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Applications for the CUTIS 2021 Resident Corner Column
The Cutis Editorial Board is now accepting applications for the 2021 Resident Corner column. The Editorial Board will select 2 to 3 residents to serve as the Resident Corner columnists for 1 year. Articles are posted online only at www.mdedge.com/dermatology but will be referenced in Index Medicus. All applicants must be current residents and will be in residency throughout 2021.
Columnists also will participate in a monthly resident takeover of our Dermatology Weekly podcast.
For consideration, send your curriculum vitae along with a brief (not to exceed 500 words) statement of why you enjoy Cutis and what you can offer your fellow residents in contributing a monthly column.
A signed letter of recommendation from the Director of the dermatology residency program also should be supplied.
All materials should be submitted via email to Melissa Sears ([email protected]) by October 15. The residents who are selected to write the column for the upcoming year will be notified by November 2.
We look forward to continuing to educate dermatology residents on topics that are most important to them!
The Cutis Editorial Board is now accepting applications for the 2021 Resident Corner column. The Editorial Board will select 2 to 3 residents to serve as the Resident Corner columnists for 1 year. Articles are posted online only at www.mdedge.com/dermatology but will be referenced in Index Medicus. All applicants must be current residents and will be in residency throughout 2021.
Columnists also will participate in a monthly resident takeover of our Dermatology Weekly podcast.
For consideration, send your curriculum vitae along with a brief (not to exceed 500 words) statement of why you enjoy Cutis and what you can offer your fellow residents in contributing a monthly column.
A signed letter of recommendation from the Director of the dermatology residency program also should be supplied.
All materials should be submitted via email to Melissa Sears ([email protected]) by October 15. The residents who are selected to write the column for the upcoming year will be notified by November 2.
We look forward to continuing to educate dermatology residents on topics that are most important to them!
The Cutis Editorial Board is now accepting applications for the 2021 Resident Corner column. The Editorial Board will select 2 to 3 residents to serve as the Resident Corner columnists for 1 year. Articles are posted online only at www.mdedge.com/dermatology but will be referenced in Index Medicus. All applicants must be current residents and will be in residency throughout 2021.
Columnists also will participate in a monthly resident takeover of our Dermatology Weekly podcast.
For consideration, send your curriculum vitae along with a brief (not to exceed 500 words) statement of why you enjoy Cutis and what you can offer your fellow residents in contributing a monthly column.
A signed letter of recommendation from the Director of the dermatology residency program also should be supplied.
All materials should be submitted via email to Melissa Sears ([email protected]) by October 15. The residents who are selected to write the column for the upcoming year will be notified by November 2.
We look forward to continuing to educate dermatology residents on topics that are most important to them!
How can hospitalists address health disparities for LGBTQ+ patients?
It is well established that lesbian, gay, bisexual, transgender, and queer (LGBTQ) patients suffer worse health outcomes, relative to patients who are heterosexual and cisgender – that is, those whose sense of personal identity and gender corresponds with their birth sex. The reasons for these disparities are multifactorial but include discrimination and limited provider knowledge about LGBTQ-specific health concerns.
These disparities – and what hospitalists can do to try to ameliorate them on the job – will be explored in a session at HM20 Virtual, “When the Answers Aren’t Straight Forward: Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ) Health Updates for the Hospitalist.”
, according to Tyler Anstett, DO, copresenter and assistant professor in the division of hospital medicine at the University of Colorado. He and copresenter Keshav Khanijow, MD, an assistant professor in the division of hospital medicine, Northwestern University, Chicago, will share results from the Q-HEALTH (Quantifying Hospitalist Education and Awareness of LGBTQ Topics in Health) national survey of SHM members about their knowledge and attitudes regarding LGBTQ health. This survey, sponsored by SHM’s Education Committee, identified knowledge and comfort gaps in caring for LGBTQ+ patients. Most respondents say they are interested in receiving more didactic training on this topic, building on an introductory session on LGBTQ+ health presented at last year’s SHM Annual Conference. They also named the Annual Conference as one of their top venues for receiving such training.
The session at HM20 Virtual will cover the health disparities identified in LGBTQ+ populations, with case examples that highlight those disparities, Dr. Anstett said. “We will review results from Q-HEALTH, the SHM-wide survey on provider attitudes, knowledge, and comfort in caring for LGBTQ+ patients. Finally, the session will cover basic LGBTQ+ terminology and, through clinical scenarios, provide attendees with some basic skills for improving their practice for LGBTQ+ patients.”
With over 11 million Americans who identify as lesbian, gay, bisexual, transgender, and/or queer, hospitalists will certainly encounter patients of diverse sexual orientations and gender identities, Dr. Anstett said. Hospitalists should serve as allies for their patients, including for those who are LGBTQ+. Through this session, attendees can reflect on individual practice and learn how to educate others on LGBTQ+ health basics.
“We hope the cases we present will provide attendees with an introduction to the health issues the LGBTQ+ community faces with greater prevalence, and what hospitalists can be thinking about when they approach these issues,” Dr. Khanijow added.
Dr. Anstett and Dr. Khanijow had no relevant financial conflicts to disclose.
