their discussion.

The study findings were limited by several factors including the use of ICD-9 and -10 discharge diagnosis codes for immunocompromising conditions, potential confounding in VE models, lack of data on outpatient treatments such as nirmatelvir/ritonavir (Paxlovid), and lack of COVID-19 genomic sequencing data that may have affected which sublineage was identified, the researchers noted.

However, “this study confirms that even with boosters, immunocompromised adults, because of their weakened immune systems, are still at high risk of moderate to severe COVID,” said coauthor Brian Dixon, PhD, of the Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, in a press release about the study.

“Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent vaccine booster doses that target recently circulating Omicron sublineages, in line with ACIP [Advisory Committee on Immunization Practices] recommendations,” the researchers concluded in the study.

The study was funded by the CDC. The researchers had no financial conflicts to disclose. The VISION Network is a collaboration between the CDC, the Regenstrief Institute, and seven health care systems across the United States: Columbia University Irving Medical Center (New York), HealthPartners (Wisconsin), Intermountain Healthcare (Utah), Kaiser Permanente Northern California, Kaiser Permanente Northwest (Washington State), the University of Colorado, and Paso Del Norte Health Information Exchange (Texas).

DENVER – The top three social media platforms used by patients who seek aesthetic medical treatments in the United States are Facebook, Instagram, and YouTube. However, in a recent survey, when asked if an aesthetic medical provider’s social media presence positively affects their desire to see that provider, 48% of patients were neutral or had no opinion, while 41% indicated yes.

Gerd Altmann/pixabay

Those are key findings from the survey, which aimed to evaluate the social media preferences and perceptions of patients who undergo aesthetic procedures.

“Aesthetic providers have firmly established a presence on social media,” Morgan Murphrey, MD, said at the annual meeting of the American Society for Dermatologic Surgery, where she presented the results. “According to the dermatology literature, somewhere between 25% and 50% of patients are looking up aesthetic providers on social media before they even see them in the clinic. This raises the question: How do patients perceive aesthetic providers that are on social media, and what do they want to see on their professional accounts?”

To find out, Dr. Murphrey, chief dermatology resident at the University of California, Davis, and Sabrina Fabi, MD, a San Diego–based cosmetic dermatologist, used Survey Monkey to randomly survey 2,063 individuals in the United States. They used descriptive statistics to analyze characteristics and responses of the study participants.

Of the 2,063 respondents, 651 (32%) indicated that they undergo medical aesthetic treatments including Botox injections, fillers, or laser procedures. More than half (56%) were women, 25% were 18-30 years old, 64% were 31-60 years old, and 11% were 61 years or older.

The three most common social media platforms they used were Facebook (70%), Instagram (65%), and YouTube (63%), followed by TikTok (45%) and Snapchat (29%). When the researchers stratified respondents by income level, individuals making $200,000 or more per year were statistically more likely to be on Instagram while those making less than $200,000 were more likely to be on Facebook and YouTube.

When asked if their aesthetic medical provider’s social media presence positively impacts their desire to see them as a patient, 48% of respondent were neutral or had no opinion, while 41% answered yes. “Only 2% felt strongly about this if the provider was on a specific social media platform, while 9% of respondents preferred that their provider not be on social media,” Dr. Murphrey added.

When asked if the number of social media followers influences their perception of an aesthetic provider as an expert, 43% of respondents answered no while 57% answered yes. “Once you get to about 20,000 followers, there seems to be somewhat of a law of diminishing returns in the number of followers,” she said. However, 55% indicated that they prefer to see a provider with a social media account that is verified with a blue check mark.

As for content published, 70% of respondents found it very important (36%) or important (34%) that a provider show before-and-after photos on their social media pages, while 67% said that they favor viewing personal content such as posts about the provider’s family and hobbies.

“This study summarizes to us that there is really low risk to creating a social media account; it’s something to think about,” Dr. Murphrey said. “Only 9% of respondents really didn’t want aesthetic providers to be on social media, but when we stratified our results, those individuals were less likely to be on social media themselves.”

Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., and was asked to comment on the results, characterized the findings as important, “as the role of social media (especially visually based platforms like Instagram) will only continue to grow in our dermatologic and aesthetic practices.” Several studies have displayed a trend of plastic surgeons and other subspecialities outnumbering dermatologists within the aesthetic realm of social media, she noted. “As our patients increasingly seek out health care information and advice through these platforms, studies like Dr. Murphrey’s and Dr. Fabi’s are helpful in allowing us to better understand patient preferences and perspectives, in that we, as dermatologists, may be able to better aid their medical decisions in the future,” she added.

