An article recently was published in The New York Times with a headline that read, “Dermatology Has a Problem With Skin Color.” ¹ The article featured interviews with many well-known dermatologists who are experts in skin of color (SOC), and their points followed a similar pattern—skin disease often looks different in patients with darker skin, and diagnoses often are delayed or missed altogether as a consequence of clinical uncertainty. The article included an interview with Jenna Lester, MD, who leads the SOC clinic at the University of California, San Francisco. In the article, she discussed how dermatologists are trained to recognize findings through pattern recognition. However, if we are only trained to diagnose dermatologic diseases on white skin, we will be unable to recognize diseases in patients with darker skin, leading to suboptimal patient care. ¹

Dermatology is a visual specialty, and residents go through thousands of photographs during residency training to distinguish different presentations and unique findings of a variety of skin diseases. Nevertheless, to Dr. Lester’s point, our learning is limited by the photographs and patients that we see.

Additionally, residents training in locations without diverse patient populations rely even more on images in educational resources to recognize clinical presentations in patients with darker skin. A study was published in Cutis earlier this year that surveyed dermatology residents about multiethnic training in residency.² It showed that residents training in less ethnically diverse areas such as the Midwest and Northwest were more likely to agree that dedicated multiethnic clinics and rotations are important to gain competence compared to residents training in more ethnically diverse regions such as the Southeast, Northeast, and Southwest. Most residents believed 1 to 5 hours per month of lectures covering conditions affecting SOC and/or multiethnic skin are needed to become competent.²

Limitations of Educational Resources

The images in dermatology educational resources do not reflect the diversity of our country’s population. A research letter recently was published in the Journal of the American Academy of Dermatology (JAAD) in which the authors assessed the number of images of dark skin—Fitzpatrick skin types V and VI—in dermatology educational resources.³ The authors analyzed images from 8 resources commonly used to study dermatology, including 6 printed texts and 2 online resources. Of the printed texts, Andrews’ Diseases of the Skin had the highest percentage of images of dark skin at 19.9%. Overall, VisualDx had the highest percentage of photographs of dark skin at 28.5%, while DermNet NZ had the lowest of all resources at only 2.8%.³

Similarly, a research letter published in the British Journal of Dermatology reviewed images in 2 standard dermatology textbooks.⁴ Although images of SOC made up 22% to 32% of the overall content, the number of images of sexually transmitted infections in SOC was disproportionate (47%–58%) compared to images of non–sexually transmitted infections (28%). The authors also stated that communities of color often have legacies of mistrust with the health care system, and diagnostic uncertainty can further impair the physician-patient relationship.⁴

The lack of diversity in clinical images and research was further exemplified by recent publications regarding the perniolike eruption associated with coronavirus disease 2019 (COVID-19), commonly referred to as COVID toes. A research letter was published in the British Journal of Dermatology earlier this year about the lack of images of SOC in publications about the cutaneous manifestations of COVID-19.⁵ At that time, there were zero published images of cutaneous COVID-19 manifestations in Fitzpatrick skin types V and VI, yet COVID-19 disproportionately affects Black individuals and other people of color.^5,6 A case series recently was published in JAAD Case Reports that included images of cutaneous COVID-19 findings in patients with Fitzpatrick skin types III through V.⁷ The authors noted that the findings were more subtle on darker skin as the erythema was harder to discern. The inability to identify the perniolike eruption ultimately can delay diagnosis.⁷

Resident Education

Over the past few months, I have reflected on my role as a dermatology resident and my dedication to antiracism in my personal and professional life. It is not a valid response or excuse to say that certain diagnoses are harder to make because of darker skin tone. It is our responsibility to do better for all patients. To that end, our educational resources should reflect our entire patient population.

I have been working with my coresident Annika Weinhammer, MD, on a quality improvement project to strengthen our educational curriculum at the University of Wisconsin regarding SOC. This project aims to enhance our skills as dermatologists in diagnosing and treating diseases in SOC. Moving forward, we have set an expectation that all didactic lectures must include images of SOC. Below, I have listed some of our initiatives along with recommendations for educational resources. There are multiple dermatology textbooks focused on SOC, including the following:

• Clinical Cases in Skin of Color: Adnexal, Inflammation, Infections, and Pigmentary Disorders ⁸
• Clinical Cases in Skin of Color: Medical, Oncological and Hair Disorders, and Cosmetic Dermatology ⁹
• Dermatology Atlas for Skin of Color ¹⁰
• Fundamentals of Ethnic Hair: The Dermatologist’s Perspective ¹¹
• Light-Based Therapies for Skin of Color ¹²
• Pediatric Skin of Color ¹³
• Skin of Color: A Practical Guide to Dermatologic Diagnosis and Treatment ¹⁴
• Taylor and Kelly’s Dermatology for Skin of Color ¹⁵
• Treatments for Skin of Color ¹⁶

Our program has provided residents with Taylor and Kelly’s Dermatology for Skin of Color¹⁵ and Treatments for Skin of Color.¹⁶ Residents and medical students should search their institution’s electronic library for e-books and other resources including VisualDx, which includes many photographs of SOC that can be used and cited in resident didactics.

There also are a variety of online resources. Mind the Gap is a handbook written by Malone Mukwende, a medical student in London.^17,18 The handbook focuses on common clinical signs and how they present in black and brown skin. Another online resource with clinical images is Skin Deep (https://dftbskindeep.com/), a project aimed at improving the diversity of pediatric skin images. An additional online resource is Brown Skin Matters on Instagram (@brownskinmatters) that shows photographs of dermatologic conditions in SOC; however, these photographs are submitted by users and not independently verified.

I also encourage residents to join the Skin of Color Society, which promotes awareness and excellence within the special interest area of SOC. Some of the society's initiatives include educational series, networking events, diversity town halls, and a scientific symposium. Patient information for common dermatologic diagnoses exists on the society's website (https://skinofcolorsociety.org/). The society waives membership fees for resident applicants who provide a letter of good standing from their residency program. The society hosted the Skin of Color Update virtually this year (September 12–13, 2020). It costs $49 to attend, and the recorded lectures are available to stream through the end of 2020. Our department sponsored residents to attend virtually.

Finally, our department has been taking steps to implement antiracism measures in how we work, learn, conduct research, and treat patients. We are leading a resident book club discussing How to Be an Antiracist¹⁹ by Ibram X. Kendi. Residents are involved in the local chapter of White Coats for Black Lives (https://whitecoats4blacklives.org/). We also have compiled a list of antiracism resources that was shared with the department, including books, documentaries, podcasts, local and online Black-owned businesses to support, and local Black-led nonprofits. 

Final Thoughts

Dermatology residents must be comfortable diagnosing and treating diseases in darker skin tones to provide the best possible care for patients with SOC. Although some common dermatology educational resources have a paucity of clinical images of SOC, there are a variety of additional educational resources through textbooks and websites.

An article recently was published in The New York Times with a headline that read, “Dermatology Has a Problem With Skin Color.” ¹ The article featured interviews with many well-known dermatologists who are experts in skin of color (SOC), and their points followed a similar pattern—skin disease often looks different in patients with darker skin, and diagnoses often are delayed or missed altogether as a consequence of clinical uncertainty. The article included an interview with Jenna Lester, MD, who leads the SOC clinic at the University of California, San Francisco. In the article, she discussed how dermatologists are trained to recognize findings through pattern recognition. However, if we are only trained to diagnose dermatologic diseases on white skin, we will be unable to recognize diseases in patients with darker skin, leading to suboptimal patient care. ¹

Dermatology is a visual specialty, and residents go through thousands of photographs during residency training to distinguish different presentations and unique findings of a variety of skin diseases. Nevertheless, to Dr. Lester’s point, our learning is limited by the photographs and patients that we see.

Additionally, residents training in locations without diverse patient populations rely even more on images in educational resources to recognize clinical presentations in patients with darker skin. A study was published in Cutis earlier this year that surveyed dermatology residents about multiethnic training in residency.² It showed that residents training in less ethnically diverse areas such as the Midwest and Northwest were more likely to agree that dedicated multiethnic clinics and rotations are important to gain competence compared to residents training in more ethnically diverse regions such as the Southeast, Northeast, and Southwest. Most residents believed 1 to 5 hours per month of lectures covering conditions affecting SOC and/or multiethnic skin are needed to become competent.²

Limitations of Educational Resources

The images in dermatology educational resources do not reflect the diversity of our country’s population. A research letter recently was published in the Journal of the American Academy of Dermatology (JAAD) in which the authors assessed the number of images of dark skin—Fitzpatrick skin types V and VI—in dermatology educational resources.³ The authors analyzed images from 8 resources commonly used to study dermatology, including 6 printed texts and 2 online resources. Of the printed texts, Andrews’ Diseases of the Skin had the highest percentage of images of dark skin at 19.9%. Overall, VisualDx had the highest percentage of photographs of dark skin at 28.5%, while DermNet NZ had the lowest of all resources at only 2.8%.³

Similarly, a research letter published in the British Journal of Dermatology reviewed images in 2 standard dermatology textbooks.⁴ Although images of SOC made up 22% to 32% of the overall content, the number of images of sexually transmitted infections in SOC was disproportionate (47%–58%) compared to images of non–sexually transmitted infections (28%). The authors also stated that communities of color often have legacies of mistrust with the health care system, and diagnostic uncertainty can further impair the physician-patient relationship.⁴

The lack of diversity in clinical images and research was further exemplified by recent publications regarding the perniolike eruption associated with coronavirus disease 2019 (COVID-19), commonly referred to as COVID toes. A research letter was published in the British Journal of Dermatology earlier this year about the lack of images of SOC in publications about the cutaneous manifestations of COVID-19.⁵ At that time, there were zero published images of cutaneous COVID-19 manifestations in Fitzpatrick skin types V and VI, yet COVID-19 disproportionately affects Black individuals and other people of color.^5,6 A case series recently was published in JAAD Case Reports that included images of cutaneous COVID-19 findings in patients with Fitzpatrick skin types III through V.⁷ The authors noted that the findings were more subtle on darker skin as the erythema was harder to discern. The inability to identify the perniolike eruption ultimately can delay diagnosis.⁷

Resident Education

Over the past few months, I have reflected on my role as a dermatology resident and my dedication to antiracism in my personal and professional life. It is not a valid response or excuse to say that certain diagnoses are harder to make because of darker skin tone. It is our responsibility to do better for all patients. To that end, our educational resources should reflect our entire patient population.

I have been working with my coresident Annika Weinhammer, MD, on a quality improvement project to strengthen our educational curriculum at the University of Wisconsin regarding SOC. This project aims to enhance our skills as dermatologists in diagnosing and treating diseases in SOC. Moving forward, we have set an expectation that all didactic lectures must include images of SOC. Below, I have listed some of our initiatives along with recommendations for educational resources. There are multiple dermatology textbooks focused on SOC, including the following:

• Clinical Cases in Skin of Color: Adnexal, Inflammation, Infections, and Pigmentary Disorders ⁸
• Clinical Cases in Skin of Color: Medical, Oncological and Hair Disorders, and Cosmetic Dermatology ⁹
• Dermatology Atlas for Skin of Color ¹⁰
• Fundamentals of Ethnic Hair: The Dermatologist’s Perspective ¹¹
• Light-Based Therapies for Skin of Color ¹²
• Pediatric Skin of Color ¹³
• Skin of Color: A Practical Guide to Dermatologic Diagnosis and Treatment ¹⁴
• Taylor and Kelly’s Dermatology for Skin of Color ¹⁵
• Treatments for Skin of Color ¹⁶

Our program has provided residents with Taylor and Kelly’s Dermatology for Skin of Color¹⁵ and Treatments for Skin of Color.¹⁶ Residents and medical students should search their institution’s electronic library for e-books and other resources including VisualDx, which includes many photographs of SOC that can be used and cited in resident didactics.

There also are a variety of online resources. Mind the Gap is a handbook written by Malone Mukwende, a medical student in London.^17,18 The handbook focuses on common clinical signs and how they present in black and brown skin. Another online resource with clinical images is Skin Deep (https://dftbskindeep.com/), a project aimed at improving the diversity of pediatric skin images. An additional online resource is Brown Skin Matters on Instagram (@brownskinmatters) that shows photographs of dermatologic conditions in SOC; however, these photographs are submitted by users and not independently verified.

I also encourage residents to join the Skin of Color Society, which promotes awareness and excellence within the special interest area of SOC. Some of the society's initiatives include educational series, networking events, diversity town halls, and a scientific symposium. Patient information for common dermatologic diagnoses exists on the society's website (https://skinofcolorsociety.org/). The society waives membership fees for resident applicants who provide a letter of good standing from their residency program. The society hosted the Skin of Color Update virtually this year (September 12–13, 2020). It costs $49 to attend, and the recorded lectures are available to stream through the end of 2020. Our department sponsored residents to attend virtually.

Finally, our department has been taking steps to implement antiracism measures in how we work, learn, conduct research, and treat patients. We are leading a resident book club discussing How to Be an Antiracist¹⁹ by Ibram X. Kendi. Residents are involved in the local chapter of White Coats for Black Lives (https://whitecoats4blacklives.org/). We also have compiled a list of antiracism resources that was shared with the department, including books, documentaries, podcasts, local and online Black-owned businesses to support, and local Black-led nonprofits. 

Final Thoughts

Dermatology residents must be comfortable diagnosing and treating diseases in darker skin tones to provide the best possible care for patients with SOC. Although some common dermatology educational resources have a paucity of clinical images of SOC, there are a variety of additional educational resources through textbooks and websites.