When the Answers Aren’t Straight Forward: Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ) Health Updates for the Hospitalist
It is well established that lesbian, gay, bisexual, transgender, and queer (LGBTQ) patients suffer worse health outcomes, relative to patients who are heterosexual and cisgender – that is, those whose sense of personal identity and gender corresponds with their birth sex. The reasons for these disparities are multifactorial but include discrimination and limited provider knowledge about LGBTQ-specific health concerns.
These disparities – and what hospitalists can do to try to ameliorate them on the job – will be explored in a session at HM20 Virtual, “When the Answers Aren’t Straight Forward: Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ) Health Updates for the Hospitalist.”
, according to Tyler Anstett, DO, copresenter and assistant professor in the division of hospital medicine at the University of Colorado. He and copresenter Keshav Khanijow, MD, an assistant professor in the division of hospital medicine, Northwestern University, Chicago, will share results from the Q-HEALTH (Quantifying Hospitalist Education and Awareness of LGBTQ Topics in Health) national survey of SHM members about their knowledge and attitudes regarding LGBTQ health. This survey, sponsored by SHM’s Education Committee, identified knowledge and comfort gaps in caring for LGBTQ+ patients. Most respondents say they are interested in receiving more didactic training on this topic, building on an introductory session on LGBTQ+ health presented at last year’s SHM Annual Conference. They also named the Annual Conference as one of their top venues for receiving such training.
The session at HM20 Virtual will cover the health disparities identified in LGBTQ+ populations, with case examples that highlight those disparities, Dr. Anstett said. “We will review results from Q-HEALTH, the SHM-wide survey on provider attitudes, knowledge, and comfort in caring for LGBTQ+ patients. Finally, the session will cover basic LGBTQ+ terminology and, through clinical scenarios, provide attendees with some basic skills for improving their practice for LGBTQ+ patients.”
With over 11 million Americans who identify as lesbian, gay, bisexual, transgender, and/or queer, hospitalists will certainly encounter patients of diverse sexual orientations and gender identities, Dr. Anstett said. Hospitalists should serve as allies for their patients, including for those who are LGBTQ+. Through this session, attendees can reflect on individual practice and learn how to educate others on LGBTQ+ health basics.
“We hope the cases we present will provide attendees with an introduction to the health issues the LGBTQ+ community faces with greater prevalence, and what hospitalists can be thinking about when they approach these issues,” Dr. Khanijow added.
Dr. Anstett and Dr. Khanijow had no relevant financial conflicts to disclose.
When the Answers Aren’t Straight Forward: Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ) Health Updates for the Hospitalist
It is well established that lesbian, gay, bisexual, transgender, and queer (LGBTQ) patients suffer worse health outcomes, relative to patients who are heterosexual and cisgender – that is, those whose sense of personal identity and gender corresponds with their birth sex. The reasons for these disparities are multifactorial but include discrimination and limited provider knowledge about LGBTQ-specific health concerns.
These disparities – and what hospitalists can do to try to ameliorate them on the job – will be explored in a session at HM20 Virtual, “When the Answers Aren’t Straight Forward: Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ) Health Updates for the Hospitalist.”
, according to Tyler Anstett, DO, copresenter and assistant professor in the division of hospital medicine at the University of Colorado. He and copresenter Keshav Khanijow, MD, an assistant professor in the division of hospital medicine, Northwestern University, Chicago, will share results from the Q-HEALTH (Quantifying Hospitalist Education and Awareness of LGBTQ Topics in Health) national survey of SHM members about their knowledge and attitudes regarding LGBTQ health. This survey, sponsored by SHM’s Education Committee, identified knowledge and comfort gaps in caring for LGBTQ+ patients. Most respondents say they are interested in receiving more didactic training on this topic, building on an introductory session on LGBTQ+ health presented at last year’s SHM Annual Conference. They also named the Annual Conference as one of their top venues for receiving such training.
The session at HM20 Virtual will cover the health disparities identified in LGBTQ+ populations, with case examples that highlight those disparities, Dr. Anstett said. “We will review results from Q-HEALTH, the SHM-wide survey on provider attitudes, knowledge, and comfort in caring for LGBTQ+ patients. Finally, the session will cover basic LGBTQ+ terminology and, through clinical scenarios, provide attendees with some basic skills for improving their practice for LGBTQ+ patients.”
With over 11 million Americans who identify as lesbian, gay, bisexual, transgender, and/or queer, hospitalists will certainly encounter patients of diverse sexual orientations and gender identities, Dr. Anstett said. Hospitalists should serve as allies for their patients, including for those who are LGBTQ+. Through this session, attendees can reflect on individual practice and learn how to educate others on LGBTQ+ health basics.
“We hope the cases we present will provide attendees with an introduction to the health issues the LGBTQ+ community faces with greater prevalence, and what hospitalists can be thinking about when they approach these issues,” Dr. Khanijow added.
Dr. Anstett and Dr. Khanijow had no relevant financial conflicts to disclose.
When the Answers Aren’t Straight Forward: Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ) Health Updates for the Hospitalist
Early recognition of oncologic emergencies deemed ‘crucial’
During an oncologic emergency, making a clinical decision during the early diagnostic period is one of the most critical things a hospitalist can do when caring for patients with cancer. Hospitalists may not always be well versed in the symptoms of oncologic emergencies, though, particularly with newer treatments like immunotherapy and targeted therapies. They also may be tempted to contact colleagues in oncology when they may be qualified to handle these emergencies on their own.