Neither the researchers nor Dr. Richey reported having relevant financial disclosures.

DENVER – The top three social media platforms used by patients who seek aesthetic medical treatments in the United States are Facebook, Instagram, and YouTube. However, in a recent survey, when asked if an aesthetic medical provider’s social media presence positively affects their desire to see that provider, 48% of patients were neutral or had no opinion, while 41% indicated yes.

Gerd Altmann/pixabay

Those are key findings from the survey, which aimed to evaluate the social media preferences and perceptions of patients who undergo aesthetic procedures.

“Aesthetic providers have firmly established a presence on social media,” Morgan Murphrey, MD, said at the annual meeting of the American Society for Dermatologic Surgery, where she presented the results. “According to the dermatology literature, somewhere between 25% and 50% of patients are looking up aesthetic providers on social media before they even see them in the clinic. This raises the question: How do patients perceive aesthetic providers that are on social media, and what do they want to see on their professional accounts?”

To find out, Dr. Murphrey, chief dermatology resident at the University of California, Davis, and Sabrina Fabi, MD, a San Diego–based cosmetic dermatologist, used Survey Monkey to randomly survey 2,063 individuals in the United States. They used descriptive statistics to analyze characteristics and responses of the study participants.

Of the 2,063 respondents, 651 (32%) indicated that they undergo medical aesthetic treatments including Botox injections, fillers, or laser procedures. More than half (56%) were women, 25% were 18-30 years old, 64% were 31-60 years old, and 11% were 61 years or older.

The three most common social media platforms they used were Facebook (70%), Instagram (65%), and YouTube (63%), followed by TikTok (45%) and Snapchat (29%). When the researchers stratified respondents by income level, individuals making $200,000 or more per year were statistically more likely to be on Instagram while those making less than $200,000 were more likely to be on Facebook and YouTube.

When asked if their aesthetic medical provider’s social media presence positively impacts their desire to see them as a patient, 48% of respondent were neutral or had no opinion, while 41% answered yes. “Only 2% felt strongly about this if the provider was on a specific social media platform, while 9% of respondents preferred that their provider not be on social media,” Dr. Murphrey added.

When asked if the number of social media followers influences their perception of an aesthetic provider as an expert, 43% of respondents answered no while 57% answered yes. “Once you get to about 20,000 followers, there seems to be somewhat of a law of diminishing returns in the number of followers,” she said. However, 55% indicated that they prefer to see a provider with a social media account that is verified with a blue check mark.

As for content published, 70% of respondents found it very important (36%) or important (34%) that a provider show before-and-after photos on their social media pages, while 67% said that they favor viewing personal content such as posts about the provider’s family and hobbies.

“This study summarizes to us that there is really low risk to creating a social media account; it’s something to think about,” Dr. Murphrey said. “Only 9% of respondents really didn’t want aesthetic providers to be on social media, but when we stratified our results, those individuals were less likely to be on social media themselves.”

Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., and was asked to comment on the results, characterized the findings as important, “as the role of social media (especially visually based platforms like Instagram) will only continue to grow in our dermatologic and aesthetic practices.” Several studies have displayed a trend of plastic surgeons and other subspecialities outnumbering dermatologists within the aesthetic realm of social media, she noted. “As our patients increasingly seek out health care information and advice through these platforms, studies like Dr. Murphrey’s and Dr. Fabi’s are helpful in allowing us to better understand patient preferences and perspectives, in that we, as dermatologists, may be able to better aid their medical decisions in the future,” she added.

Neither the researchers nor Dr. Richey reported having relevant financial disclosures.

DENVER – The top three social media platforms used by patients who seek aesthetic medical treatments in the United States are Facebook, Instagram, and YouTube. However, in a recent survey, when asked if an aesthetic medical provider’s social media presence positively affects their desire to see that provider, 48% of patients were neutral or had no opinion, while 41% indicated yes.

Gerd Altmann/pixabay

Those are key findings from the survey, which aimed to evaluate the social media preferences and perceptions of patients who undergo aesthetic procedures.