An article recently was published in The New York Times with a headline that read, “Dermatology Has a Problem With Skin Color.” ¹ The article featured interviews with many well-known dermatologists who are experts in skin of color (SOC), and their points followed a similar pattern—skin disease often looks different in patients with darker skin, and diagnoses often are delayed or missed altogether as a consequence of clinical uncertainty. The article included an interview with Jenna Lester, MD, who leads the SOC clinic at the University of California, San Francisco. In the article, she discussed how dermatologists are trained to recognize findings through pattern recognition. However, if we are only trained to diagnose dermatologic diseases on white skin, we will be unable to recognize diseases in patients with darker skin, leading to suboptimal patient care. ¹

Dermatology is a visual specialty, and residents go through thousands of photographs during residency training to distinguish different presentations and unique findings of a variety of skin diseases. Nevertheless, to Dr. Lester’s point, our learning is limited by the photographs and patients that we see.

Additionally, residents training in locations without diverse patient populations rely even more on images in educational resources to recognize clinical presentations in patients with darker skin. A study was published in Cutis earlier this year that surveyed dermatology residents about multiethnic training in residency.² It showed that residents training in less ethnically diverse areas such as the Midwest and Northwest were more likely to agree that dedicated multiethnic clinics and rotations are important to gain competence compared to residents training in more ethnically diverse regions such as the Southeast, Northeast, and Southwest. Most residents believed 1 to 5 hours per month of lectures covering conditions affecting SOC and/or multiethnic skin are needed to become competent.²

Limitations of Educational Resources

The images in dermatology educational resources do not reflect the diversity of our country’s population. A research letter recently was published in the Journal of the American Academy of Dermatology (JAAD) in which the authors assessed the number of images of dark skin—Fitzpatrick skin types V and VI—in dermatology educational resources.³ The authors analyzed images from 8 resources commonly used to study dermatology, including 6 printed texts and 2 online resources. Of the printed texts, Andrews’ Diseases of the Skin had the highest percentage of images of dark skin at 19.9%. Overall, VisualDx had the highest percentage of photographs of dark skin at 28.5%, while DermNet NZ had the lowest of all resources at only 2.8%.³

Similarly, a research letter published in the British Journal of Dermatology reviewed images in 2 standard dermatology textbooks.⁴ Although images of SOC made up 22% to 32% of the overall content, the number of images of sexually transmitted infections in SOC was disproportionate (47%–58%) compared to images of non–sexually transmitted infections (28%). The authors also stated that communities of color often have legacies of mistrust with the health care system, and diagnostic uncertainty can further impair the physician-patient relationship.⁴

The lack of diversity in clinical images and research was further exemplified by recent publications regarding the perniolike eruption associated with coronavirus disease 2019 (COVID-19), commonly referred to as COVID toes. A research letter was published in the British Journal of Dermatology earlier this year about the lack of images of SOC in publications about the cutaneous manifestations of COVID-19.⁵ At that time, there were zero published images of cutaneous COVID-19 manifestations in Fitzpatrick skin types V and VI, yet COVID-19 disproportionately affects Black individuals and other people of color.^5,6 A case series recently was published in JAAD Case Reports that included images of cutaneous COVID-19 findings in patients with Fitzpatrick skin types III through V.⁷ The authors noted that the findings were more subtle on darker skin as the erythema was harder to discern. The inability to identify the perniolike eruption ultimately can delay diagnosis.⁷

Resident Education

Over the past few months, I have reflected on my role as a dermatology resident and my dedication to antiracism in my personal and professional life. It is not a valid response or excuse to say that certain diagnoses are harder to make because of darker skin tone. It is our responsibility to do better for all patients. To that end, our educational resources should reflect our entire patient population.

I have been working with my coresident Annika Weinhammer, MD, on a quality improvement project to strengthen our educational curriculum at the University of Wisconsin regarding SOC. This project aims to enhance our skills as dermatologists in diagnosing and treating diseases in SOC. Moving forward, we have set an expectation that all didactic lectures must include images of SOC. Below, I have listed some of our initiatives along with recommendations for educational resources. There are multiple dermatology textbooks focused on SOC, including the following:

• Clinical Cases in Skin of Color: Adnexal, Inflammation, Infections, and Pigmentary Disorders ⁸
• Clinical Cases in Skin of Color: Medical, Oncological and Hair Disorders, and Cosmetic Dermatology ⁹
• Dermatology Atlas for Skin of Color ¹⁰
• Fundamentals of Ethnic Hair: The Dermatologist’s Perspective ¹¹
• Light-Based Therapies for Skin of Color ¹²
• Pediatric Skin of Color ¹³
• Skin of Color: A Practical Guide to Dermatologic Diagnosis and Treatment ¹⁴
• Taylor and Kelly’s Dermatology for Skin of Color ¹⁵
• Treatments for Skin of Color ¹⁶

Our program has provided residents with Taylor and Kelly’s Dermatology for Skin of Color¹⁵ and Treatments for Skin of Color.¹⁶ Residents and medical students should search their institution’s electronic library for e-books and other resources including VisualDx, which includes many photographs of SOC that can be used and cited in resident didactics.

There also are a variety of online resources. Mind the Gap is a handbook written by Malone Mukwende, a medical student in London.^17,18 The handbook focuses on common clinical signs and how they present in black and brown skin. Another online resource with clinical images is Skin Deep (https://dftbskindeep.com/), a project aimed at improving the diversity of pediatric skin images. An additional online resource is Brown Skin Matters on Instagram (@brownskinmatters) that shows photographs of dermatologic conditions in SOC; however, these photographs are submitted by users and not independently verified.

I also encourage residents to join the Skin of Color Society, which promotes awareness and excellence within the special interest area of SOC. Some of the society's initiatives include educational series, networking events, diversity town halls, and a scientific symposium. Patient information for common dermatologic diagnoses exists on the society's website (https://skinofcolorsociety.org/). The society waives membership fees for resident applicants who provide a letter of good standing from their residency program. The society hosted the Skin of Color Update virtually this year (September 12–13, 2020). It costs $49 to attend, and the recorded lectures are available to stream through the end of 2020. Our department sponsored residents to attend virtually.

Finally, our department has been taking steps to implement antiracism measures in how we work, learn, conduct research, and treat patients. We are leading a resident book club discussing How to Be an Antiracist¹⁹ by Ibram X. Kendi. Residents are involved in the local chapter of White Coats for Black Lives (https://whitecoats4blacklives.org/). We also have compiled a list of antiracism resources that was shared with the department, including books, documentaries, podcasts, local and online Black-owned businesses to support, and local Black-led nonprofits. 

Final Thoughts

Dermatology residents must be comfortable diagnosing and treating diseases in darker skin tones to provide the best possible care for patients with SOC. Although some common dermatology educational resources have a paucity of clinical images of SOC, there are a variety of additional educational resources through textbooks and websites.

Abnormal mitochondrial activity in pain-processing areas of the brain may explain why some persons with type 2 diabetes experience painful peripheral neuropathy while others do not, new U.K. study findings have suggested.

A greater ratio of adenosine triphosphate (ATP) – “the cellular energy currency of all life” – to phosphocreatine (PCr) was observed in the somatosensory cortex and right thalamus in those with painful diabetic peripheral neuropathy (DPN). Importantly, this correlated with neuropathic pain symptom intensity as measured by the Neuropathic Pain Symptom Inventory (NPSI) and the Doleur Neuroathique en 4 (DN4).

The findings suggest that altered cerebral phosphorus metabolite ratios may serve as a biomarker of DPN, said the study’s investigators.

“Normally the ATP:Cr ratio will be unaltered, but there’s stress to the brain that might change,” Gordon Sloan, a clinical research fellow within the Diabetes Research Unit at the Royal Hallamshire Hospital in Sheffield (England) said at the virtual annual meeting of the European Association for the Study of Diabetes.

DPN affects around a quarter of patients with type 2 diabetes but treatments are “inadequate”, and “unfortunately fewer than a third of individuals receive 50% or greater pain relief from current neuropathic pain treatments,” Mr. Sloan said. “Ultimately, this lack of understanding of the pathophysiology of the condition is therefore clear rationale to investigate the disease mechanisms further and to find novel targets for treatments,” he added.


 

Brain metabolites offer clues to neuropathic pain levels

The thalamus and primary somatosensory cortex are two key areas of the brain that are involved in the perception of painful stimuli, Mr. Sloan explained. “The thalamus receives most of the slowest sensory impulses from the peripheral nervous system modulating and processing them for relaying the signals to the rest of the pain matrix, including the somatosensory cortex where these sensations are interpreted and localized.”

Prior imaging work by Mr. Sloan’s group and others have shown that there are alterations in the functioning of both these brain areas in those with painful DPN versus healthy volunteers and those with type 2 diabetes but no DPN. So for their current study, Mr. Sloan and associates from Sheffield University and Sheffield Teaching Hospitals National Health Service Trust, used an advanced imaging method – phosphorus magnetic resonance spectroscopy (MRS) – to scan the thalamus and somatosensory cortex of 43 persons with type 2 diabetes and 12 healthy volunteers. Of those with diabetes, 11 had no DPN, 12 had DPN but were not currently in pain, and 20 had painful DPN.

From the scans, three phosphorus metabolite ratios were calculated, which gave an indication of mitochondrial activity: first, the ATP to PCr ratio, which gives a measure of cellular energy status; second, the ATP to inorganic phosphate (Pi) ratio, which measures oxidative phosphorylation; and third, the ratio of phosphomonoesters (PME) to phosphodiesters (PDE), which gives a measure of cell membrane turnover.

“We have measured the ratio of high-energy phosphate levels which are an indirect representation of the balance between energy generation, reserve and usage in the brain,” Mr. Sloan said.

The subjects studied were of a similar age, around 63 years on average, and well matched in terms of their sex and body mass index. Those with diabetes of course had higher blood glucose and glycated hemoglobin than did the healthy volunteers during the scans. Among those with diabetes, those with DPN were significantly more likely to have a longer duration of diabetes (12.5 years for painful DPN and 15.8 years for nonpainful DPN) than were those with no DPN (8.7 years).

Furthermore, those with DPN had higher scores on the Neuropathic Pain Symptom Inventory (NPSI) than did those without, although there was not much difference between those with painful or nonpainful DPN. On the other had, those with painful DPN were more likely to have higher scores when using the Doleur Neuroathique en 4 (DN4) to assess their pain level.

Results showed significant changes in cerebral cellular bioenergetics in the pain processing regions of the brain in those with painful DPN. The ATP:PCr at the thalamus and at the somatosensory cortex was significantly higher in those with painful DPN, compared with healthy volunteers. The other measures of phosphorus metabolite levels (ATP:Pi and PME:PDE) were unaltered.

“We hypothesize that the findings of the study are suggestive of increased energy demands in regions of pain perception due to increased neuronal activity” said Dr. Sloan.

The study’s results add further evidence for cerebral alterations playing a key role in the generation and maintenance of pain in painful DPN.

SOURCE: Sloan S et al. EASD 2020, oral presentation 181.




 

Abnormal mitochondrial activity in pain-processing areas of the brain may explain why some persons with type 2 diabetes experience painful peripheral neuropathy while others do not, new U.K. study findings have suggested.

A greater ratio of adenosine triphosphate (ATP) – “the cellular energy currency of all life” – to phosphocreatine (PCr) was observed in the somatosensory cortex and right thalamus in those with painful diabetic peripheral neuropathy (DPN). Importantly, this correlated with neuropathic pain symptom intensity as measured by the Neuropathic Pain Symptom Inventory (NPSI) and the Doleur Neuroathique en 4 (DN4).

The findings suggest that altered cerebral phosphorus metabolite ratios may serve as a biomarker of DPN, said the study’s investigators.

“Normally the ATP:Cr ratio will be unaltered, but there’s stress to the brain that might change,” Gordon Sloan, a clinical research fellow within the Diabetes Research Unit at the Royal Hallamshire Hospital in Sheffield (England) said at the virtual annual meeting of the European Association for the Study of Diabetes.

DPN affects around a quarter of patients with type 2 diabetes but treatments are “inadequate”, and “unfortunately fewer than a third of individuals receive 50% or greater pain relief from current neuropathic pain treatments,” Mr. Sloan said. “Ultimately, this lack of understanding of the pathophysiology of the condition is therefore clear rationale to investigate the disease mechanisms further and to find novel targets for treatments,” he added.


 

Brain metabolites offer clues to neuropathic pain levels

The thalamus and primary somatosensory cortex are two key areas of the brain that are involved in the perception of painful stimuli, Mr. Sloan explained. “The thalamus receives most of the slowest sensory impulses from the peripheral nervous system modulating and processing them for relaying the signals to the rest of the pain matrix, including the somatosensory cortex where these sensations are interpreted and localized.”

Prior imaging work by Mr. Sloan’s group and others have shown that there are alterations in the functioning of both these brain areas in those with painful DPN versus healthy volunteers and those with type 2 diabetes but no DPN. So for their current study, Mr. Sloan and associates from Sheffield University and Sheffield Teaching Hospitals National Health Service Trust, used an advanced imaging method – phosphorus magnetic resonance spectroscopy (MRS) – to scan the thalamus and somatosensory cortex of 43 persons with type 2 diabetes and 12 healthy volunteers. Of those with diabetes, 11 had no DPN, 12 had DPN but were not currently in pain, and 20 had painful DPN.

From the scans, three phosphorus metabolite ratios were calculated, which gave an indication of mitochondrial activity: first, the ATP to PCr ratio, which gives a measure of cellular energy status; second, the ATP to inorganic phosphate (Pi) ratio, which measures oxidative phosphorylation; and third, the ratio of phosphomonoesters (PME) to phosphodiesters (PDE), which gives a measure of cell membrane turnover.

“We have measured the ratio of high-energy phosphate levels which are an indirect representation of the balance between energy generation, reserve and usage in the brain,” Mr. Sloan said.