At the end of her question-and-answer session, “Getting to Know Oncology Emergencies: Recognition and Management” to be presented on Aug. 12 at HM20 Virtual, the virtual annual meeting of the Society of Hospital Medicine, Megan Kruse, MD, hopes hospitalists will be able to recognize the signs and symptoms of “classic” oncologic emergencies they are likely to see in routine practice, as well as side effects of newer therapies they may not have encountered. Attendees will know how to manage these situations and understand when they need to involve a cancer specialist.
“Early recognition of these emergencies is crucial, and there are simple initial interventions that can make a big difference in patient outcomes,” said Dr. Kruse, an oncologist at the Cleveland Clinic.
In her presentation, Dr. Kruse will review oncologic emergencies that can occur in patients with acute leukemia such as acute blast crisis, as well as spinal cord compression and neutropenic fever. These complications are common in patients with cancer: Many cancers, such as multiple myeloma, lung cancer, and breast cancer, can cause spinal metastases that lead to spinal cord compression, while studies have shown neutropenic fever can occur in up to 80% of patients who undergo chemotherapy.
The presentation also will outline how hospitalists can manage specific side effects of immunotherapy and targeted therapies during an emergency situation. Dr. Kruse noted the session also will focus on when to start steroids for immune-related adverse event concerns and when to think about adding alternate immunosuppression. Complications of these therapies can differ from those of traditional chemotherapy, and not all hospitalists may be expecting them. Side effects from cancer therapy also can present months after treatment, further complicating the nature of oncologic emergencies in a hospital setting.
Recognizing the signs of such emergencies can be crucial for patients, especially if clinical decisions are made before a hospitalist can reach an oncologist for consult. Some decisions can be made by hospitalists themselves, while others may require specialty knowledge from an oncologist, Dr. Kruse noted. Regardless, it is important to consider cancer treatment history in a patient’s differential diagnosis.
Dr. Kruse has given presentations on oncologic emergencies at SHM annual conferences in the past, but notes this year’s virtual presentation will include more cases and examples of complications to improve recognition of these conditions. in patients with oncologic emergencies.
“I hope that attendees will leave with a better idea of what symptoms should be, warning signs of impending oncologic emergencies/complications, and what measures can be taken to treat these conditions prior to oncology service involvement,” Dr. Kruse said.
Dr. Kruse reported advisory board involvement for Novartis Oncology and consulting for Puma Biotechnology.
Getting to Know Oncology Emergencies: Recognition and Management
Live Q&A: Wednesday, Aug. 12, 1:00 p.m. to 2:00 p.m.
During an oncologic emergency, making a clinical decision during the early diagnostic period is one of the most critical things a hospitalist can do when caring for patients with cancer. Hospitalists may not always be well versed in the symptoms of oncologic emergencies, though, particularly with newer treatments like immunotherapy and targeted therapies. They also may be tempted to contact colleagues in oncology when they may be qualified to handle these emergencies on their own.
At the end of her question-and-answer session, “Getting to Know Oncology Emergencies: Recognition and Management” to be presented on Aug. 12 at HM20 Virtual, the virtual annual meeting of the Society of Hospital Medicine, Megan Kruse, MD, hopes hospitalists will be able to recognize the signs and symptoms of “classic” oncologic emergencies they are likely to see in routine practice, as well as side effects of newer therapies they may not have encountered. Attendees will know how to manage these situations and understand when they need to involve a cancer specialist.
“Early recognition of these emergencies is crucial, and there are simple initial interventions that can make a big difference in patient outcomes,” said Dr. Kruse, an oncologist at the Cleveland Clinic.
In her presentation, Dr. Kruse will review oncologic emergencies that can occur in patients with acute leukemia such as acute blast crisis, as well as spinal cord compression and neutropenic fever. These complications are common in patients with cancer: Many cancers, such as multiple myeloma, lung cancer, and breast cancer, can cause spinal metastases that lead to spinal cord compression, while studies have shown neutropenic fever can occur in up to 80% of patients who undergo chemotherapy.
The presentation also will outline how hospitalists can manage specific side effects of immunotherapy and targeted therapies during an emergency situation. Dr. Kruse noted the session also will focus on when to start steroids for immune-related adverse event concerns and when to think about adding alternate immunosuppression. Complications of these therapies can differ from those of traditional chemotherapy, and not all hospitalists may be expecting them. Side effects from cancer therapy also can present months after treatment, further complicating the nature of oncologic emergencies in a hospital setting.
Recognizing the signs of such emergencies can be crucial for patients, especially if clinical decisions are made before a hospitalist can reach an oncologist for consult. Some decisions can be made by hospitalists themselves, while others may require specialty knowledge from an oncologist, Dr. Kruse noted. Regardless, it is important to consider cancer treatment history in a patient’s differential diagnosis.
Dr. Kruse has given presentations on oncologic emergencies at SHM annual conferences in the past, but notes this year’s virtual presentation will include more cases and examples of complications to improve recognition of these conditions. in patients with oncologic emergencies.