“Aesthetic providers have firmly established a presence on social media,” Morgan Murphrey, MD, said at the annual meeting of the American Society for Dermatologic Surgery, where she presented the results. “According to the dermatology literature, somewhere between 25% and 50% of patients are looking up aesthetic providers on social media before they even see them in the clinic. This raises the question: How do patients perceive aesthetic providers that are on social media, and what do they want to see on their professional accounts?”

To find out, Dr. Murphrey, chief dermatology resident at the University of California, Davis, and Sabrina Fabi, MD, a San Diego–based cosmetic dermatologist, used Survey Monkey to randomly survey 2,063 individuals in the United States. They used descriptive statistics to analyze characteristics and responses of the study participants.

Of the 2,063 respondents, 651 (32%) indicated that they undergo medical aesthetic treatments including Botox injections, fillers, or laser procedures. More than half (56%) were women, 25% were 18-30 years old, 64% were 31-60 years old, and 11% were 61 years or older.

The three most common social media platforms they used were Facebook (70%), Instagram (65%), and YouTube (63%), followed by TikTok (45%) and Snapchat (29%). When the researchers stratified respondents by income level, individuals making $200,000 or more per year were statistically more likely to be on Instagram while those making less than $200,000 were more likely to be on Facebook and YouTube.

When asked if their aesthetic medical provider’s social media presence positively impacts their desire to see them as a patient, 48% of respondent were neutral or had no opinion, while 41% answered yes. “Only 2% felt strongly about this if the provider was on a specific social media platform, while 9% of respondents preferred that their provider not be on social media,” Dr. Murphrey added.

When asked if the number of social media followers influences their perception of an aesthetic provider as an expert, 43% of respondents answered no while 57% answered yes. “Once you get to about 20,000 followers, there seems to be somewhat of a law of diminishing returns in the number of followers,” she said. However, 55% indicated that they prefer to see a provider with a social media account that is verified with a blue check mark.

As for content published, 70% of respondents found it very important (36%) or important (34%) that a provider show before-and-after photos on their social media pages, while 67% said that they favor viewing personal content such as posts about the provider’s family and hobbies.

“This study summarizes to us that there is really low risk to creating a social media account; it’s something to think about,” Dr. Murphrey said. “Only 9% of respondents really didn’t want aesthetic providers to be on social media, but when we stratified our results, those individuals were less likely to be on social media themselves.”

Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., and was asked to comment on the results, characterized the findings as important, “as the role of social media (especially visually based platforms like Instagram) will only continue to grow in our dermatologic and aesthetic practices.” Several studies have displayed a trend of plastic surgeons and other subspecialities outnumbering dermatologists within the aesthetic realm of social media, she noted. “As our patients increasingly seek out health care information and advice through these platforms, studies like Dr. Murphrey’s and Dr. Fabi’s are helpful in allowing us to better understand patient preferences and perspectives, in that we, as dermatologists, may be able to better aid their medical decisions in the future,” she added.

Neither the researchers nor Dr. Richey reported having relevant financial disclosures.

Acupuncture is a very popular treatment strategy in some areas of the world and is extensively applied in Chinese practice. Though this is a regularly applied treatment, a direct comparison with first-line antispasmodics has not been previously completed. The study by Shi and colleagues sought to compare the treatment of IBS using an adjusted indirect treatment comparison meta-analysis. This study proves that cimetropium was the most effective for relieving abdominal pain, whereas drotaverine, acupuncture, and pinaverium remained superior to the placebo. That being said, acupuncture was shown to be superior in relieving global IBS symptoms and caused fewer side effects than did antispasmodics. This shows that acupuncture may have a role in the treatment algorithm for IBS even outside of China, where it is used broadly.

The study by Formica and colleagues provides new insights on the etiology and pathogenesis of IBS. These insights include the positive correlation between disgust sensitivity and IBS quality of life (QOL) scores. The relationship between IBS and the emotional intensity of the experience of disgust is discussed throughout this study and more severe IBS-QOL scores were linked to those with high levels of disgust sensitivity. This study had gender limitations because of the low number of male participants, so these correlations were patterned mostly in female participants. 