The subjects studied were of a similar age, around 63 years on average, and well matched in terms of their sex and body mass index. Those with diabetes of course had higher blood glucose and glycated hemoglobin than did the healthy volunteers during the scans. Among those with diabetes, those with DPN were significantly more likely to have a longer duration of diabetes (12.5 years for painful DPN and 15.8 years for nonpainful DPN) than were those with no DPN (8.7 years).

Furthermore, those with DPN had higher scores on the Neuropathic Pain Symptom Inventory (NPSI) than did those without, although there was not much difference between those with painful or nonpainful DPN. On the other had, those with painful DPN were more likely to have higher scores when using the Doleur Neuroathique en 4 (DN4) to assess their pain level.

Results showed significant changes in cerebral cellular bioenergetics in the pain processing regions of the brain in those with painful DPN. The ATP:PCr at the thalamus and at the somatosensory cortex was significantly higher in those with painful DPN, compared with healthy volunteers. The other measures of phosphorus metabolite levels (ATP:Pi and PME:PDE) were unaltered.

“We hypothesize that the findings of the study are suggestive of increased energy demands in regions of pain perception due to increased neuronal activity” said Dr. Sloan.

The study’s results add further evidence for cerebral alterations playing a key role in the generation and maintenance of pain in painful DPN.

SOURCE: Sloan S et al. EASD 2020, oral presentation 181.




 

Abnormal mitochondrial activity in pain-processing areas of the brain may explain why some persons with type 2 diabetes experience painful peripheral neuropathy while others do not, new U.K. study findings have suggested.

A greater ratio of adenosine triphosphate (ATP) – “the cellular energy currency of all life” – to phosphocreatine (PCr) was observed in the somatosensory cortex and right thalamus in those with painful diabetic peripheral neuropathy (DPN). Importantly, this correlated with neuropathic pain symptom intensity as measured by the Neuropathic Pain Symptom Inventory (NPSI) and the Doleur Neuroathique en 4 (DN4).

The findings suggest that altered cerebral phosphorus metabolite ratios may serve as a biomarker of DPN, said the study’s investigators.

“Normally the ATP:Cr ratio will be unaltered, but there’s stress to the brain that might change,” Gordon Sloan, a clinical research fellow within the Diabetes Research Unit at the Royal Hallamshire Hospital in Sheffield (England) said at the virtual annual meeting of the European Association for the Study of Diabetes.

DPN affects around a quarter of patients with type 2 diabetes but treatments are “inadequate”, and “unfortunately fewer than a third of individuals receive 50% or greater pain relief from current neuropathic pain treatments,” Mr. Sloan said. “Ultimately, this lack of understanding of the pathophysiology of the condition is therefore clear rationale to investigate the disease mechanisms further and to find novel targets for treatments,” he added.


 

Brain metabolites offer clues to neuropathic pain levels

The thalamus and primary somatosensory cortex are two key areas of the brain that are involved in the perception of painful stimuli, Mr. Sloan explained. “The thalamus receives most of the slowest sensory impulses from the peripheral nervous system modulating and processing them for relaying the signals to the rest of the pain matrix, including the somatosensory cortex where these sensations are interpreted and localized.”

Prior imaging work by Mr. Sloan’s group and others have shown that there are alterations in the functioning of both these brain areas in those with painful DPN versus healthy volunteers and those with type 2 diabetes but no DPN. So for their current study, Mr. Sloan and associates from Sheffield University and Sheffield Teaching Hospitals National Health Service Trust, used an advanced imaging method – phosphorus magnetic resonance spectroscopy (MRS) – to scan the thalamus and somatosensory cortex of 43 persons with type 2 diabetes and 12 healthy volunteers. Of those with diabetes, 11 had no DPN, 12 had DPN but were not currently in pain, and 20 had painful DPN.

From the scans, three phosphorus metabolite ratios were calculated, which gave an indication of mitochondrial activity: first, the ATP to PCr ratio, which gives a measure of cellular energy status; second, the ATP to inorganic phosphate (Pi) ratio, which measures oxidative phosphorylation; and third, the ratio of phosphomonoesters (PME) to phosphodiesters (PDE), which gives a measure of cell membrane turnover.

“We have measured the ratio of high-energy phosphate levels which are an indirect representation of the balance between energy generation, reserve and usage in the brain,” Mr. Sloan said.

The subjects studied were of a similar age, around 63 years on average, and well matched in terms of their sex and body mass index. Those with diabetes of course had higher blood glucose and glycated hemoglobin than did the healthy volunteers during the scans. Among those with diabetes, those with DPN were significantly more likely to have a longer duration of diabetes (12.5 years for painful DPN and 15.8 years for nonpainful DPN) than were those with no DPN (8.7 years).

Furthermore, those with DPN had higher scores on the Neuropathic Pain Symptom Inventory (NPSI) than did those without, although there was not much difference between those with painful or nonpainful DPN. On the other had, those with painful DPN were more likely to have higher scores when using the Doleur Neuroathique en 4 (DN4) to assess their pain level.

Results showed significant changes in cerebral cellular bioenergetics in the pain processing regions of the brain in those with painful DPN. The ATP:PCr at the thalamus and at the somatosensory cortex was significantly higher in those with painful DPN, compared with healthy volunteers. The other measures of phosphorus metabolite levels (ATP:Pi and PME:PDE) were unaltered.

“We hypothesize that the findings of the study are suggestive of increased energy demands in regions of pain perception due to increased neuronal activity” said Dr. Sloan.

The study’s results add further evidence for cerebral alterations playing a key role in the generation and maintenance of pain in painful DPN.

SOURCE: Sloan S et al. EASD 2020, oral presentation 181.




 

A pathologic complete response (pCR) to targeted therapy in HER2-positive breast cancer portends good long-term outcomes, according to final results of the phase 3 NeoALTTO/BIG 1-06 trial. In fact, for the majority of women, pCR appears to be a marker of cure.

Courtesy of VHIO

The trial was conducted among 455 women with HER2-positive breast cancer tumors measuring at least 2 cm who were randomized to neoadjuvant trastuzumab, lapatinib, or both drugs in combination, each together with paclitaxel, followed by more chemotherapy and more of the same targeted therapy after surgery.

Relative to trastuzumab alone, trastuzumab plus lapatinib improved rates of pCR, as shown by data published in The Lancet in 2012. However, the dual therapy did not significantly prolong event-free or overall survival, according to data published in The Lancet Oncology in 2014. Findings were similar in an update at a median follow-up of 6.7 years, published in the European Journal of Cancer in 2019.

Study investigator Paolo Nuciforo, MD, PhD, of the Vall d’Hebron Institute of Oncology in Barcelona, reported the trial’s final results, now at a median follow-up of 9.7 years, at the 12th European Breast Cancer Conference.

There were no significant differences in 9-year outcomes by specific HER2-targeted therapy. However, in a landmark analysis among women who were event free and still on follow-up 30 weeks after randomization, those achieving pCR with any of the therapies were 52% less likely to experience events and 63% less likely to die. Benefit was greatest in the subset of patients with hormone receptor–negative disease.

“The long-term follow-up confirms that, independent of the treatment regimen that we use – in this case, the dual blockade was with lapatinib, but similar results can be expected with other dual blockade – the pCR is a very robust surrogate biomarker of long-term survival,” Dr. Nuciforo commented in a press conference, noting that dual trastuzumab and pertuzumab has emerged as the standard of care.

“If we really pay attention to the curve, it’s maybe interesting to see that, after year 6, we actually don’t see any events in the pCR population. So this means that these patients are almost cured. We cannot say the word ‘cure’ in cancer, but it’s very reassuring to see the long-term survival analysis support the use of pCR as an endpoint,” he elaborated.

“Our results support the design of future trial concepts in HER2-positive early breast cancer which use pCR as an early efficacy readout of long-term benefit to escalate or deescalate therapy, particularly for hormone receptor–negative tumors,” Dr. Nuciforo concluded.
 

Support for current practice

“The study lends support for the current practice of risk-stratifying by pCR as well as making treatment decisions regarding T-DM1 [trastuzumab emtansine], and there hasn’t been a big change between 5-year and 9-year outcomes,” Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, commented in an interview.

The lack of late events in the group with pCR technically meets the definition of cure, Dr. Carey said. “I think it speaks to the relatively early relapse risk in HER2-positive breast cancer and the impact of anti-HER2 therapy that carries forward. In general, these are findings similar to long-term findings of other trials and I suspect will be the same for any regimen.”

Although the analysis of dual lapatinib-trastuzumab therapy was underpowered, the trends seen align with favorable results in the adjuvant APHINITY trial (which combined trastuzumab with pertuzumab) and the neoadjuvant CALGB 40601 trial (which combined trastuzumab with lapatinib), according to Dr. Carey. “There has been a trend in every other study [of dual therapy] performed, so this is consistent.”
 

Study details

NeoALTTO is noteworthy for having the longest follow-up among all neoadjuvant studies of dual HER2 blockade in early breast cancer, Dr. Nuciforo said.

He reported no significant difference in survival between the treatment arms at 9 years.

The 9-year rate of event-free survival was 69% with lapatinib-trastuzumab, 63% with lapatinib alone, and 65% with trastuzumab alone. The corresponding 9-year rates of overall survival were 80%, 77%, and 76%, respectively.

However, there were significant differences in event-free and overall survival among women who achieved pCR and those who did not.

“pCR was achieved for almost twice as many patients treated with dual HER2 blockade, compared with patients in the single-agent arms,” Dr. Nuciforo pointed out. The pCR rate was 51.3% with lapatinib-trastuzumab, 24.7% with lapatinib alone, and 29.5% with trastuzumab alone.

Relative to peers who did not achieve pCR, women who did had better 9-year event-free survival (77% vs. 61%; adjusted hazard ratio, 0.48; P = .0008). The benefit was stronger in hormone receptor–negative disease (HR, 0.43; P = .002) than in hormone receptor–positive disease (HR, 0.60; P = .15).

The pattern was similar for overall survival at 9 years – 88% in those who achieved a pCR and 72% in those who did not (adjusted HR, 0.37; P = .0004). Again, greater benefit was seen in hormone receptor–negative disease (HR, 0.33; P = .002) than in hormone receptor–positive disease (HR, 0.44; P = .09).

“Biomarker-driven approaches may improve selection of those patients who are more likely to respond to anti-HER2 therapies,” Dr. Nuciforo proposed.

From 6 years onward, there were no additional fatal adverse events or nonfatal serious adverse events recorded, and no additional primary cardiac endpoints were recorded.

The study was funded by Novartis. Dr. Nuciforo and Dr. Carey disclosed no conflicts of interest.

SOURCE: Nuciforo P et al. EBCC-12 Virtual Conference, Abstract 23.

A pathologic complete response (pCR) to targeted therapy in HER2-positive breast cancer portends good long-term outcomes, according to final results of the phase 3 NeoALTTO/BIG 1-06 trial. In fact, for the majority of women, pCR appears to be a marker of cure.

Courtesy of VHIO

The trial was conducted among 455 women with HER2-positive breast cancer tumors measuring at least 2 cm who were randomized to neoadjuvant trastuzumab, lapatinib, or both drugs in combination, each together with paclitaxel, followed by more chemotherapy and more of the same targeted therapy after surgery.

Relative to trastuzumab alone, trastuzumab plus lapatinib improved rates of pCR, as shown by data published in The Lancet in 2012. However, the dual therapy did not significantly prolong event-free or overall survival, according to data published in The Lancet Oncology in 2014. Findings were similar in an update at a median follow-up of 6.7 years, published in the European Journal of Cancer in 2019.

Study investigator Paolo Nuciforo, MD, PhD, of the Vall d’Hebron Institute of Oncology in Barcelona, reported the trial’s final results, now at a median follow-up of 9.7 years, at the 12th European Breast Cancer Conference.

There were no significant differences in 9-year outcomes by specific HER2-targeted therapy. However, in a landmark analysis among women who were event free and still on follow-up 30 weeks after randomization, those achieving pCR with any of the therapies were 52% less likely to experience events and 63% less likely to die. Benefit was greatest in the subset of patients with hormone receptor–negative disease.

“The long-term follow-up confirms that, independent of the treatment regimen that we use – in this case, the dual blockade was with lapatinib, but similar results can be expected with other dual blockade – the pCR is a very robust surrogate biomarker of long-term survival,” Dr. Nuciforo commented in a press conference, noting that dual trastuzumab and pertuzumab has emerged as the standard of care.

“If we really pay attention to the curve, it’s maybe interesting to see that, after year 6, we actually don’t see any events in the pCR population. So this means that these patients are almost cured. We cannot say the word ‘cure’ in cancer, but it’s very reassuring to see the long-term survival analysis support the use of pCR as an endpoint,” he elaborated.

“Our results support the design of future trial concepts in HER2-positive early breast cancer which use pCR as an early efficacy readout of long-term benefit to escalate or deescalate therapy, particularly for hormone receptor–negative tumors,” Dr. Nuciforo concluded.
 

Support for current practice

“The study lends support for the current practice of risk-stratifying by pCR as well as making treatment decisions regarding T-DM1 [trastuzumab emtansine], and there hasn’t been a big change between 5-year and 9-year outcomes,” Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, commented in an interview.

The lack of late events in the group with pCR technically meets the definition of cure, Dr. Carey said. “I think it speaks to the relatively early relapse risk in HER2-positive breast cancer and the impact of anti-HER2 therapy that carries forward. In general, these are findings similar to long-term findings of other trials and I suspect will be the same for any regimen.”

Although the analysis of dual lapatinib-trastuzumab therapy was underpowered, the trends seen align with favorable results in the adjuvant APHINITY trial (which combined trastuzumab with pertuzumab) and the neoadjuvant CALGB 40601 trial (which combined trastuzumab with lapatinib), according to Dr. Carey. “There has been a trend in every other study [of dual therapy] performed, so this is consistent.”
 