“I hope that attendees will leave with a better idea of what symptoms should be, warning signs of impending oncologic emergencies/complications, and what measures can be taken to treat these conditions prior to oncology service involvement,” Dr. Kruse said.
Dr. Kruse reported advisory board involvement for Novartis Oncology and consulting for Puma Biotechnology.
Getting to Know Oncology Emergencies: Recognition and Management
Live Q&A: Wednesday, Aug. 12, 1:00 p.m. to 2:00 p.m.
During an oncologic emergency, making a clinical decision during the early diagnostic period is one of the most critical things a hospitalist can do when caring for patients with cancer. Hospitalists may not always be well versed in the symptoms of oncologic emergencies, though, particularly with newer treatments like immunotherapy and targeted therapies. They also may be tempted to contact colleagues in oncology when they may be qualified to handle these emergencies on their own.
At the end of her question-and-answer session, “Getting to Know Oncology Emergencies: Recognition and Management” to be presented on Aug. 12 at HM20 Virtual, the virtual annual meeting of the Society of Hospital Medicine, Megan Kruse, MD, hopes hospitalists will be able to recognize the signs and symptoms of “classic” oncologic emergencies they are likely to see in routine practice, as well as side effects of newer therapies they may not have encountered. Attendees will know how to manage these situations and understand when they need to involve a cancer specialist.
“Early recognition of these emergencies is crucial, and there are simple initial interventions that can make a big difference in patient outcomes,” said Dr. Kruse, an oncologist at the Cleveland Clinic.
In her presentation, Dr. Kruse will review oncologic emergencies that can occur in patients with acute leukemia such as acute blast crisis, as well as spinal cord compression and neutropenic fever. These complications are common in patients with cancer: Many cancers, such as multiple myeloma, lung cancer, and breast cancer, can cause spinal metastases that lead to spinal cord compression, while studies have shown neutropenic fever can occur in up to 80% of patients who undergo chemotherapy.
The presentation also will outline how hospitalists can manage specific side effects of immunotherapy and targeted therapies during an emergency situation. Dr. Kruse noted the session also will focus on when to start steroids for immune-related adverse event concerns and when to think about adding alternate immunosuppression. Complications of these therapies can differ from those of traditional chemotherapy, and not all hospitalists may be expecting them. Side effects from cancer therapy also can present months after treatment, further complicating the nature of oncologic emergencies in a hospital setting.
Recognizing the signs of such emergencies can be crucial for patients, especially if clinical decisions are made before a hospitalist can reach an oncologist for consult. Some decisions can be made by hospitalists themselves, while others may require specialty knowledge from an oncologist, Dr. Kruse noted. Regardless, it is important to consider cancer treatment history in a patient’s differential diagnosis.
Dr. Kruse has given presentations on oncologic emergencies at SHM annual conferences in the past, but notes this year’s virtual presentation will include more cases and examples of complications to improve recognition of these conditions. in patients with oncologic emergencies.
“I hope that attendees will leave with a better idea of what symptoms should be, warning signs of impending oncologic emergencies/complications, and what measures can be taken to treat these conditions prior to oncology service involvement,” Dr. Kruse said.
Dr. Kruse reported advisory board involvement for Novartis Oncology and consulting for Puma Biotechnology.
Getting to Know Oncology Emergencies: Recognition and Management
Live Q&A: Wednesday, Aug. 12, 1:00 p.m. to 2:00 p.m.
Hospital medicine update highlights research from ‘extended family’
The annual “Update in Hospital Medicine” session will go a step further by highlighting the work and insights of what Dr. Pfeifer affectionately calls the “extended family.”
Scott Kaatz, DO, MSc, SFHM, a hospitalist at Henry Ford Hospital in Detroit, explained that “the Update has a long-standing tradition at the national meeting as an overview of the most impactful or insightful publications relevant to clinicians working in the hospital, which includes internists, pediatricians, obstetricians, family physicians, nurse practitioners, physician assistants, and other specialties.”
Why does the Update embrace such a wide focus? Because there’s a need for a broader perspective, according to Dr. Pfeifer, professor of medicine at the Medical College of Wisconsin, Milwaukee. “The Society of Hospital Medicine Annual Conference has many superb offerings with specific focuses that help attendees fill knowledge and practice gaps and network with individuals with similar interests,” he said. “All of those different offerings highlight something that is very cool about hospital medicine – its diversity. However, it’s also important for us to come together as one big family to support each other and advocate for the larger cause of hospital medicine. With the “Update in Hospital Medicine,” attendees can specifically hear about the clinical changes happening in their “extended family.”
“We will be giving an overview of key new literature across the spectrum of hospital medicine in areas such as sepsis, inclusion/diversity, co-management, and hospital staffing models,” Dr. Kaatz said. “We will also highlight the various different focuses/practices within hospital medicine and the wonderful diversity within the Society of Hospital Medicine. We have coordinated our selection of topics with the Special Interest Groups (SIGs) and the Chapters to make sure we include the voices of our wider membership. This will also allow us to celebrate our diversity by giving shout outs to our SIGs and chapters and showcase the wonderful things going on in hospital medicine, including advances being made by our very own members.”