Acupuncture is a very popular treatment strategy in some areas of the world and is extensively applied in Chinese practice. Though this is a regularly applied treatment, a direct comparison with first-line antispasmodics has not been previously completed. The study by Shi and colleagues sought to compare the treatment of IBS using an adjusted indirect treatment comparison meta-analysis. This study proves that cimetropium was the most effective for relieving abdominal pain, whereas drotaverine, acupuncture, and pinaverium remained superior to the placebo. That being said, acupuncture was shown to be superior in relieving global IBS symptoms and caused fewer side effects than did antispasmodics. This shows that acupuncture may have a role in the treatment algorithm for IBS even outside of China, where it is used broadly.

The study by Formica and colleagues provides new insights on the etiology and pathogenesis of IBS. These insights include the positive correlation between disgust sensitivity and IBS quality of life (QOL) scores. The relationship between IBS and the emotional intensity of the experience of disgust is discussed throughout this study and more severe IBS-QOL scores were linked to those with high levels of disgust sensitivity. This study had gender limitations because of the low number of male participants, so these correlations were patterned mostly in female participants. 

Acupuncture is a very popular treatment strategy in some areas of the world and is extensively applied in Chinese practice. Though this is a regularly applied treatment, a direct comparison with first-line antispasmodics has not been previously completed. The study by Shi and colleagues sought to compare the treatment of IBS using an adjusted indirect treatment comparison meta-analysis. This study proves that cimetropium was the most effective for relieving abdominal pain, whereas drotaverine, acupuncture, and pinaverium remained superior to the placebo. That being said, acupuncture was shown to be superior in relieving global IBS symptoms and caused fewer side effects than did antispasmodics. This shows that acupuncture may have a role in the treatment algorithm for IBS even outside of China, where it is used broadly.

The study by Formica and colleagues provides new insights on the etiology and pathogenesis of IBS. These insights include the positive correlation between disgust sensitivity and IBS quality of life (QOL) scores. The relationship between IBS and the emotional intensity of the experience of disgust is discussed throughout this study and more severe IBS-QOL scores were linked to those with high levels of disgust sensitivity. This study had gender limitations because of the low number of male participants, so these correlations were patterned mostly in female participants. 

When maternal-fetal medicine specialist Andra James, MD, MPH, trained as a midwife decades ago, women with sickle cell disease (SCD) were urged to never get pregnant. If they did, termination was considered the best option.

“If they did carry a pregnancy, the baby would not survive to the point of viability,” Dr. James, emeritus professor of obstetrics and gynecology at Duke University, Durham, N.C., recalled in an interview.

The fates of women with SCD have transformed dramatically since those grim days. In general, this blood disorder no longer robs patients of decades of life, and many women with SCD bear healthy children. But their pregnancies are still considered high risk with significant potential for health crises and death. Now, there’s a new complication: The overturning of Roe v. Wade.

Many states imposed tighter restrictions on abortions in the wake of the U.S. Supreme Court’s landmark Dobbs ruling, sparking worry among physicians that women with SCD won’t be able to get proper maternal care in some parts of the United States.

For example, women with SCD may be unable able to seek elective abortions in some states even if their pregnancies pose a danger to their lives. And abortion restrictions are imperiling access to a medication that’s used to treat miscarriages, which are more common in women with SCD.

“The situation with Dobbs is dire, and maternal health care is being compromised,” Johns Hopkins University pediatric hematologist Lydia Pecker, MD, who treats young people with SCD and studies its impact on pregnancy, said in an interview. “Women with sickle cell disease who are pregnant constitute an underserved and understudied population with special health care needs, and the Dobbs decision will only make providing their care even more difficult in many parts of the country.”

For her part, Dr. James described the risk to pregnant women with SCD this way: In the wake of the court ruling, “we increase the opportunity for them to lose their lives and for their babies to die.”
 

SCD’s impact on pregnancy

While physicians no longer advise women with SCD to avoid motherhood, pregnancy is still uniquely dangerous for them. “Most of them have babies and children who are thriving, but it’s not easy for them,” University of North Carolina at Chapel Hill hematologist and SCD specialist Jane Little, MD, said in an interview. And in some cases, she said, pregnancies “do not end well.”

For a 2022 report, Dr. Pecker and colleagues analyzed 2012-2018 data for 6,610 U.S. hospital admissions among women with SCD (87% of whom were Black). These women were more likely than were unaffected women to suffer severe maternal morbidity (odds ratio[OR], 4.63, 95% confidence interval [CI], 4.16-5.16, P < .001). Cerebrovascular event were especially more common in SCD (OR, 13.94, P < .001).