Study details

NeoALTTO is noteworthy for having the longest follow-up among all neoadjuvant studies of dual HER2 blockade in early breast cancer, Dr. Nuciforo said.

He reported no significant difference in survival between the treatment arms at 9 years.

The 9-year rate of event-free survival was 69% with lapatinib-trastuzumab, 63% with lapatinib alone, and 65% with trastuzumab alone. The corresponding 9-year rates of overall survival were 80%, 77%, and 76%, respectively.

However, there were significant differences in event-free and overall survival among women who achieved pCR and those who did not.

“pCR was achieved for almost twice as many patients treated with dual HER2 blockade, compared with patients in the single-agent arms,” Dr. Nuciforo pointed out. The pCR rate was 51.3% with lapatinib-trastuzumab, 24.7% with lapatinib alone, and 29.5% with trastuzumab alone.

Relative to peers who did not achieve pCR, women who did had better 9-year event-free survival (77% vs. 61%; adjusted hazard ratio, 0.48; P = .0008). The benefit was stronger in hormone receptor–negative disease (HR, 0.43; P = .002) than in hormone receptor–positive disease (HR, 0.60; P = .15).

The pattern was similar for overall survival at 9 years – 88% in those who achieved a pCR and 72% in those who did not (adjusted HR, 0.37; P = .0004). Again, greater benefit was seen in hormone receptor–negative disease (HR, 0.33; P = .002) than in hormone receptor–positive disease (HR, 0.44; P = .09).

“Biomarker-driven approaches may improve selection of those patients who are more likely to respond to anti-HER2 therapies,” Dr. Nuciforo proposed.

From 6 years onward, there were no additional fatal adverse events or nonfatal serious adverse events recorded, and no additional primary cardiac endpoints were recorded.

The study was funded by Novartis. Dr. Nuciforo and Dr. Carey disclosed no conflicts of interest.

SOURCE: Nuciforo P et al. EBCC-12 Virtual Conference, Abstract 23.

A pathologic complete response (pCR) to targeted therapy in HER2-positive breast cancer portends good long-term outcomes, according to final results of the phase 3 NeoALTTO/BIG 1-06 trial. In fact, for the majority of women, pCR appears to be a marker of cure.

Courtesy of VHIO

The trial was conducted among 455 women with HER2-positive breast cancer tumors measuring at least 2 cm who were randomized to neoadjuvant trastuzumab, lapatinib, or both drugs in combination, each together with paclitaxel, followed by more chemotherapy and more of the same targeted therapy after surgery.

Relative to trastuzumab alone, trastuzumab plus lapatinib improved rates of pCR, as shown by data published in The Lancet in 2012. However, the dual therapy did not significantly prolong event-free or overall survival, according to data published in The Lancet Oncology in 2014. Findings were similar in an update at a median follow-up of 6.7 years, published in the European Journal of Cancer in 2019.

Study investigator Paolo Nuciforo, MD, PhD, of the Vall d’Hebron Institute of Oncology in Barcelona, reported the trial’s final results, now at a median follow-up of 9.7 years, at the 12th European Breast Cancer Conference.

There were no significant differences in 9-year outcomes by specific HER2-targeted therapy. However, in a landmark analysis among women who were event free and still on follow-up 30 weeks after randomization, those achieving pCR with any of the therapies were 52% less likely to experience events and 63% less likely to die. Benefit was greatest in the subset of patients with hormone receptor–negative disease.

“The long-term follow-up confirms that, independent of the treatment regimen that we use – in this case, the dual blockade was with lapatinib, but similar results can be expected with other dual blockade – the pCR is a very robust surrogate biomarker of long-term survival,” Dr. Nuciforo commented in a press conference, noting that dual trastuzumab and pertuzumab has emerged as the standard of care.

“If we really pay attention to the curve, it’s maybe interesting to see that, after year 6, we actually don’t see any events in the pCR population. So this means that these patients are almost cured. We cannot say the word ‘cure’ in cancer, but it’s very reassuring to see the long-term survival analysis support the use of pCR as an endpoint,” he elaborated.

“Our results support the design of future trial concepts in HER2-positive early breast cancer which use pCR as an early efficacy readout of long-term benefit to escalate or deescalate therapy, particularly for hormone receptor–negative tumors,” Dr. Nuciforo concluded.
 

Support for current practice

“The study lends support for the current practice of risk-stratifying by pCR as well as making treatment decisions regarding T-DM1 [trastuzumab emtansine], and there hasn’t been a big change between 5-year and 9-year outcomes,” Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, commented in an interview.

The lack of late events in the group with pCR technically meets the definition of cure, Dr. Carey said. “I think it speaks to the relatively early relapse risk in HER2-positive breast cancer and the impact of anti-HER2 therapy that carries forward. In general, these are findings similar to long-term findings of other trials and I suspect will be the same for any regimen.”

Although the analysis of dual lapatinib-trastuzumab therapy was underpowered, the trends seen align with favorable results in the adjuvant APHINITY trial (which combined trastuzumab with pertuzumab) and the neoadjuvant CALGB 40601 trial (which combined trastuzumab with lapatinib), according to Dr. Carey. “There has been a trend in every other study [of dual therapy] performed, so this is consistent.”
 

Study details

NeoALTTO is noteworthy for having the longest follow-up among all neoadjuvant studies of dual HER2 blockade in early breast cancer, Dr. Nuciforo said.

He reported no significant difference in survival between the treatment arms at 9 years.

The 9-year rate of event-free survival was 69% with lapatinib-trastuzumab, 63% with lapatinib alone, and 65% with trastuzumab alone. The corresponding 9-year rates of overall survival were 80%, 77%, and 76%, respectively.

However, there were significant differences in event-free and overall survival among women who achieved pCR and those who did not.

“pCR was achieved for almost twice as many patients treated with dual HER2 blockade, compared with patients in the single-agent arms,” Dr. Nuciforo pointed out. The pCR rate was 51.3% with lapatinib-trastuzumab, 24.7% with lapatinib alone, and 29.5% with trastuzumab alone.

Relative to peers who did not achieve pCR, women who did had better 9-year event-free survival (77% vs. 61%; adjusted hazard ratio, 0.48; P = .0008). The benefit was stronger in hormone receptor–negative disease (HR, 0.43; P = .002) than in hormone receptor–positive disease (HR, 0.60; P = .15).

The pattern was similar for overall survival at 9 years – 88% in those who achieved a pCR and 72% in those who did not (adjusted HR, 0.37; P = .0004). Again, greater benefit was seen in hormone receptor–negative disease (HR, 0.33; P = .002) than in hormone receptor–positive disease (HR, 0.44; P = .09).

“Biomarker-driven approaches may improve selection of those patients who are more likely to respond to anti-HER2 therapies,” Dr. Nuciforo proposed.

From 6 years onward, there were no additional fatal adverse events or nonfatal serious adverse events recorded, and no additional primary cardiac endpoints were recorded.

The study was funded by Novartis. Dr. Nuciforo and Dr. Carey disclosed no conflicts of interest.

SOURCE: Nuciforo P et al. EBCC-12 Virtual Conference, Abstract 23.

ANSWER

The correct answer is koebnerization of pre-existing psoriasis (choice “c”).

DISCUSSION

Tattoos have been known to cause bacterial infection (choice “a”), but this was unlikely given the diffuse nature of the rash and the lack of pain or adenopathy. Allergic reactions to tattoo dyes (choice “b”) are certainly common, but usually red or yellow dyes—which were not used for this tattoo—provoke the worst reactions. Furthermore, itching would have been a more prominent feature of the patient's complaint. Had it been fungal infection (choice “d”), the steroid cream would have made it worse.

One possibility remained: the so-called isomorphic phenomenon (otherwise known as koebnerization). First described by Heinrich Koebner in the mid-19th century, koebnerization is characterized by the appearance of psoriasis in traumatized skin such as surgical wounds, abrasions, burns, or even tattoos. Several other conditions also exhibit this same linear response to trauma, including warts, molluscum, and lichen planus.

To test for this diagnosis, corroborative findings of psoriasis were sought and found in the patient’s nails. His history of rashes on the knees and elbows also contributed to establishing the diagnosis. Moreover, his complaint of arthritis was quite suggestive of psoriatic arthropathy, which afflicts about 25% of patients with psoriasis and has little to do with the severity of the skin disease itself. Once the diagnosis became more apparent, the patient recalled a family history of psoriasis. Had any question remained, a biopsy could remove doubt.

TREATMENT

For the patient, twice-daily application of a stronger steroid cream (augmented betamethasone) was prescribed. Though this quickly cleared the koebnerizing psoriasis, it is likely we haven’t seen the last of this disease.

ANSWER

The correct answer is koebnerization of pre-existing psoriasis (choice “c”).

DISCUSSION

Tattoos have been known to cause bacterial infection (choice “a”), but this was unlikely given the diffuse nature of the rash and the lack of pain or adenopathy. Allergic reactions to tattoo dyes (choice “b”) are certainly common, but usually red or yellow dyes—which were not used for this tattoo—provoke the worst reactions. Furthermore, itching would have been a more prominent feature of the patient's complaint. Had it been fungal infection (choice “d”), the steroid cream would have made it worse.

One possibility remained: the so-called isomorphic phenomenon (otherwise known as koebnerization). First described by Heinrich Koebner in the mid-19th century, koebnerization is characterized by the appearance of psoriasis in traumatized skin such as surgical wounds, abrasions, burns, or even tattoos. Several other conditions also exhibit this same linear response to trauma, including warts, molluscum, and lichen planus.

To test for this diagnosis, corroborative findings of psoriasis were sought and found in the patient’s nails. His history of rashes on the knees and elbows also contributed to establishing the diagnosis. Moreover, his complaint of arthritis was quite suggestive of psoriatic arthropathy, which afflicts about 25% of patients with psoriasis and has little to do with the severity of the skin disease itself. Once the diagnosis became more apparent, the patient recalled a family history of psoriasis. Had any question remained, a biopsy could remove doubt.

TREATMENT

For the patient, twice-daily application of a stronger steroid cream (augmented betamethasone) was prescribed. Though this quickly cleared the koebnerizing psoriasis, it is likely we haven’t seen the last of this disease.

ANSWER

The correct answer is koebnerization of pre-existing psoriasis (choice “c”).

DISCUSSION

Tattoos have been known to cause bacterial infection (choice “a”), but this was unlikely given the diffuse nature of the rash and the lack of pain or adenopathy. Allergic reactions to tattoo dyes (choice “b”) are certainly common, but usually red or yellow dyes—which were not used for this tattoo—provoke the worst reactions. Furthermore, itching would have been a more prominent feature of the patient's complaint. Had it been fungal infection (choice “d”), the steroid cream would have made it worse.

One possibility remained: the so-called isomorphic phenomenon (otherwise known as koebnerization). First described by Heinrich Koebner in the mid-19th century, koebnerization is characterized by the appearance of psoriasis in traumatized skin such as surgical wounds, abrasions, burns, or even tattoos. Several other conditions also exhibit this same linear response to trauma, including warts, molluscum, and lichen planus.

To test for this diagnosis, corroborative findings of psoriasis were sought and found in the patient’s nails. His history of rashes on the knees and elbows also contributed to establishing the diagnosis. Moreover, his complaint of arthritis was quite suggestive of psoriatic arthropathy, which afflicts about 25% of patients with psoriasis and has little to do with the severity of the skin disease itself. Once the diagnosis became more apparent, the patient recalled a family history of psoriasis. Had any question remained, a biopsy could remove doubt.

TREATMENT

For the patient, twice-daily application of a stronger steroid cream (augmented betamethasone) was prescribed. Though this quickly cleared the koebnerizing psoriasis, it is likely we haven’t seen the last of this disease.

The combined features of benign breast disease may help better personalize breast cancer screening strategies, according to a retrospective cohort study reported at the 12th European Breast Cancer Conference.

“Benign breast disease is a key risk factor for breast cancer risk prediction,” commented presenting investigator Marta Román, PhD, of the Hospital del Mar Medical Research Institute in Barcelona. “Those women who have had a benign breast disease diagnosis have an increased risk that lasts for at least 20 years.”

To assess the combined influence of various attributes of benign breast disease, the investigators studied 629,087 women, aged 50-69 years, in Spain who underwent population-based mammographic breast cancer screening during 1994-2015 and did not have breast cancer at their prevalent (first) screen. The mean follow-up was 7.8 years.

Results showed that breast cancer risk was about three times higher for women with benign breast disease that was proliferative or that was detected on an incident screen, relative to peers with no benign breast disease. When combinations of factors were considered, breast cancer risk was most elevated – more than four times higher – for women with proliferative benign breast disease with atypia detected on an incident screen.

“We believe that these findings should be considered when discussing risk-based personalized screening strategies because these differences between prevalent and incident screens might be important if we want to personalize the screening, whether it’s the first time a woman comes to the screening program or a subsequent screen,” Dr. Román said.
 

Practice changing?

The study’s large size and population-based design, likely permitting capture of most biopsy results, are strengths, Mark David Pearlman, MD, of the University of Michigan, Ann Arbor, commented in an interview.

But its observational, retrospective nature opens the study up to biases, such as uncertainty as to how many women were symptomatic at the time of their mammogram and the likelihood of heightened monitoring after a biopsy showing hyperplasia, Dr. Pearlman cautioned.

“Moreover, the relative risk in this study for proliferative benign breast disease without atypia is substantially higher than prior observations of this group. This discrepancy was not discussed by the authors,” Dr. Pearlman said.

At present, women’s risk of breast cancer is predicted using well-validated models that include the question of prior breast biopsies, such as the Gail Model, the Tyrer-Cuzick model (IBIS tool), and the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, Dr. Pearlman noted.

“This study, without further validation within a model, would not change risk assessment,” he said, disagreeing with the investigators’ conclusions. “What I would say is that further study to determine how to use this observation to decide if any change in screening or management should occur would be more appropriate.”
 