Dr. Kaatz added that he and Dr. Pfeifer are grateful to the organizers for allowing them to try something new. “Presented papers will reflect the interests of SHM members via a ‘learner needs assessment’ survey,” he said. “Several of the special interest groups and local chapters surveyed their membership and voted on the most impactful papers in the past year. It has been very gratifying to see the level of engagement in our society and to be able to share this important research with a large audience.”
Dr. Pfeifer has no relevant disclosures. Dr. Kaatz discloses research funding to institution (BMS) and consultant/advisory board relationships (BMS, Pfizer and Janssen).
“Update in Hospital Medicine”
The annual “Update in Hospital Medicine” session will go a step further by highlighting the work and insights of what Dr. Pfeifer affectionately calls the “extended family.”
Scott Kaatz, DO, MSc, SFHM, a hospitalist at Henry Ford Hospital in Detroit, explained that “the Update has a long-standing tradition at the national meeting as an overview of the most impactful or insightful publications relevant to clinicians working in the hospital, which includes internists, pediatricians, obstetricians, family physicians, nurse practitioners, physician assistants, and other specialties.”
Why does the Update embrace such a wide focus? Because there’s a need for a broader perspective, according to Dr. Pfeifer, professor of medicine at the Medical College of Wisconsin, Milwaukee. “The Society of Hospital Medicine Annual Conference has many superb offerings with specific focuses that help attendees fill knowledge and practice gaps and network with individuals with similar interests,” he said. “All of those different offerings highlight something that is very cool about hospital medicine – its diversity. However, it’s also important for us to come together as one big family to support each other and advocate for the larger cause of hospital medicine. With the “Update in Hospital Medicine,” attendees can specifically hear about the clinical changes happening in their “extended family.”
“We will be giving an overview of key new literature across the spectrum of hospital medicine in areas such as sepsis, inclusion/diversity, co-management, and hospital staffing models,” Dr. Kaatz said. “We will also highlight the various different focuses/practices within hospital medicine and the wonderful diversity within the Society of Hospital Medicine. We have coordinated our selection of topics with the Special Interest Groups (SIGs) and the Chapters to make sure we include the voices of our wider membership. This will also allow us to celebrate our diversity by giving shout outs to our SIGs and chapters and showcase the wonderful things going on in hospital medicine, including advances being made by our very own members.”
Dr. Kaatz added that he and Dr. Pfeifer are grateful to the organizers for allowing them to try something new. “Presented papers will reflect the interests of SHM members via a ‘learner needs assessment’ survey,” he said. “Several of the special interest groups and local chapters surveyed their membership and voted on the most impactful papers in the past year. It has been very gratifying to see the level of engagement in our society and to be able to share this important research with a large audience.”
Dr. Pfeifer has no relevant disclosures. Dr. Kaatz discloses research funding to institution (BMS) and consultant/advisory board relationships (BMS, Pfizer and Janssen).
“Update in Hospital Medicine”
The annual “Update in Hospital Medicine” session will go a step further by highlighting the work and insights of what Dr. Pfeifer affectionately calls the “extended family.”
Scott Kaatz, DO, MSc, SFHM, a hospitalist at Henry Ford Hospital in Detroit, explained that “the Update has a long-standing tradition at the national meeting as an overview of the most impactful or insightful publications relevant to clinicians working in the hospital, which includes internists, pediatricians, obstetricians, family physicians, nurse practitioners, physician assistants, and other specialties.”
Why does the Update embrace such a wide focus? Because there’s a need for a broader perspective, according to Dr. Pfeifer, professor of medicine at the Medical College of Wisconsin, Milwaukee. “The Society of Hospital Medicine Annual Conference has many superb offerings with specific focuses that help attendees fill knowledge and practice gaps and network with individuals with similar interests,” he said. “All of those different offerings highlight something that is very cool about hospital medicine – its diversity. However, it’s also important for us to come together as one big family to support each other and advocate for the larger cause of hospital medicine. With the “Update in Hospital Medicine,” attendees can specifically hear about the clinical changes happening in their “extended family.”
“We will be giving an overview of key new literature across the spectrum of hospital medicine in areas such as sepsis, inclusion/diversity, co-management, and hospital staffing models,” Dr. Kaatz said. “We will also highlight the various different focuses/practices within hospital medicine and the wonderful diversity within the Society of Hospital Medicine. We have coordinated our selection of topics with the Special Interest Groups (SIGs) and the Chapters to make sure we include the voices of our wider membership. This will also allow us to celebrate our diversity by giving shout outs to our SIGs and chapters and showcase the wonderful things going on in hospital medicine, including advances being made by our very own members.”
Dr. Kaatz added that he and Dr. Pfeifer are grateful to the organizers for allowing them to try something new. “Presented papers will reflect the interests of SHM members via a ‘learner needs assessment’ survey,” he said. “Several of the special interest groups and local chapters surveyed their membership and voted on the most impactful papers in the past year. It has been very gratifying to see the level of engagement in our society and to be able to share this important research with a large audience.”
Dr. Pfeifer has no relevant disclosures. Dr. Kaatz discloses research funding to institution (BMS) and consultant/advisory board relationships (BMS, Pfizer and Janssen).