According to a 2019 report, pregnant women with SCD “are more likely to develop a host of complications, particularly hypertensive syndromes (such as preeclampsia), venous thromboembolism (VTE), preterm labor, and fetal loss. Newborns are more likely to have growth problems and prematurity.”

Although data are sparse, experts say it’s also clear that women with SCD face significantly higher risk of death in pregnancy compared to other women. In fact, the maternal mortality rate for females with SCD “is higher than for Black females without SCD, who already suffer from a higher mortality rate than White females during pregnancy and childbirth,” Andrea Roe, MD, MPH, assistant professor of obstetrics and gynecology at the Hospital of the University of Pennsylvania, Philadelphia, said in an interview.

Women with SCD also are more likely to have premature and stillborn births.

Some of the health challenges in pregnant women with SCD stem from the body’s inability to boost blood production in order to supply the placenta, said Dr. James, the Duke University emeritus professor. “Her bone marrow is already turning out red blood cells as fast as it can.”

In addition, she said, these women are more susceptible to infection, blood clots, and damage to the kidneys and lungs.

Still, in most cases of SCD in pregnancy, “we counsel a woman that we can get you safely through it,” Dr. James said. “But there is a subset of patients that will have organ damage from their sickle cell disease and should not become pregnant or stay pregnant if they become pregnant.”
 

Court ruling limits options in some states

The Dobbs ruling affects pregnant women with SCD in two ways: It allows states to restrict or ban abortion to greater extents than were possible over the last 50 years, and it has spawned further limitations on access to mifepristone, which is commonly used to treat early miscarriages.

In some cases, Dr. James said, abortions in this population are elective. “People with sickle cell disease are frequently in pain, they are frequently hospitalized. They may have suffered strokes or subclinical strokes or have some cognitive impairment, and they don’t have the mental and physical fortitude [to tolerate pregnancy and birth].”

In other cases, abortions are medically necessary to preserve the mother’s life. The American Society of Hematology highlighted the risks posed by SCD to maternal health in a June 24 statement that criticized the Dobbs ruling. “In some cases, denying women their right to terminate a pregnancy puts them at risk of serious illness or death,” wrote Jane N. Winter, MD, president of ASH and professor of medicine at Northwestern University, Chicago.

There do not appear to be any statistics about abortion rates among women with SCD in the United States or whether the rates are higher than in other groups.

As for miscarriages in SCD, an analysis of first pregnancies in California women with SCD from 1991 to 2016 found that about 16% were “incomplete,” mainly (59.3%) from miscarriage.

The Dobbs ruling allows states to further restrict the drug combination of mifepristone and misoprostol, which is used to trigger abortions and to treat early pregnancy loss. Access to mifepristone was already limited prior to the ruling due to tight regulation, and advocates say it’s now even harder to get.
 

What now? Physicians urge focus on contraception

As the ramifications of the Dobbs ruling sink in, SCD specialists are emphasizing the importance of providing gynecological and contraceptive care to help women with the condition avoid unwanted pregnancies. At the University of North Carolina, “we’re pretty aggressive about trying to give women the option to see a gynecologist to get the best care they can,” Dr. Little said. “We have a shared gynecology and sickle cell clinic because we really want women to be making the choice [to become pregnant] when they are ready because it’s a strain on their health and their lives.”

Dr. Pecker, the Johns Hopkins University pediatric hematologist, urged colleagues to partner with maternal-fetal medicine specialists so they can quickly get help for pregnant patients when needed. “That way they can get high-quality pregnancy care and help to end pregnancies that need to be ended.”

She recommended “highly effective” progesterone-based birth control as the best first-line contraceptive for women with SCD. And, she said, every woman of child-bearing age with SCD should be assessed annually for their intentions regarding pregnancy. As she put it, “there’s so much that we can do to reduce harms.”

Dr. Pecker disclosed financial relationships with the National Institutes of Health, American Society of Hematology, Doris Duke Charitable Foundation, the Mellon Foundation, Global Blood Therapeutics, and Novo Nordisk. Dr. Little disclosed financial relationships with Global Blood Therapeutics, Bluebird Bio, and Forma Therapeutics. Dr. Roe has no disclosures.

When maternal-fetal medicine specialist Andra James, MD, MPH, trained as a midwife decades ago, women with sickle cell disease (SCD) were urged to never get pregnant. If they did, termination was considered the best option.