Study details

The 629,087 women studied underwent 2,327,384 screens, Dr. Román reported. In total, screening detected 9,184 cases of benign breast disease and 9,431 breast cancers.

Breast cancer was diagnosed in 2.4% and 3.0% of women with benign breast disease detected on prevalent and incident screens, respectively, compared with 1.5% of women without any benign breast disease detected.

Elevation of breast cancer risk varied across benign breast disease subtype. Relative to peers without any benign disease, risk was significantly elevated for women with nonproliferative disease (adjusted hazard ratio, 1.95), proliferative disease without atypia (aHR, 3.19), and proliferative disease with atypia (aHR, 3.82).

Similarly, elevation of risk varied depending on the screening at which the benign disease was detected. Risk was significantly elevated when the disease was found at prevalent screens (aHR, 1.87) and more so when it was found at incident screens (aHR, 2.67).

There was no significant interaction of these two factors (P = .83). However, when combinations were considered, risk was highest for women with proliferative benign breast disease with atypia detected on incident screens (aHR, 4.35) or prevalent screens (aHR, 3.35), and women with proliferative benign breast disease without atypia detected on incident screens (aHR, 3.83).

This study was supported by grants from Instituto de Salud Carlos III FEDER and by the Research Network on Health Services in Chronic Diseases. Dr. Román and Dr. Pearlman disclosed no conflicts of interest.

SOURCE: Román M et al. EBCC-12 Virtual Conference, Abstract 15.

The combined features of benign breast disease may help better personalize breast cancer screening strategies, according to a retrospective cohort study reported at the 12th European Breast Cancer Conference.

“Benign breast disease is a key risk factor for breast cancer risk prediction,” commented presenting investigator Marta Román, PhD, of the Hospital del Mar Medical Research Institute in Barcelona. “Those women who have had a benign breast disease diagnosis have an increased risk that lasts for at least 20 years.”

To assess the combined influence of various attributes of benign breast disease, the investigators studied 629,087 women, aged 50-69 years, in Spain who underwent population-based mammographic breast cancer screening during 1994-2015 and did not have breast cancer at their prevalent (first) screen. The mean follow-up was 7.8 years.

Results showed that breast cancer risk was about three times higher for women with benign breast disease that was proliferative or that was detected on an incident screen, relative to peers with no benign breast disease. When combinations of factors were considered, breast cancer risk was most elevated – more than four times higher – for women with proliferative benign breast disease with atypia detected on an incident screen.

“We believe that these findings should be considered when discussing risk-based personalized screening strategies because these differences between prevalent and incident screens might be important if we want to personalize the screening, whether it’s the first time a woman comes to the screening program or a subsequent screen,” Dr. Román said.
 

Practice changing?

The study’s large size and population-based design, likely permitting capture of most biopsy results, are strengths, Mark David Pearlman, MD, of the University of Michigan, Ann Arbor, commented in an interview.

But its observational, retrospective nature opens the study up to biases, such as uncertainty as to how many women were symptomatic at the time of their mammogram and the likelihood of heightened monitoring after a biopsy showing hyperplasia, Dr. Pearlman cautioned.

“Moreover, the relative risk in this study for proliferative benign breast disease without atypia is substantially higher than prior observations of this group. This discrepancy was not discussed by the authors,” Dr. Pearlman said.

At present, women’s risk of breast cancer is predicted using well-validated models that include the question of prior breast biopsies, such as the Gail Model, the Tyrer-Cuzick model (IBIS tool), and the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, Dr. Pearlman noted.

“This study, without further validation within a model, would not change risk assessment,” he said, disagreeing with the investigators’ conclusions. “What I would say is that further study to determine how to use this observation to decide if any change in screening or management should occur would be more appropriate.”
 

Study details

The 629,087 women studied underwent 2,327,384 screens, Dr. Román reported. In total, screening detected 9,184 cases of benign breast disease and 9,431 breast cancers.

Breast cancer was diagnosed in 2.4% and 3.0% of women with benign breast disease detected on prevalent and incident screens, respectively, compared with 1.5% of women without any benign breast disease detected.

Elevation of breast cancer risk varied across benign breast disease subtype. Relative to peers without any benign disease, risk was significantly elevated for women with nonproliferative disease (adjusted hazard ratio, 1.95), proliferative disease without atypia (aHR, 3.19), and proliferative disease with atypia (aHR, 3.82).

Similarly, elevation of risk varied depending on the screening at which the benign disease was detected. Risk was significantly elevated when the disease was found at prevalent screens (aHR, 1.87) and more so when it was found at incident screens (aHR, 2.67).

There was no significant interaction of these two factors (P = .83). However, when combinations were considered, risk was highest for women with proliferative benign breast disease with atypia detected on incident screens (aHR, 4.35) or prevalent screens (aHR, 3.35), and women with proliferative benign breast disease without atypia detected on incident screens (aHR, 3.83).

This study was supported by grants from Instituto de Salud Carlos III FEDER and by the Research Network on Health Services in Chronic Diseases. Dr. Román and Dr. Pearlman disclosed no conflicts of interest.

SOURCE: Román M et al. EBCC-12 Virtual Conference, Abstract 15.

The combined features of benign breast disease may help better personalize breast cancer screening strategies, according to a retrospective cohort study reported at the 12th European Breast Cancer Conference.

“Benign breast disease is a key risk factor for breast cancer risk prediction,” commented presenting investigator Marta Román, PhD, of the Hospital del Mar Medical Research Institute in Barcelona. “Those women who have had a benign breast disease diagnosis have an increased risk that lasts for at least 20 years.”

To assess the combined influence of various attributes of benign breast disease, the investigators studied 629,087 women, aged 50-69 years, in Spain who underwent population-based mammographic breast cancer screening during 1994-2015 and did not have breast cancer at their prevalent (first) screen. The mean follow-up was 7.8 years.

Results showed that breast cancer risk was about three times higher for women with benign breast disease that was proliferative or that was detected on an incident screen, relative to peers with no benign breast disease. When combinations of factors were considered, breast cancer risk was most elevated – more than four times higher – for women with proliferative benign breast disease with atypia detected on an incident screen.

“We believe that these findings should be considered when discussing risk-based personalized screening strategies because these differences between prevalent and incident screens might be important if we want to personalize the screening, whether it’s the first time a woman comes to the screening program or a subsequent screen,” Dr. Román said.
 

Practice changing?

The study’s large size and population-based design, likely permitting capture of most biopsy results, are strengths, Mark David Pearlman, MD, of the University of Michigan, Ann Arbor, commented in an interview.

But its observational, retrospective nature opens the study up to biases, such as uncertainty as to how many women were symptomatic at the time of their mammogram and the likelihood of heightened monitoring after a biopsy showing hyperplasia, Dr. Pearlman cautioned.

“Moreover, the relative risk in this study for proliferative benign breast disease without atypia is substantially higher than prior observations of this group. This discrepancy was not discussed by the authors,” Dr. Pearlman said.

At present, women’s risk of breast cancer is predicted using well-validated models that include the question of prior breast biopsies, such as the Gail Model, the Tyrer-Cuzick model (IBIS tool), and the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, Dr. Pearlman noted.

“This study, without further validation within a model, would not change risk assessment,” he said, disagreeing with the investigators’ conclusions. “What I would say is that further study to determine how to use this observation to decide if any change in screening or management should occur would be more appropriate.”
 

Study details

The 629,087 women studied underwent 2,327,384 screens, Dr. Román reported. In total, screening detected 9,184 cases of benign breast disease and 9,431 breast cancers.

Breast cancer was diagnosed in 2.4% and 3.0% of women with benign breast disease detected on prevalent and incident screens, respectively, compared with 1.5% of women without any benign breast disease detected.

Elevation of breast cancer risk varied across benign breast disease subtype. Relative to peers without any benign disease, risk was significantly elevated for women with nonproliferative disease (adjusted hazard ratio, 1.95), proliferative disease without atypia (aHR, 3.19), and proliferative disease with atypia (aHR, 3.82).

Similarly, elevation of risk varied depending on the screening at which the benign disease was detected. Risk was significantly elevated when the disease was found at prevalent screens (aHR, 1.87) and more so when it was found at incident screens (aHR, 2.67).

There was no significant interaction of these two factors (P = .83). However, when combinations were considered, risk was highest for women with proliferative benign breast disease with atypia detected on incident screens (aHR, 4.35) or prevalent screens (aHR, 3.35), and women with proliferative benign breast disease without atypia detected on incident screens (aHR, 3.83).

This study was supported by grants from Instituto de Salud Carlos III FEDER and by the Research Network on Health Services in Chronic Diseases. Dr. Román and Dr. Pearlman disclosed no conflicts of interest.

SOURCE: Román M et al. EBCC-12 Virtual Conference, Abstract 15.

A COVID-19 vaccine could be proven effective within the last months of 2020, with distribution of first doses possible before the end of the year, according to Anthony S. Fauci, MD, director, National Institute of Allergy and Infectious Diseases, Bethesda, Md.

“Given the rate of infection that’s going on in this country, and the distribution of the clinical trial sites involving tens of thousands of volunteers, we project that we will have an answer as to whether or not we have a safe and effective vaccine by November or December,” Dr. Fauci said today in his virtual keynote address during the annual meeting of the American College of Chest Physicians.

“It may come earlier -- this month, in October,” he added in his remarks. “That is unlikely – it is more likely that we’ll have an answer in November and December.”

If that timing does come to pass, Dr. Fauci said, it’s possible that distribution of doses could start at the end of the year, continuing throughout the beginning and middle of 2021.

Although there are no guarantees, Dr. Fauci said he is “cautiously optimistic” regarding the timeline.

He said that his optimism is based in part on animal studies and phase 1 data that demonstrate robust neutralizing antibody responses to a vaccine that are equivalent to, if not greater than, natural infection with the SARS-CoV-2 virus that causes COVID-19.

Rapid development gives reason for hope

Ryan C. Maves, MD, FCCP, a critical care and infectious disease specialist at Naval Medical Center San Diego, said there is reason to be hopeful that a vaccine will be available by the end of the calendar year. He cautioned, however, that this timing is based on the assumption that one of the vaccines will be proven safe and effective very soon.

“We’re lucky to have multiple phase 3 trials using multiple vaccine technologies in different platforms,” Dr. Maves said in a panel discussion following Dr. Fauci’s remarks. “I think the odds are very high that one of them will be effective.”

“I’m hoping that multiple vaccines will be effective,” Dr. Maves added. “Then we’ll be in a good position of determining which is the best of several good options, as a society and as a world.”

COVID-19 vaccine development over the past year has been remarkably fast, especially given the previous record set by the mumps vaccine, which took about four years to go from initial steps to rollout, Dr. Maves noted.

Dr. Fauci said the federal government has taken a “strategic approach” to the COVID-19 vaccine that includes direct involvement in the research and development of six different vaccine candidates, five of which are now in phase 3 trials.

As part of that strategic approach, the study protocols are harmonized to have a common data and safety monitoring board, common primary and secondary endpoints, and an independent statistical group to determine correlates of protection, Dr. Fauci said.

Prioritizing COVID-19 vaccine distribution

Who gets COVID-19 vaccine first will be a challenge for governmental organizations as well as bioethicists, who have proposed different strategies for fairly prioritizing different groups for access.

Reaching communities of color will be an important consideration for prioritization, according to Dr. Maves, given the disproportionate burden of disease on Black and Hispanic individuals, among other such populations.

COVID-19–related hospitalization rates have been substantially higher in communities of color, Dr. Fauci said in his keynote address. Age-adjusted hospitalization rates for Hispanic/Latinx and Black populations are 375 to 368 per 100,000, respectively, compared with just 82 per 100,000 for White non-Hispanics, according to data from the Centers for Disease Control and Prevention.

Outreach to those communities should include building trust in those populations that they will benefit from a safe and effective vaccine, and making sure that the vaccine is available to those communities as quickly as possible, Dr. Maves said.

Dr. Fauci and Dr. Maves provided no disclosures related to their presentations.

[email protected]

A COVID-19 vaccine could be proven effective within the last months of 2020, with distribution of first doses possible before the end of the year, according to Anthony S. Fauci, MD, director, National Institute of Allergy and Infectious Diseases, Bethesda, Md.

“Given the rate of infection that’s going on in this country, and the distribution of the clinical trial sites involving tens of thousands of volunteers, we project that we will have an answer as to whether or not we have a safe and effective vaccine by November or December,” Dr. Fauci said today in his virtual keynote address during the annual meeting of the American College of Chest Physicians.

“It may come earlier -- this month, in October,” he added in his remarks. “That is unlikely – it is more likely that we’ll have an answer in November and December.”

If that timing does come to pass, Dr. Fauci said, it’s possible that distribution of doses could start at the end of the year, continuing throughout the beginning and middle of 2021.

Although there are no guarantees, Dr. Fauci said he is “cautiously optimistic” regarding the timeline.

He said that his optimism is based in part on animal studies and phase 1 data that demonstrate robust neutralizing antibody responses to a vaccine that are equivalent to, if not greater than, natural infection with the SARS-CoV-2 virus that causes COVID-19.

Rapid development gives reason for hope

Ryan C. Maves, MD, FCCP, a critical care and infectious disease specialist at Naval Medical Center San Diego, said there is reason to be hopeful that a vaccine will be available by the end of the calendar year. He cautioned, however, that this timing is based on the assumption that one of the vaccines will be proven safe and effective very soon.

“We’re lucky to have multiple phase 3 trials using multiple vaccine technologies in different platforms,” Dr. Maves said in a panel discussion following Dr. Fauci’s remarks. “I think the odds are very high that one of them will be effective.”

“I’m hoping that multiple vaccines will be effective,” Dr. Maves added. “Then we’ll be in a good position of determining which is the best of several good options, as a society and as a world.”