“Update in Hospital Medicine”
Ex-nursing assistant pleads guilty in West Virginia insulin deaths
A former nursing assistant and Army veteran pleaded guilty to federal murder charges this week in connection with the 2017-2018 deaths of seven patients in a West Virginia veteran’s hospital, according to news reports.
Prosecutors said in court documents filed on July 13 that Reta Mays, 46, injected lethal doses of insulin into seven veterans at the Louis A. Johnson VA Medical Center (VAMC) in rural Clarksburg, W.Va.
Their blood glucose levels plummeted, and each died shortly after their injections, according to the Tennessean.
An eighth patient, a 92-year-old man whom Mays is accused of assaulting with an insulin injection, initially survived after staff were able to stabilize him but died 2 weeks later at a nursing home, NPR reports.
According to NPR, US Attorney Jarod Douglas told the court Tuesday that the medical investigator could not determine whether the insulin contributed to the man’s death but that it was Mays’ intention to kill him.
“No one watched while she injected them with lethal doses of insulin during an 11-month killing rampage,” the Washington Post reported.
No motive offered
The Post article said no motive has been established, but after a 2-year investigation into a pattern of suspicious deaths that took the hospital almost a year to detect, Mays, who had denied any wrongdoing in multiple interviews with investigators, told a federal judge she preyed on some of the country›s most vulnerable service members.
An attorney for Mays, Brian Kornbrath, contacted by Medscape Medical News, said: “The defense team decided that we would have no public comment at this time.”
According to court documents from the Northern District of West Virginia, Mays was charged with seven counts of second-degree murder and one count of assault with intent to commit murder in connection with the patient who died later.
Mays was hired at the VAMC in Clarksburg in June 2015. She worked from 7:30 PM to 8:00 AM in the medical surgical unit, court documents say.
According to the documents, “VAMC Clarksburg did not require a nursing assistant to have a certification or licensure for initial appointment or as a condition of continuing employment.”
The documents indicate that in June 2018, a hospitalist employed by VAMC Clarksburg reported concern about several deaths from unexplained hypoglycemic events in the same ward and noted that many of the affected patients did not have diabetes.
By that time, according to the Tennessean, “at least eight patients had died under suspicious circumstances. Several had been embalmed and buried, destroying potential evidence. One veteran had been cremated.”
An internal investigation began, followed by a criminal investigation, and in July 2018, Mays was removed from patient care.
Mays fired in 2019 because of lies on resume; claims suffers from PTSD
The Post reports that Mays was fired from the hospital in 2019, 7 months after she was banned from patient care, «after it was discovered she had lied about her qualifications on her resume.»
Court documents indicate that her duties included acting as a sitter for patients, checking vital signs, intake and output, and testing blood glucose levels, but she was not qualified to administer medications, including insulin.
Similarities in the deaths were evident, the Post reported. Citing sources familiar with the case, the report said, “elderly patients in private rooms were injected in their abdomen and limbs with insulin the hospital had not ordered.”
The Post reported that Mays sobbed by the end of the hearing on Tuesday.
The article notes that Mays has three sons and served in the Army National Guard from November 2000 to April 2001 and again from February 2003 to May 2004, when she was deployed to Iraq and Kuwait. She told the judge she was taking medication for posttraumatic stress disorder.
By pleading guilty, she waived her right to have the case presented to a grand jury. A sentencing hearing has not been scheduled, the Post reports.
NPR notes that prosecutors have requested that Mays serve seven consecutive life sentences and an additional 20 years in prison.
“Our hearts go out to those affected by these tragic deaths”
A spokesman for VAMC Clarksburg said in a statement to Medscape Medical News: “Our hearts go out to those affected by these tragic deaths. Clarksburg VA Medical Center discovered these allegations and reported them to VA›s independent inspector general more than 2 years ago. Clarksburg VA Medical Center also fired the individual at the center of the allegations.
“We’re glad the Department of Justice stepped in to push this investigation across the finish line and hopeful our court system will deliver the justice Clarksburg-area Veterans and families deserve.”
According to the Tennessean, Michael Missal, inspector general for the Department of Veteran Affairs, said the agency is investigating the hospital’s practices, “including medication management and communications among staffers.”
This article first appeared on Medscape.com.
A former nursing assistant and Army veteran pleaded guilty to federal murder charges this week in connection with the 2017-2018 deaths of seven patients in a West Virginia veteran’s hospital, according to news reports.
Prosecutors said in court documents filed on July 13 that Reta Mays, 46, injected lethal doses of insulin into seven veterans at the Louis A. Johnson VA Medical Center (VAMC) in rural Clarksburg, W.Va.
Their blood glucose levels plummeted, and each died shortly after their injections, according to the Tennessean.
An eighth patient, a 92-year-old man whom Mays is accused of assaulting with an insulin injection, initially survived after staff were able to stabilize him but died 2 weeks later at a nursing home, NPR reports.
According to NPR, US Attorney Jarod Douglas told the court Tuesday that the medical investigator could not determine whether the insulin contributed to the man’s death but that it was Mays’ intention to kill him.
“No one watched while she injected them with lethal doses of insulin during an 11-month killing rampage,” the Washington Post reported.