“If they did carry a pregnancy, the baby would not survive to the point of viability,” Dr. James, emeritus professor of obstetrics and gynecology at Duke University, Durham, N.C., recalled in an interview.

The fates of women with SCD have transformed dramatically since those grim days. In general, this blood disorder no longer robs patients of decades of life, and many women with SCD bear healthy children. But their pregnancies are still considered high risk with significant potential for health crises and death. Now, there’s a new complication: The overturning of Roe v. Wade.

Many states imposed tighter restrictions on abortions in the wake of the U.S. Supreme Court’s landmark Dobbs ruling, sparking worry among physicians that women with SCD won’t be able to get proper maternal care in some parts of the United States.

For example, women with SCD may be unable able to seek elective abortions in some states even if their pregnancies pose a danger to their lives. And abortion restrictions are imperiling access to a medication that’s used to treat miscarriages, which are more common in women with SCD.

“The situation with Dobbs is dire, and maternal health care is being compromised,” Johns Hopkins University pediatric hematologist Lydia Pecker, MD, who treats young people with SCD and studies its impact on pregnancy, said in an interview. “Women with sickle cell disease who are pregnant constitute an underserved and understudied population with special health care needs, and the Dobbs decision will only make providing their care even more difficult in many parts of the country.”

For her part, Dr. James described the risk to pregnant women with SCD this way: In the wake of the court ruling, “we increase the opportunity for them to lose their lives and for their babies to die.”
 

SCD’s impact on pregnancy

While physicians no longer advise women with SCD to avoid motherhood, pregnancy is still uniquely dangerous for them. “Most of them have babies and children who are thriving, but it’s not easy for them,” University of North Carolina at Chapel Hill hematologist and SCD specialist Jane Little, MD, said in an interview. And in some cases, she said, pregnancies “do not end well.”

For a 2022 report, Dr. Pecker and colleagues analyzed 2012-2018 data for 6,610 U.S. hospital admissions among women with SCD (87% of whom were Black). These women were more likely than were unaffected women to suffer severe maternal morbidity (odds ratio[OR], 4.63, 95% confidence interval [CI], 4.16-5.16, P < .001). Cerebrovascular event were especially more common in SCD (OR, 13.94, P < .001).

According to a 2019 report, pregnant women with SCD “are more likely to develop a host of complications, particularly hypertensive syndromes (such as preeclampsia), venous thromboembolism (VTE), preterm labor, and fetal loss. Newborns are more likely to have growth problems and prematurity.”

Although data are sparse, experts say it’s also clear that women with SCD face significantly higher risk of death in pregnancy compared to other women. In fact, the maternal mortality rate for females with SCD “is higher than for Black females without SCD, who already suffer from a higher mortality rate than White females during pregnancy and childbirth,” Andrea Roe, MD, MPH, assistant professor of obstetrics and gynecology at the Hospital of the University of Pennsylvania, Philadelphia, said in an interview.

Women with SCD also are more likely to have premature and stillborn births.

Some of the health challenges in pregnant women with SCD stem from the body’s inability to boost blood production in order to supply the placenta, said Dr. James, the Duke University emeritus professor. “Her bone marrow is already turning out red blood cells as fast as it can.”

In addition, she said, these women are more susceptible to infection, blood clots, and damage to the kidneys and lungs.

Still, in most cases of SCD in pregnancy, “we counsel a woman that we can get you safely through it,” Dr. James said. “But there is a subset of patients that will have organ damage from their sickle cell disease and should not become pregnant or stay pregnant if they become pregnant.”
 

Court ruling limits options in some states

The Dobbs ruling affects pregnant women with SCD in two ways: It allows states to restrict or ban abortion to greater extents than were possible over the last 50 years, and it has spawned further limitations on access to mifepristone, which is commonly used to treat early miscarriages.

In some cases, Dr. James said, abortions in this population are elective. “People with sickle cell disease are frequently in pain, they are frequently hospitalized. They may have suffered strokes or subclinical strokes or have some cognitive impairment, and they don’t have the mental and physical fortitude [to tolerate pregnancy and birth].”

In other cases, abortions are medically necessary to preserve the mother’s life. The American Society of Hematology highlighted the risks posed by SCD to maternal health in a June 24 statement that criticized the Dobbs ruling. “In some cases, denying women their right to terminate a pregnancy puts them at risk of serious illness or death,” wrote Jane N. Winter, MD, president of ASH and professor of medicine at Northwestern University, Chicago.