COVID-19 vaccine development over the past year has been remarkably fast, especially given the previous record set by the mumps vaccine, which took about four years to go from initial steps to rollout, Dr. Maves noted.

Dr. Fauci said the federal government has taken a “strategic approach” to the COVID-19 vaccine that includes direct involvement in the research and development of six different vaccine candidates, five of which are now in phase 3 trials.

As part of that strategic approach, the study protocols are harmonized to have a common data and safety monitoring board, common primary and secondary endpoints, and an independent statistical group to determine correlates of protection, Dr. Fauci said.

Prioritizing COVID-19 vaccine distribution

Who gets COVID-19 vaccine first will be a challenge for governmental organizations as well as bioethicists, who have proposed different strategies for fairly prioritizing different groups for access.

Reaching communities of color will be an important consideration for prioritization, according to Dr. Maves, given the disproportionate burden of disease on Black and Hispanic individuals, among other such populations.

COVID-19–related hospitalization rates have been substantially higher in communities of color, Dr. Fauci said in his keynote address. Age-adjusted hospitalization rates for Hispanic/Latinx and Black populations are 375 to 368 per 100,000, respectively, compared with just 82 per 100,000 for White non-Hispanics, according to data from the Centers for Disease Control and Prevention.

Outreach to those communities should include building trust in those populations that they will benefit from a safe and effective vaccine, and making sure that the vaccine is available to those communities as quickly as possible, Dr. Maves said.

Dr. Fauci and Dr. Maves provided no disclosures related to their presentations.

[email protected]

A COVID-19 vaccine could be proven effective within the last months of 2020, with distribution of first doses possible before the end of the year, according to Anthony S. Fauci, MD, director, National Institute of Allergy and Infectious Diseases, Bethesda, Md.

“Given the rate of infection that’s going on in this country, and the distribution of the clinical trial sites involving tens of thousands of volunteers, we project that we will have an answer as to whether or not we have a safe and effective vaccine by November or December,” Dr. Fauci said today in his virtual keynote address during the annual meeting of the American College of Chest Physicians.

“It may come earlier -- this month, in October,” he added in his remarks. “That is unlikely – it is more likely that we’ll have an answer in November and December.”

If that timing does come to pass, Dr. Fauci said, it’s possible that distribution of doses could start at the end of the year, continuing throughout the beginning and middle of 2021.

Although there are no guarantees, Dr. Fauci said he is “cautiously optimistic” regarding the timeline.

He said that his optimism is based in part on animal studies and phase 1 data that demonstrate robust neutralizing antibody responses to a vaccine that are equivalent to, if not greater than, natural infection with the SARS-CoV-2 virus that causes COVID-19.

Rapid development gives reason for hope

Ryan C. Maves, MD, FCCP, a critical care and infectious disease specialist at Naval Medical Center San Diego, said there is reason to be hopeful that a vaccine will be available by the end of the calendar year. He cautioned, however, that this timing is based on the assumption that one of the vaccines will be proven safe and effective very soon.

“We’re lucky to have multiple phase 3 trials using multiple vaccine technologies in different platforms,” Dr. Maves said in a panel discussion following Dr. Fauci’s remarks. “I think the odds are very high that one of them will be effective.”

“I’m hoping that multiple vaccines will be effective,” Dr. Maves added. “Then we’ll be in a good position of determining which is the best of several good options, as a society and as a world.”

COVID-19 vaccine development over the past year has been remarkably fast, especially given the previous record set by the mumps vaccine, which took about four years to go from initial steps to rollout, Dr. Maves noted.

Dr. Fauci said the federal government has taken a “strategic approach” to the COVID-19 vaccine that includes direct involvement in the research and development of six different vaccine candidates, five of which are now in phase 3 trials.

As part of that strategic approach, the study protocols are harmonized to have a common data and safety monitoring board, common primary and secondary endpoints, and an independent statistical group to determine correlates of protection, Dr. Fauci said.

Prioritizing COVID-19 vaccine distribution

Who gets COVID-19 vaccine first will be a challenge for governmental organizations as well as bioethicists, who have proposed different strategies for fairly prioritizing different groups for access.

Reaching communities of color will be an important consideration for prioritization, according to Dr. Maves, given the disproportionate burden of disease on Black and Hispanic individuals, among other such populations.

COVID-19–related hospitalization rates have been substantially higher in communities of color, Dr. Fauci said in his keynote address. Age-adjusted hospitalization rates for Hispanic/Latinx and Black populations are 375 to 368 per 100,000, respectively, compared with just 82 per 100,000 for White non-Hispanics, according to data from the Centers for Disease Control and Prevention.

Outreach to those communities should include building trust in those populations that they will benefit from a safe and effective vaccine, and making sure that the vaccine is available to those communities as quickly as possible, Dr. Maves said.

Dr. Fauci and Dr. Maves provided no disclosures related to their presentations.

[email protected]

For more information about upcoming events and award deadlines, please visit http://agau.gastro.org and http://www.gastro.org/research-funding.

UPCOMING EVENTS

Jan. 15-17, 2021
Gastrointestinal Cancers Symposium
Through an engaging lineup of novel science, education, and exhibits, the virtual 2021 Gastrointestinal (GI) Cancers Symposium offers new, innovative findings in GI cancer treatment, research, and care.
Early-bird deadline: Dec. 16, 2020.

Jan. 21-24, 2021
Crohn’s & Colitis Congress®Join health care professionals and researchers virtually at the Crohn’s & Colitis Congress^® for the premier conference on IBD. Discover different perspectives, practical information you can immediately implement, and potential treatments on the horizon.
Early-bird deadline: Friday, Nov. 6, 2020.

May 21-23, 2021
Digestive Disease Week^® (DDW)
Save the date for the world’s leading event in digestive disease. DDW^® brings professionals in gastroenterology, hepatology, endoscopy, and GI surgery together. Experience growth when you share your research, converge with trailblazers, and improve the lives of patients suffering from GI and liver diseases.
Abstract submission window Oct. 15 to Dec. 3, 2020.

AWARD DEADLINES

American Gastroenterological Association (AGA) Student Abstract Award
This $500 travel award supports recipients who are graduate students, medical students,or medical residents (residents up to postgraduate year 3) giving abstract-based oral or poster presentations at Digestive Disease Week^® (DDW). The top-scoring abstract will be designated the Student Abstract of the Year and receive a $1,000 award.
Application deadline: Feb. 24, 2021

AGA–Moti L. & Kamla Rustgi International Travel Awards
This $750 travel award provides support to early-career (that is, 35 years of age or younger at the time of DDW) basic, translational or clinical investigators residing outside North America to offset travel and related expenses to attend DDW.
Application deadline: Feb. 24, 2021

AGA Fellow Abstract Award
This $500 travel award supports recipients who are MD, PhD, or equivalent fellows giving abstract-based oral or poster presentations DDW. The top-scoring abstract will be designated the Fellow Abstract of the Year and receive a $1,000 award.
Application deadline: Feb. 24, 2021

For more information about upcoming events and award deadlines, please visit http://agau.gastro.org and http://www.gastro.org/research-funding.

UPCOMING EVENTS

Jan. 15-17, 2021
Gastrointestinal Cancers Symposium
Through an engaging lineup of novel science, education, and exhibits, the virtual 2021 Gastrointestinal (GI) Cancers Symposium offers new, innovative findings in GI cancer treatment, research, and care.
Early-bird deadline: Dec. 16, 2020.

Jan. 21-24, 2021
Crohn’s & Colitis Congress®Join health care professionals and researchers virtually at the Crohn’s & Colitis Congress^® for the premier conference on IBD. Discover different perspectives, practical information you can immediately implement, and potential treatments on the horizon.
Early-bird deadline: Friday, Nov. 6, 2020.

May 21-23, 2021
Digestive Disease Week^® (DDW)
Save the date for the world’s leading event in digestive disease. DDW^® brings professionals in gastroenterology, hepatology, endoscopy, and GI surgery together. Experience growth when you share your research, converge with trailblazers, and improve the lives of patients suffering from GI and liver diseases.
Abstract submission window Oct. 15 to Dec. 3, 2020.

AWARD DEADLINES

American Gastroenterological Association (AGA) Student Abstract Award
This $500 travel award supports recipients who are graduate students, medical students,or medical residents (residents up to postgraduate year 3) giving abstract-based oral or poster presentations at Digestive Disease Week^® (DDW). The top-scoring abstract will be designated the Student Abstract of the Year and receive a $1,000 award.
Application deadline: Feb. 24, 2021

AGA–Moti L. & Kamla Rustgi International Travel Awards
This $750 travel award provides support to early-career (that is, 35 years of age or younger at the time of DDW) basic, translational or clinical investigators residing outside North America to offset travel and related expenses to attend DDW.
Application deadline: Feb. 24, 2021

AGA Fellow Abstract Award
This $500 travel award supports recipients who are MD, PhD, or equivalent fellows giving abstract-based oral or poster presentations DDW. The top-scoring abstract will be designated the Fellow Abstract of the Year and receive a $1,000 award.
Application deadline: Feb. 24, 2021

For more information about upcoming events and award deadlines, please visit http://agau.gastro.org and http://www.gastro.org/research-funding.

UPCOMING EVENTS

Jan. 15-17, 2021
Gastrointestinal Cancers Symposium
Through an engaging lineup of novel science, education, and exhibits, the virtual 2021 Gastrointestinal (GI) Cancers Symposium offers new, innovative findings in GI cancer treatment, research, and care.
Early-bird deadline: Dec. 16, 2020.

Jan. 21-24, 2021
Crohn’s & Colitis Congress®Join health care professionals and researchers virtually at the Crohn’s & Colitis Congress^® for the premier conference on IBD. Discover different perspectives, practical information you can immediately implement, and potential treatments on the horizon.
Early-bird deadline: Friday, Nov. 6, 2020.

May 21-23, 2021
Digestive Disease Week^® (DDW)
Save the date for the world’s leading event in digestive disease. DDW^® brings professionals in gastroenterology, hepatology, endoscopy, and GI surgery together. Experience growth when you share your research, converge with trailblazers, and improve the lives of patients suffering from GI and liver diseases.
Abstract submission window Oct. 15 to Dec. 3, 2020.

AWARD DEADLINES

American Gastroenterological Association (AGA) Student Abstract Award
This $500 travel award supports recipients who are graduate students, medical students,or medical residents (residents up to postgraduate year 3) giving abstract-based oral or poster presentations at Digestive Disease Week^® (DDW). The top-scoring abstract will be designated the Student Abstract of the Year and receive a $1,000 award.
Application deadline: Feb. 24, 2021

AGA–Moti L. & Kamla Rustgi International Travel Awards
This $750 travel award provides support to early-career (that is, 35 years of age or younger at the time of DDW) basic, translational or clinical investigators residing outside North America to offset travel and related expenses to attend DDW.
Application deadline: Feb. 24, 2021

AGA Fellow Abstract Award
This $500 travel award supports recipients who are MD, PhD, or equivalent fellows giving abstract-based oral or poster presentations DDW. The top-scoring abstract will be designated the Fellow Abstract of the Year and receive a $1,000 award.
Application deadline: Feb. 24, 2021

Over half of surgeons who reported treating melanoma with Mohs micrographic surgery (MMS) are using the technique to treat invasive melanoma, according to a national cross-sectional survey of members of the American College of Mohs Surgery.

Of 513 survey participants, 40.9% reported using MMS to treat any subtype of melanoma. Most of these surgeons reported treating both lentigo maligna (97.5%) and other melanoma in situ (MIS) subtypes (91.4%). A slight majority – 58.6% – reported treating invasive T1 melanoma, and 20.5% reported treating invasive T2 and/or higher-stage melanoma with MMS.

The analysis, published in Dermatologic Surgery, was done by Spyros M. Siscos, MD, and a team of residents and faculty in the division of dermatology at the University of Kansas Medical Center, Kansas City.

It comes on the heels of an analysis of claims data for Mohs surgery, published last year in JAMA Dermatology, which showed a more than threefold increase in the use of Mohs surgery for melanoma from 2.6% of all surgical cases in 2001 to 7.9% in 2016.

With the increased use of MMS for treatment of melanoma, “Mohs surgeons who previously treated MIS with MMS may be increasingly doing so and/or expanding their scope of treatment to include invasive melanoma,” the University of Kansas investigators wrote.

That a slight majority now report treating invasive melanoma with MMS “may be due, in part, to upstaging during the MMS procedure and the increasing evidence demonstrating improved survival of early-invasive melanoma treated with MMS compared with [wide local excision],” as well as the advent of melanocytic immunohistochemical (IHC) stains, particularly melanoma antigen recognized by T-cells 1 (MART-1), they said. However, 29% of surveyed Mohs surgeons treating melanoma with MMS do not use IHC stains “despite growing evidence supporting” their use, the authors wrote.

The advent of IHC stains, particularly MART-1, has improved the accuracy of interpreting frozen sections of melanoma, they reported, noting that MMS without IHC has been associated with a recurrence rate as high as 33%. Of the 71% who reported using IHC stains, MART-1 was the primary IHC stain for virtually all of them (97.3%).

There was also variation in the number of surgeons who reported debulking MIS. Eighty-two percent take this approach, excising the clinically visible tumor before excising the initial Mohs stage – almost all with a scalpel. More than half of these surgeons – 58.5% – submit the entire debulked MIS specimen for permanent vertical sectioning (breadloafing) to evaluate for deeper tumor invasion.

The others reported submitting the entire debulked specimen for frozen vertical sectioning, or portions of the specimen for both permanent and frozen vertical sectioning. “It is unclear why a minority of surveyed Mohs surgeons reported not debulking MIS,” wrote Dr. Siscos and his colleagues.