No motive offered
The Post article said no motive has been established, but after a 2-year investigation into a pattern of suspicious deaths that took the hospital almost a year to detect, Mays, who had denied any wrongdoing in multiple interviews with investigators, told a federal judge she preyed on some of the country›s most vulnerable service members.
An attorney for Mays, Brian Kornbrath, contacted by Medscape Medical News, said: “The defense team decided that we would have no public comment at this time.”
According to court documents from the Northern District of West Virginia, Mays was charged with seven counts of second-degree murder and one count of assault with intent to commit murder in connection with the patient who died later.
Mays was hired at the VAMC in Clarksburg in June 2015. She worked from 7:30 PM to 8:00 AM in the medical surgical unit, court documents say.
According to the documents, “VAMC Clarksburg did not require a nursing assistant to have a certification or licensure for initial appointment or as a condition of continuing employment.”
The documents indicate that in June 2018, a hospitalist employed by VAMC Clarksburg reported concern about several deaths from unexplained hypoglycemic events in the same ward and noted that many of the affected patients did not have diabetes.
By that time, according to the Tennessean, “at least eight patients had died under suspicious circumstances. Several had been embalmed and buried, destroying potential evidence. One veteran had been cremated.”
An internal investigation began, followed by a criminal investigation, and in July 2018, Mays was removed from patient care.
Mays fired in 2019 because of lies on resume; claims suffers from PTSD
The Post reports that Mays was fired from the hospital in 2019, 7 months after she was banned from patient care, «after it was discovered she had lied about her qualifications on her resume.»
Court documents indicate that her duties included acting as a sitter for patients, checking vital signs, intake and output, and testing blood glucose levels, but she was not qualified to administer medications, including insulin.
Similarities in the deaths were evident, the Post reported. Citing sources familiar with the case, the report said, “elderly patients in private rooms were injected in their abdomen and limbs with insulin the hospital had not ordered.”
The Post reported that Mays sobbed by the end of the hearing on Tuesday.
The article notes that Mays has three sons and served in the Army National Guard from November 2000 to April 2001 and again from February 2003 to May 2004, when she was deployed to Iraq and Kuwait. She told the judge she was taking medication for posttraumatic stress disorder.
By pleading guilty, she waived her right to have the case presented to a grand jury. A sentencing hearing has not been scheduled, the Post reports.
NPR notes that prosecutors have requested that Mays serve seven consecutive life sentences and an additional 20 years in prison.
“Our hearts go out to those affected by these tragic deaths”
A spokesman for VAMC Clarksburg said in a statement to Medscape Medical News: “Our hearts go out to those affected by these tragic deaths. Clarksburg VA Medical Center discovered these allegations and reported them to VA›s independent inspector general more than 2 years ago. Clarksburg VA Medical Center also fired the individual at the center of the allegations.
“We’re glad the Department of Justice stepped in to push this investigation across the finish line and hopeful our court system will deliver the justice Clarksburg-area Veterans and families deserve.”
According to the Tennessean, Michael Missal, inspector general for the Department of Veteran Affairs, said the agency is investigating the hospital’s practices, “including medication management and communications among staffers.”
This article first appeared on Medscape.com.
A former nursing assistant and Army veteran pleaded guilty to federal murder charges this week in connection with the 2017-2018 deaths of seven patients in a West Virginia veteran’s hospital, according to news reports.
Prosecutors said in court documents filed on July 13 that Reta Mays, 46, injected lethal doses of insulin into seven veterans at the Louis A. Johnson VA Medical Center (VAMC) in rural Clarksburg, W.Va.
Their blood glucose levels plummeted, and each died shortly after their injections, according to the Tennessean.
An eighth patient, a 92-year-old man whom Mays is accused of assaulting with an insulin injection, initially survived after staff were able to stabilize him but died 2 weeks later at a nursing home, NPR reports.
According to NPR, US Attorney Jarod Douglas told the court Tuesday that the medical investigator could not determine whether the insulin contributed to the man’s death but that it was Mays’ intention to kill him.
“No one watched while she injected them with lethal doses of insulin during an 11-month killing rampage,” the Washington Post reported.
No motive offered
The Post article said no motive has been established, but after a 2-year investigation into a pattern of suspicious deaths that took the hospital almost a year to detect, Mays, who had denied any wrongdoing in multiple interviews with investigators, told a federal judge she preyed on some of the country›s most vulnerable service members.
An attorney for Mays, Brian Kornbrath, contacted by Medscape Medical News, said: “The defense team decided that we would have no public comment at this time.”
According to court documents from the Northern District of West Virginia, Mays was charged with seven counts of second-degree murder and one count of assault with intent to commit murder in connection with the patient who died later.
Mays was hired at the VAMC in Clarksburg in June 2015. She worked from 7:30 PM to 8:00 AM in the medical surgical unit, court documents say.
According to the documents, “VAMC Clarksburg did not require a nursing assistant to have a certification or licensure for initial appointment or as a condition of continuing employment.”
The documents indicate that in June 2018, a hospitalist employed by VAMC Clarksburg reported concern about several deaths from unexplained hypoglycemic events in the same ward and noted that many of the affected patients did not have diabetes.
By that time, according to the Tennessean, “at least eight patients had died under suspicious circumstances. Several had been embalmed and buried, destroying potential evidence. One veteran had been cremated.”