There do not appear to be any statistics about abortion rates among women with SCD in the United States or whether the rates are higher than in other groups.

As for miscarriages in SCD, an analysis of first pregnancies in California women with SCD from 1991 to 2016 found that about 16% were “incomplete,” mainly (59.3%) from miscarriage.

The Dobbs ruling allows states to further restrict the drug combination of mifepristone and misoprostol, which is used to trigger abortions and to treat early pregnancy loss. Access to mifepristone was already limited prior to the ruling due to tight regulation, and advocates say it’s now even harder to get.
 

What now? Physicians urge focus on contraception

As the ramifications of the Dobbs ruling sink in, SCD specialists are emphasizing the importance of providing gynecological and contraceptive care to help women with the condition avoid unwanted pregnancies. At the University of North Carolina, “we’re pretty aggressive about trying to give women the option to see a gynecologist to get the best care they can,” Dr. Little said. “We have a shared gynecology and sickle cell clinic because we really want women to be making the choice [to become pregnant] when they are ready because it’s a strain on their health and their lives.”

Dr. Pecker, the Johns Hopkins University pediatric hematologist, urged colleagues to partner with maternal-fetal medicine specialists so they can quickly get help for pregnant patients when needed. “That way they can get high-quality pregnancy care and help to end pregnancies that need to be ended.”

She recommended “highly effective” progesterone-based birth control as the best first-line contraceptive for women with SCD. And, she said, every woman of child-bearing age with SCD should be assessed annually for their intentions regarding pregnancy. As she put it, “there’s so much that we can do to reduce harms.”

Dr. Pecker disclosed financial relationships with the National Institutes of Health, American Society of Hematology, Doris Duke Charitable Foundation, the Mellon Foundation, Global Blood Therapeutics, and Novo Nordisk. Dr. Little disclosed financial relationships with Global Blood Therapeutics, Bluebird Bio, and Forma Therapeutics. Dr. Roe has no disclosures.

When maternal-fetal medicine specialist Andra James, MD, MPH, trained as a midwife decades ago, women with sickle cell disease (SCD) were urged to never get pregnant. If they did, termination was considered the best option.

“If they did carry a pregnancy, the baby would not survive to the point of viability,” Dr. James, emeritus professor of obstetrics and gynecology at Duke University, Durham, N.C., recalled in an interview.

The fates of women with SCD have transformed dramatically since those grim days. In general, this blood disorder no longer robs patients of decades of life, and many women with SCD bear healthy children. But their pregnancies are still considered high risk with significant potential for health crises and death. Now, there’s a new complication: The overturning of Roe v. Wade.

Many states imposed tighter restrictions on abortions in the wake of the U.S. Supreme Court’s landmark Dobbs ruling, sparking worry among physicians that women with SCD won’t be able to get proper maternal care in some parts of the United States.

For example, women with SCD may be unable able to seek elective abortions in some states even if their pregnancies pose a danger to their lives. And abortion restrictions are imperiling access to a medication that’s used to treat miscarriages, which are more common in women with SCD.

“The situation with Dobbs is dire, and maternal health care is being compromised,” Johns Hopkins University pediatric hematologist Lydia Pecker, MD, who treats young people with SCD and studies its impact on pregnancy, said in an interview. “Women with sickle cell disease who are pregnant constitute an underserved and understudied population with special health care needs, and the Dobbs decision will only make providing their care even more difficult in many parts of the country.”

For her part, Dr. James described the risk to pregnant women with SCD this way: In the wake of the court ruling, “we increase the opportunity for them to lose their lives and for their babies to die.”
 

SCD’s impact on pregnancy

While physicians no longer advise women with SCD to avoid motherhood, pregnancy is still uniquely dangerous for them. “Most of them have babies and children who are thriving, but it’s not easy for them,” University of North Carolina at Chapel Hill hematologist and SCD specialist Jane Little, MD, said in an interview. And in some cases, she said, pregnancies “do not end well.”

For a 2022 report, Dr. Pecker and colleagues analyzed 2012-2018 data for 6,610 U.S. hospital admissions among women with SCD (87% of whom were Black). These women were more likely than were unaffected women to suffer severe maternal morbidity (odds ratio[OR], 4.63, 95% confidence interval [CI], 4.16-5.16, P < .001). Cerebrovascular event were especially more common in SCD (OR, 13.94, P < .001).