The average margin size of the first Mohs stage for MIS was 4.96 ± 1.74 mm, which is at the lower end of the 0.5-1.0 cm range for wide local excision (WLE) recommended by the National Comprehensive Cancer Network (NCCN) and the American Academy of Dermatology (AAD), according to a clinical practice guideline. (The survey did not investigate initial margins for invasive melanoma treated with MMS.)

Jeremy R. Etzhorn, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and an author of a 2019 claims data analysis of excisional surgery practices for melanoma, said that the new survey findings – like the prior analysis – highlight the variability in approaches to using MMS for melanoma.

“Mohs for melanoma [seems] like a one-liner ... but really, there are [a lot] of different techniques that fall under that umbrella, if you parse out all the variations,” he said in an interview.

Per the 2016 claims analysis, he noted, IHC was used in less than 40% of Mohs surgery cases for melanoma, and there were wide geographic variations. “The biggest critique of Mohs surgery for melanoma over the last two decades has been that it’s hard to see the tumor,” he said. “But with the advent of IHC, that challenge was overcome.”

Surgical excision practices are evolving without the development of best practice guidelines, said Dr. Etzkorn, who is director of clinical research for the University of Pennsylvania dermatologic oncology center. Multisociety guidelines published in 2012 on appropriate use criteria for Mohs surgery do not offer specific recommendations on the use of MMS for invasive melanoma. Nor do guidelines from the AAD and the NCCN, he said.

“What this [new] study highlights and what’s being discussed amongst Moh’s surgeons” is that Mohs for melanoma “has be to be standardized” to some extent and then clinical trials conducted comparing Mohs to conventional excision. The studies that have been published in recent years comparing MMS with WLE for MIS and invasive melanoma are “not gold standard studies,” he said.

Practice guidelines then can be informed by high-quality evidence on its safety and efficacy, he said.

The 513 participants in the newly published survey represent a 31.5% response rate. Invasive T2 and/or higher stage melanoma was more likely to be treated with MMS in academic hospitals, compared with other practice settings (30.2% v. 18.1%), Dr. Siscos and his coauthors reported.

Participants who reported treating melanoma with MMS were more likely to report fellowship exposure and more likely to have received fellowship training on melanocytic IHC stains. The study “highlights the importance of fellowship exposure to MMS and IHC staining for melanoma,” the authors wrote, adding that postfellowship training opportunities in MMS and IHC staining for melanoma may help broaden its use among Mohs surgeons who received inadequate fellowship exposure.

Dr. Siscos and his colleagues reported no significant interest with commercial supporters. Dr. Etzkorn had no disclosures.

SOURCE: Siscos S et al. Dermatol Surg. 2020 Oct;46(10):1267-71.
 

Over half of surgeons who reported treating melanoma with Mohs micrographic surgery (MMS) are using the technique to treat invasive melanoma, according to a national cross-sectional survey of members of the American College of Mohs Surgery.

Of 513 survey participants, 40.9% reported using MMS to treat any subtype of melanoma. Most of these surgeons reported treating both lentigo maligna (97.5%) and other melanoma in situ (MIS) subtypes (91.4%). A slight majority – 58.6% – reported treating invasive T1 melanoma, and 20.5% reported treating invasive T2 and/or higher-stage melanoma with MMS.

The analysis, published in Dermatologic Surgery, was done by Spyros M. Siscos, MD, and a team of residents and faculty in the division of dermatology at the University of Kansas Medical Center, Kansas City.

It comes on the heels of an analysis of claims data for Mohs surgery, published last year in JAMA Dermatology, which showed a more than threefold increase in the use of Mohs surgery for melanoma from 2.6% of all surgical cases in 2001 to 7.9% in 2016.

With the increased use of MMS for treatment of melanoma, “Mohs surgeons who previously treated MIS with MMS may be increasingly doing so and/or expanding their scope of treatment to include invasive melanoma,” the University of Kansas investigators wrote.

That a slight majority now report treating invasive melanoma with MMS “may be due, in part, to upstaging during the MMS procedure and the increasing evidence demonstrating improved survival of early-invasive melanoma treated with MMS compared with [wide local excision],” as well as the advent of melanocytic immunohistochemical (IHC) stains, particularly melanoma antigen recognized by T-cells 1 (MART-1), they said. However, 29% of surveyed Mohs surgeons treating melanoma with MMS do not use IHC stains “despite growing evidence supporting” their use, the authors wrote.

The advent of IHC stains, particularly MART-1, has improved the accuracy of interpreting frozen sections of melanoma, they reported, noting that MMS without IHC has been associated with a recurrence rate as high as 33%. Of the 71% who reported using IHC stains, MART-1 was the primary IHC stain for virtually all of them (97.3%).

There was also variation in the number of surgeons who reported debulking MIS. Eighty-two percent take this approach, excising the clinically visible tumor before excising the initial Mohs stage – almost all with a scalpel. More than half of these surgeons – 58.5% – submit the entire debulked MIS specimen for permanent vertical sectioning (breadloafing) to evaluate for deeper tumor invasion.

The others reported submitting the entire debulked specimen for frozen vertical sectioning, or portions of the specimen for both permanent and frozen vertical sectioning. “It is unclear why a minority of surveyed Mohs surgeons reported not debulking MIS,” wrote Dr. Siscos and his colleagues.

The average margin size of the first Mohs stage for MIS was 4.96 ± 1.74 mm, which is at the lower end of the 0.5-1.0 cm range for wide local excision (WLE) recommended by the National Comprehensive Cancer Network (NCCN) and the American Academy of Dermatology (AAD), according to a clinical practice guideline. (The survey did not investigate initial margins for invasive melanoma treated with MMS.)

Jeremy R. Etzhorn, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and an author of a 2019 claims data analysis of excisional surgery practices for melanoma, said that the new survey findings – like the prior analysis – highlight the variability in approaches to using MMS for melanoma.

“Mohs for melanoma [seems] like a one-liner ... but really, there are [a lot] of different techniques that fall under that umbrella, if you parse out all the variations,” he said in an interview.

Per the 2016 claims analysis, he noted, IHC was used in less than 40% of Mohs surgery cases for melanoma, and there were wide geographic variations. “The biggest critique of Mohs surgery for melanoma over the last two decades has been that it’s hard to see the tumor,” he said. “But with the advent of IHC, that challenge was overcome.”

Surgical excision practices are evolving without the development of best practice guidelines, said Dr. Etzkorn, who is director of clinical research for the University of Pennsylvania dermatologic oncology center. Multisociety guidelines published in 2012 on appropriate use criteria for Mohs surgery do not offer specific recommendations on the use of MMS for invasive melanoma. Nor do guidelines from the AAD and the NCCN, he said.

“What this [new] study highlights and what’s being discussed amongst Moh’s surgeons” is that Mohs for melanoma “has be to be standardized” to some extent and then clinical trials conducted comparing Mohs to conventional excision. The studies that have been published in recent years comparing MMS with WLE for MIS and invasive melanoma are “not gold standard studies,” he said.

Practice guidelines then can be informed by high-quality evidence on its safety and efficacy, he said.

The 513 participants in the newly published survey represent a 31.5% response rate. Invasive T2 and/or higher stage melanoma was more likely to be treated with MMS in academic hospitals, compared with other practice settings (30.2% v. 18.1%), Dr. Siscos and his coauthors reported.

Participants who reported treating melanoma with MMS were more likely to report fellowship exposure and more likely to have received fellowship training on melanocytic IHC stains. The study “highlights the importance of fellowship exposure to MMS and IHC staining for melanoma,” the authors wrote, adding that postfellowship training opportunities in MMS and IHC staining for melanoma may help broaden its use among Mohs surgeons who received inadequate fellowship exposure.

Dr. Siscos and his colleagues reported no significant interest with commercial supporters. Dr. Etzkorn had no disclosures.

SOURCE: Siscos S et al. Dermatol Surg. 2020 Oct;46(10):1267-71.
 

Over half of surgeons who reported treating melanoma with Mohs micrographic surgery (MMS) are using the technique to treat invasive melanoma, according to a national cross-sectional survey of members of the American College of Mohs Surgery.

Of 513 survey participants, 40.9% reported using MMS to treat any subtype of melanoma. Most of these surgeons reported treating both lentigo maligna (97.5%) and other melanoma in situ (MIS) subtypes (91.4%). A slight majority – 58.6% – reported treating invasive T1 melanoma, and 20.5% reported treating invasive T2 and/or higher-stage melanoma with MMS.

The analysis, published in Dermatologic Surgery, was done by Spyros M. Siscos, MD, and a team of residents and faculty in the division of dermatology at the University of Kansas Medical Center, Kansas City.

It comes on the heels of an analysis of claims data for Mohs surgery, published last year in JAMA Dermatology, which showed a more than threefold increase in the use of Mohs surgery for melanoma from 2.6% of all surgical cases in 2001 to 7.9% in 2016.

With the increased use of MMS for treatment of melanoma, “Mohs surgeons who previously treated MIS with MMS may be increasingly doing so and/or expanding their scope of treatment to include invasive melanoma,” the University of Kansas investigators wrote.

That a slight majority now report treating invasive melanoma with MMS “may be due, in part, to upstaging during the MMS procedure and the increasing evidence demonstrating improved survival of early-invasive melanoma treated with MMS compared with [wide local excision],” as well as the advent of melanocytic immunohistochemical (IHC) stains, particularly melanoma antigen recognized by T-cells 1 (MART-1), they said. However, 29% of surveyed Mohs surgeons treating melanoma with MMS do not use IHC stains “despite growing evidence supporting” their use, the authors wrote.

The advent of IHC stains, particularly MART-1, has improved the accuracy of interpreting frozen sections of melanoma, they reported, noting that MMS without IHC has been associated with a recurrence rate as high as 33%. Of the 71% who reported using IHC stains, MART-1 was the primary IHC stain for virtually all of them (97.3%).

There was also variation in the number of surgeons who reported debulking MIS. Eighty-two percent take this approach, excising the clinically visible tumor before excising the initial Mohs stage – almost all with a scalpel. More than half of these surgeons – 58.5% – submit the entire debulked MIS specimen for permanent vertical sectioning (breadloafing) to evaluate for deeper tumor invasion.

The others reported submitting the entire debulked specimen for frozen vertical sectioning, or portions of the specimen for both permanent and frozen vertical sectioning. “It is unclear why a minority of surveyed Mohs surgeons reported not debulking MIS,” wrote Dr. Siscos and his colleagues.

The average margin size of the first Mohs stage for MIS was 4.96 ± 1.74 mm, which is at the lower end of the 0.5-1.0 cm range for wide local excision (WLE) recommended by the National Comprehensive Cancer Network (NCCN) and the American Academy of Dermatology (AAD), according to a clinical practice guideline. (The survey did not investigate initial margins for invasive melanoma treated with MMS.)

Jeremy R. Etzhorn, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and an author of a 2019 claims data analysis of excisional surgery practices for melanoma, said that the new survey findings – like the prior analysis – highlight the variability in approaches to using MMS for melanoma.

“Mohs for melanoma [seems] like a one-liner ... but really, there are [a lot] of different techniques that fall under that umbrella, if you parse out all the variations,” he said in an interview.

Per the 2016 claims analysis, he noted, IHC was used in less than 40% of Mohs surgery cases for melanoma, and there were wide geographic variations. “The biggest critique of Mohs surgery for melanoma over the last two decades has been that it’s hard to see the tumor,” he said. “But with the advent of IHC, that challenge was overcome.”

Surgical excision practices are evolving without the development of best practice guidelines, said Dr. Etzkorn, who is director of clinical research for the University of Pennsylvania dermatologic oncology center. Multisociety guidelines published in 2012 on appropriate use criteria for Mohs surgery do not offer specific recommendations on the use of MMS for invasive melanoma. Nor do guidelines from the AAD and the NCCN, he said.

“What this [new] study highlights and what’s being discussed amongst Moh’s surgeons” is that Mohs for melanoma “has be to be standardized” to some extent and then clinical trials conducted comparing Mohs to conventional excision. The studies that have been published in recent years comparing MMS with WLE for MIS and invasive melanoma are “not gold standard studies,” he said.

Practice guidelines then can be informed by high-quality evidence on its safety and efficacy, he said.

The 513 participants in the newly published survey represent a 31.5% response rate. Invasive T2 and/or higher stage melanoma was more likely to be treated with MMS in academic hospitals, compared with other practice settings (30.2% v. 18.1%), Dr. Siscos and his coauthors reported.

Participants who reported treating melanoma with MMS were more likely to report fellowship exposure and more likely to have received fellowship training on melanocytic IHC stains. The study “highlights the importance of fellowship exposure to MMS and IHC staining for melanoma,” the authors wrote, adding that postfellowship training opportunities in MMS and IHC staining for melanoma may help broaden its use among Mohs surgeons who received inadequate fellowship exposure.

Dr. Siscos and his colleagues reported no significant interest with commercial supporters. Dr. Etzkorn had no disclosures.

SOURCE: Siscos S et al. Dermatol Surg. 2020 Oct;46(10):1267-71.
 

The recall of extended-release metformin continues this month as 76 more lots have been flagged for a possible cancer-causing ingredient.

The Food and Drug Administration announced the latest recall, involving Marksans Pharma Limited and Sun Pharmaceutical Industries products, on Oct. 5. It involves the 500-mg and 700-mg tablets. More than 175 different drug combinations have been recalled since late May.

Consumers can see all the recalled metformin products at this FDA website. The agency says that immediate-release metformin does not appear to have the same contamination problem.

The FDA has been investigating the presence of nitrosamines, known to be possible carcinogens, in the popular diabetes medications since December, when they were first discovered in drugs in other countries. The agency said this month they still do not know the source of nitrosamines in the medications.

The investigation and subsequent recalls follow similar ones for contamination of popular heartburn and blood pressure drugs also for nitrosamines, such as N-Nitrosodimethylamine (NDMA).

The FDA says patients taking metformin products that have been recalled should continue taking the medication until a doctor or pharmacist gives them a replacement or a different treatment option. It could be dangerous for patients with type 2 diabetes to stop taking the medication without first talking to their doctor.

The agency has asked drug manufacturers to test products before batches are released into the market. The companies must tell the FDA if any product shows levels of nitrosamines above the acceptable limit.

The risk from nitrosamines is not clear. The FDA says they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”
 

This article first appeared on WebMD.com.

The recall of extended-release metformin continues this month as 76 more lots have been flagged for a possible cancer-causing ingredient.

The Food and Drug Administration announced the latest recall, involving Marksans Pharma Limited and Sun Pharmaceutical Industries products, on Oct. 5. It involves the 500-mg and 700-mg tablets. More than 175 different drug combinations have been recalled since late May.

Consumers can see all the recalled metformin products at this FDA website. The agency says that immediate-release metformin does not appear to have the same contamination problem.

The FDA has been investigating the presence of nitrosamines, known to be possible carcinogens, in the popular diabetes medications since December, when they were first discovered in drugs in other countries. The agency said this month they still do not know the source of nitrosamines in the medications.

The investigation and subsequent recalls follow similar ones for contamination of popular heartburn and blood pressure drugs also for nitrosamines, such as N-Nitrosodimethylamine (NDMA).

The FDA says patients taking metformin products that have been recalled should continue taking the medication until a doctor or pharmacist gives them a replacement or a different treatment option. It could be dangerous for patients with type 2 diabetes to stop taking the medication without first talking to their doctor.

The agency has asked drug manufacturers to test products before batches are released into the market. The companies must tell the FDA if any product shows levels of nitrosamines above the acceptable limit.

The risk from nitrosamines is not clear. The FDA says they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”
 

This article first appeared on WebMD.com.

The recall of extended-release metformin continues this month as 76 more lots have been flagged for a possible cancer-causing ingredient.

The Food and Drug Administration announced the latest recall, involving Marksans Pharma Limited and Sun Pharmaceutical Industries products, on Oct. 5. It involves the 500-mg and 700-mg tablets. More than 175 different drug combinations have been recalled since late May.

Consumers can see all the recalled metformin products at this FDA website. The agency says that immediate-release metformin does not appear to have the same contamination problem.

The FDA has been investigating the presence of nitrosamines, known to be possible carcinogens, in the popular diabetes medications since December, when they were first discovered in drugs in other countries. The agency said this month they still do not know the source of nitrosamines in the medications.

The investigation and subsequent recalls follow similar ones for contamination of popular heartburn and blood pressure drugs also for nitrosamines, such as N-Nitrosodimethylamine (NDMA).

The FDA says patients taking metformin products that have been recalled should continue taking the medication until a doctor or pharmacist gives them a replacement or a different treatment option. It could be dangerous for patients with type 2 diabetes to stop taking the medication without first talking to their doctor.

The agency has asked drug manufacturers to test products before batches are released into the market. The companies must tell the FDA if any product shows levels of nitrosamines above the acceptable limit.

The risk from nitrosamines is not clear. The FDA says they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”
 

This article first appeared on WebMD.com.

Budesonide orodispersible tablets maintained remissions of eosinophilic esophagitis for 48 weeks in approximately 75% of patients and did not increase the risk for most adverse events, compared with placebo, according to the findings of a multicenter, randomized, double-blind trial.

While prior studies have shown that swallowed topical corticosteroids such as budesonide or fluticasone induce remission in EoE, this is the first multicenter phase 3 study of budesonide orodispersible tablets (BOTs) for maintaining remissions over the long term, wrote Alex Straumann, MD, of the Swiss EoE Research Group and University Hospital Zurich, and associates in Gastroenterology.

Eosinophilic esophagitis is the most common cause of esophageal dysphagia and food impaction. Swallowed topical corticosteroids improve symptoms and inflammation, but the off-label use of formulations developed for airway administration in asthma shows “suboptimal esophageal targeting and efficacy,” the researchers wrote. In the phase 3 EOS-2 trial, twice-daily treatment with 1.0 mg BOTs had induced clinicohistologic remissions in 58% of adults with EoE at 6 weeks and in 85% at 12 weeks.

To study long-term maintenance BOT therapy, the researchers randomly assigned 204 of the remitted patients to 48 weeks of twice-daily BOT 0.5 mg, BOT 1.0 mg, or placebo. There were 68 patients per group. A total of 141 patients completed this double-blind phase, but all 204 were evaluable for the primary analysis. The primary outcome was remission at week 48, defined as freedom from relapse (dysphagia or odynophagia rated as 4 or higher on a 10-point numeric rating scale), histologic relapse (≥48 eosinophils per mm² high-power field), food impaction requiring endoscopic intervention, and dilation.

After 48 weeks, 51 patients in the 1-mg group (75%) and 50 patients in the 0.5-mg group (73.5%) remained in remission, compared with only three patients in the placebo group (4.4%; both P less than .0001). Patients in the placebo group relapsed after a median of 87 days off BOTs. Overall, BOT therapy was similarly efficacious regardless of factors such as history of allergic diseases, location of inflammation at the start of induction, or concomitant use of proton pump inhibitors. However, patients with inflammation of all three esophageal segments achieved “clinically relevant” greater rates of remission with twice-daily 1.0-mg BOT, compared with twice-daily 0.5-mg BOT (80% vs. 68%). In secondary analyses, rates of histologic relapse were 13.2% with 0.5-mg BOT twice daily, 10.3% with 1.0-mg BOT twice daily, and 90% with placebo, and rates of clinical relapse were 10.3%, 7.4%, and 60.3%, respectively. “Histological remission in the BOT 0.5 and 1.0mg twice daily group was independently maintained in all esophageal segments,” the researchers reported.

Rates of most adverse events were similar across treatment groups, and no serious treatment-emergent adverse events were reported. Average morning serum cortisol levels were similar among groups and did not change after treatment ended, but four patients on BOT therapy developed asymptomatic subnormal levels of morning cortisol. “Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5mg group and in 11.8% of patients in the BOT 1.0mg group; all infections resolved with treatment,” the researchers wrote.

The study and editorial support were funded by Dr. Falk Pharma GmbH, a pharmaceutical company in Germany. Dr. Falk Pharma was involved in the study design and data collection, analysis, and interpretation. Dr. Straumann disclosed fees from several pharmaceutical companies, including Dr. Falk Pharma and AstraZeneca, which makes budesonide. Several other coinvestigators also disclosed ties to Dr. Falk Pharma, AstraZeneca, and other pharmaceutical companies.

SOURCE: Straumann A et al. Gastroenterology. 2020 July 25. doi: 10.1053/j.gastro.2020.07.039.

Budesonide orodispersible tablets maintained remissions of eosinophilic esophagitis for 48 weeks in approximately 75% of patients and did not increase the risk for most adverse events, compared with placebo, according to the findings of a multicenter, randomized, double-blind trial.

While prior studies have shown that swallowed topical corticosteroids such as budesonide or fluticasone induce remission in EoE, this is the first multicenter phase 3 study of budesonide orodispersible tablets (BOTs) for maintaining remissions over the long term, wrote Alex Straumann, MD, of the Swiss EoE Research Group and University Hospital Zurich, and associates in Gastroenterology.

Eosinophilic esophagitis is the most common cause of esophageal dysphagia and food impaction. Swallowed topical corticosteroids improve symptoms and inflammation, but the off-label use of formulations developed for airway administration in asthma shows “suboptimal esophageal targeting and efficacy,” the researchers wrote. In the phase 3 EOS-2 trial, twice-daily treatment with 1.0 mg BOTs had induced clinicohistologic remissions in 58% of adults with EoE at 6 weeks and in 85% at 12 weeks.

To study long-term maintenance BOT therapy, the researchers randomly assigned 204 of the remitted patients to 48 weeks of twice-daily BOT 0.5 mg, BOT 1.0 mg, or placebo. There were 68 patients per group. A total of 141 patients completed this double-blind phase, but all 204 were evaluable for the primary analysis. The primary outcome was remission at week 48, defined as freedom from relapse (dysphagia or odynophagia rated as 4 or higher on a 10-point numeric rating scale), histologic relapse (≥48 eosinophils per mm² high-power field), food impaction requiring endoscopic intervention, and dilation.

After 48 weeks, 51 patients in the 1-mg group (75%) and 50 patients in the 0.5-mg group (73.5%) remained in remission, compared with only three patients in the placebo group (4.4%; both P less than .0001). Patients in the placebo group relapsed after a median of 87 days off BOTs. Overall, BOT therapy was similarly efficacious regardless of factors such as history of allergic diseases, location of inflammation at the start of induction, or concomitant use of proton pump inhibitors. However, patients with inflammation of all three esophageal segments achieved “clinically relevant” greater rates of remission with twice-daily 1.0-mg BOT, compared with twice-daily 0.5-mg BOT (80% vs. 68%). In secondary analyses, rates of histologic relapse were 13.2% with 0.5-mg BOT twice daily, 10.3% with 1.0-mg BOT twice daily, and 90% with placebo, and rates of clinical relapse were 10.3%, 7.4%, and 60.3%, respectively. “Histological remission in the BOT 0.5 and 1.0mg twice daily group was independently maintained in all esophageal segments,” the researchers reported.

Rates of most adverse events were similar across treatment groups, and no serious treatment-emergent adverse events were reported. Average morning serum cortisol levels were similar among groups and did not change after treatment ended, but four patients on BOT therapy developed asymptomatic subnormal levels of morning cortisol. “Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5mg group and in 11.8% of patients in the BOT 1.0mg group; all infections resolved with treatment,” the researchers wrote.

The study and editorial support were funded by Dr. Falk Pharma GmbH, a pharmaceutical company in Germany. Dr. Falk Pharma was involved in the study design and data collection, analysis, and interpretation. Dr. Straumann disclosed fees from several pharmaceutical companies, including Dr. Falk Pharma and AstraZeneca, which makes budesonide. Several other coinvestigators also disclosed ties to Dr. Falk Pharma, AstraZeneca, and other pharmaceutical companies.

SOURCE: Straumann A et al. Gastroenterology. 2020 July 25. doi: 10.1053/j.gastro.2020.07.039.

Budesonide orodispersible tablets maintained remissions of eosinophilic esophagitis for 48 weeks in approximately 75% of patients and did not increase the risk for most adverse events, compared with placebo, according to the findings of a multicenter, randomized, double-blind trial.

While prior studies have shown that swallowed topical corticosteroids such as budesonide or fluticasone induce remission in EoE, this is the first multicenter phase 3 study of budesonide orodispersible tablets (BOTs) for maintaining remissions over the long term, wrote Alex Straumann, MD, of the Swiss EoE Research Group and University Hospital Zurich, and associates in Gastroenterology.

Eosinophilic esophagitis is the most common cause of esophageal dysphagia and food impaction. Swallowed topical corticosteroids improve symptoms and inflammation, but the off-label use of formulations developed for airway administration in asthma shows “suboptimal esophageal targeting and efficacy,” the researchers wrote. In the phase 3 EOS-2 trial, twice-daily treatment with 1.0 mg BOTs had induced clinicohistologic remissions in 58% of adults with EoE at 6 weeks and in 85% at 12 weeks.

To study long-term maintenance BOT therapy, the researchers randomly assigned 204 of the remitted patients to 48 weeks of twice-daily BOT 0.5 mg, BOT 1.0 mg, or placebo. There were 68 patients per group. A total of 141 patients completed this double-blind phase, but all 204 were evaluable for the primary analysis. The primary outcome was remission at week 48, defined as freedom from relapse (dysphagia or odynophagia rated as 4 or higher on a 10-point numeric rating scale), histologic relapse (≥48 eosinophils per mm² high-power field), food impaction requiring endoscopic intervention, and dilation.

After 48 weeks, 51 patients in the 1-mg group (75%) and 50 patients in the 0.5-mg group (73.5%) remained in remission, compared with only three patients in the placebo group (4.4%; both P less than .0001). Patients in the placebo group relapsed after a median of 87 days off BOTs. Overall, BOT therapy was similarly efficacious regardless of factors such as history of allergic diseases, location of inflammation at the start of induction, or concomitant use of proton pump inhibitors. However, patients with inflammation of all three esophageal segments achieved “clinically relevant” greater rates of remission with twice-daily 1.0-mg BOT, compared with twice-daily 0.5-mg BOT (80% vs. 68%). In secondary analyses, rates of histologic relapse were 13.2% with 0.5-mg BOT twice daily, 10.3% with 1.0-mg BOT twice daily, and 90% with placebo, and rates of clinical relapse were 10.3%, 7.4%, and 60.3%, respectively. “Histological remission in the BOT 0.5 and 1.0mg twice daily group was independently maintained in all esophageal segments,” the researchers reported.

Rates of most adverse events were similar across treatment groups, and no serious treatment-emergent adverse events were reported. Average morning serum cortisol levels were similar among groups and did not change after treatment ended, but four patients on BOT therapy developed asymptomatic subnormal levels of morning cortisol. “Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5mg group and in 11.8% of patients in the BOT 1.0mg group; all infections resolved with treatment,” the researchers wrote.

The study and editorial support were funded by Dr. Falk Pharma GmbH, a pharmaceutical company in Germany. Dr. Falk Pharma was involved in the study design and data collection, analysis, and interpretation. Dr. Straumann disclosed fees from several pharmaceutical companies, including Dr. Falk Pharma and AstraZeneca, which makes budesonide. Several other coinvestigators also disclosed ties to Dr. Falk Pharma, AstraZeneca, and other pharmaceutical companies.

SOURCE: Straumann A et al. Gastroenterology. 2020 July 25. doi: 10.1053/j.gastro.2020.07.039.