According to a 2019 report, pregnant women with SCD “are more likely to develop a host of complications, particularly hypertensive syndromes (such as preeclampsia), venous thromboembolism (VTE), preterm labor, and fetal loss. Newborns are more likely to have growth problems and prematurity.”

Although data are sparse, experts say it’s also clear that women with SCD face significantly higher risk of death in pregnancy compared to other women. In fact, the maternal mortality rate for females with SCD “is higher than for Black females without SCD, who already suffer from a higher mortality rate than White females during pregnancy and childbirth,” Andrea Roe, MD, MPH, assistant professor of obstetrics and gynecology at the Hospital of the University of Pennsylvania, Philadelphia, said in an interview.

Women with SCD also are more likely to have premature and stillborn births.

Some of the health challenges in pregnant women with SCD stem from the body’s inability to boost blood production in order to supply the placenta, said Dr. James, the Duke University emeritus professor. “Her bone marrow is already turning out red blood cells as fast as it can.”

In addition, she said, these women are more susceptible to infection, blood clots, and damage to the kidneys and lungs.

Still, in most cases of SCD in pregnancy, “we counsel a woman that we can get you safely through it,” Dr. James said. “But there is a subset of patients that will have organ damage from their sickle cell disease and should not become pregnant or stay pregnant if they become pregnant.”
 

Court ruling limits options in some states

The Dobbs ruling affects pregnant women with SCD in two ways: It allows states to restrict or ban abortion to greater extents than were possible over the last 50 years, and it has spawned further limitations on access to mifepristone, which is commonly used to treat early miscarriages.

In some cases, Dr. James said, abortions in this population are elective. “People with sickle cell disease are frequently in pain, they are frequently hospitalized. They may have suffered strokes or subclinical strokes or have some cognitive impairment, and they don’t have the mental and physical fortitude [to tolerate pregnancy and birth].”

In other cases, abortions are medically necessary to preserve the mother’s life. The American Society of Hematology highlighted the risks posed by SCD to maternal health in a June 24 statement that criticized the Dobbs ruling. “In some cases, denying women their right to terminate a pregnancy puts them at risk of serious illness or death,” wrote Jane N. Winter, MD, president of ASH and professor of medicine at Northwestern University, Chicago.

There do not appear to be any statistics about abortion rates among women with SCD in the United States or whether the rates are higher than in other groups.

As for miscarriages in SCD, an analysis of first pregnancies in California women with SCD from 1991 to 2016 found that about 16% were “incomplete,” mainly (59.3%) from miscarriage.

The Dobbs ruling allows states to further restrict the drug combination of mifepristone and misoprostol, which is used to trigger abortions and to treat early pregnancy loss. Access to mifepristone was already limited prior to the ruling due to tight regulation, and advocates say it’s now even harder to get.
 

What now? Physicians urge focus on contraception

As the ramifications of the Dobbs ruling sink in, SCD specialists are emphasizing the importance of providing gynecological and contraceptive care to help women with the condition avoid unwanted pregnancies. At the University of North Carolina, “we’re pretty aggressive about trying to give women the option to see a gynecologist to get the best care they can,” Dr. Little said. “We have a shared gynecology and sickle cell clinic because we really want women to be making the choice [to become pregnant] when they are ready because it’s a strain on their health and their lives.”

Dr. Pecker, the Johns Hopkins University pediatric hematologist, urged colleagues to partner with maternal-fetal medicine specialists so they can quickly get help for pregnant patients when needed. “That way they can get high-quality pregnancy care and help to end pregnancies that need to be ended.”

She recommended “highly effective” progesterone-based birth control as the best first-line contraceptive for women with SCD. And, she said, every woman of child-bearing age with SCD should be assessed annually for their intentions regarding pregnancy. As she put it, “there’s so much that we can do to reduce harms.”

Dr. Pecker disclosed financial relationships with the National Institutes of Health, American Society of Hematology, Doris Duke Charitable Foundation, the Mellon Foundation, Global Blood Therapeutics, and Novo Nordisk. Dr. Little disclosed financial relationships with Global Blood Therapeutics, Bluebird Bio, and Forma Therapeutics. Dr. Roe has no disclosures.