An internal investigation began, followed by a criminal investigation, and in July 2018, Mays was removed from patient care.
Mays fired in 2019 because of lies on resume; claims suffers from PTSD
The Post reports that Mays was fired from the hospital in 2019, 7 months after she was banned from patient care, «after it was discovered she had lied about her qualifications on her resume.»
Court documents indicate that her duties included acting as a sitter for patients, checking vital signs, intake and output, and testing blood glucose levels, but she was not qualified to administer medications, including insulin.
Similarities in the deaths were evident, the Post reported. Citing sources familiar with the case, the report said, “elderly patients in private rooms were injected in their abdomen and limbs with insulin the hospital had not ordered.”
The Post reported that Mays sobbed by the end of the hearing on Tuesday.
The article notes that Mays has three sons and served in the Army National Guard from November 2000 to April 2001 and again from February 2003 to May 2004, when she was deployed to Iraq and Kuwait. She told the judge she was taking medication for posttraumatic stress disorder.
By pleading guilty, she waived her right to have the case presented to a grand jury. A sentencing hearing has not been scheduled, the Post reports.
NPR notes that prosecutors have requested that Mays serve seven consecutive life sentences and an additional 20 years in prison.
“Our hearts go out to those affected by these tragic deaths”
A spokesman for VAMC Clarksburg said in a statement to Medscape Medical News: “Our hearts go out to those affected by these tragic deaths. Clarksburg VA Medical Center discovered these allegations and reported them to VA›s independent inspector general more than 2 years ago. Clarksburg VA Medical Center also fired the individual at the center of the allegations.
“We’re glad the Department of Justice stepped in to push this investigation across the finish line and hopeful our court system will deliver the justice Clarksburg-area Veterans and families deserve.”
According to the Tennessean, Michael Missal, inspector general for the Department of Veteran Affairs, said the agency is investigating the hospital’s practices, “including medication management and communications among staffers.”
This article first appeared on Medscape.com.
August 2020 – ICYMI
Gastroenterology
May 2020
Mechanisms of fibrosis development in nonalcoholic steatohepatitis. Robert F. Schwabe et al. 2020 May;158(7):1913-28. doi: 10.1053/j.gastro.2019.11.311
June 2020
Cognitive deficit and white matter changes in persons with celiac disease: A population-based study. Iain D. Croall et al. 2020 Jun;158(8):2112-22. doi: 10.1053/j.gastro.2020.02.028
Efficacy and safety of upadacitinib in a randomized trial of patients with Crohn’s disease. William J. Sandborn et al. 2020 Jun;158(8):2123-38.e8. doi: 10.1053/j.gastro.2020.01.047
The path to gastroenterology leadership: The preparation, the process, and achieving success. Joseph Ahn et al. 2020 Jun;158(8):2033-6.e4. doi: 10.1053/j.gastro.2020.01.054
Clinical Gastroenterology and Hepatology
May 2020
A user’s guide to de-escalating immunomodulator and biologic therapy in inflammatory bowel disease. Robert P. Hirten et al. 2020 May;18(6);1336-45. doi: 10.1016/j.cgh.2019.12.019
Dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases. Arie Levine et al. 2020 May;18(6):1381-92. doi: 10.1016/j.cgh.2020.01.046
Management of patients with immune checkpoint inhibitor-induced enterocolitis: A systematic review. Michael Collins et al. 2020 May;18(6):1393-403.e1. doi: 10.1016/j.cgh.2020.01.033
June 2020
Worldwide variations in demographics, management, and outcomes of acute pancreatitis. Bassem Matta et al. 2020 Jun;18(7):1567-75.e2. doi: 10.1016/j.cgh.2019.11.017
Rapid recurrence of eosinophilic esophagitis activity after successful treatment in the observation phase of a randomized, double-blind, double-dummy trial. Evan S. Dellon et al. 2020 Jun;18(7):1483-92.e2. doi: 10.1016/j.cgh.2019.08.050
July 2020
Disparities in colorectal cancer screening in the United States before and after implementation of the Affordable Care Act. Folasade P. May et al. 2020 Jul;18(8):1796-804.e2. doi: 10.1016/j.cgh.2019.09.008
Cost-effectiveness of telemedicine-directed specialized vs. standard care for patients with inflammatory bowel diseases in a randomized trial. Marin J. de Jong et al. 2020 Jul;18(8):1744-52. doi: 10.1016/j.cgh.2020.04.038
Artificial intelligence-assisted system improves endoscopic identification of colorectal neoplasms. Shin-ei Kudo et al. 2020 Jul;18(8):1874-81.e2. doi: 10.1016/j.cgh.2019.09.009
Gastroenterology
May 2020
Mechanisms of fibrosis development in nonalcoholic steatohepatitis. Robert F. Schwabe et al. 2020 May;158(7):1913-28. doi: 10.1053/j.gastro.2019.11.311
June 2020
Cognitive deficit and white matter changes in persons with celiac disease: A population-based study. Iain D. Croall et al. 2020 Jun;158(8):2112-22. doi: 10.1053/j.gastro.2020.02.028
Efficacy and safety of upadacitinib in a randomized trial of patients with Crohn’s disease. William J. Sandborn et al. 2020 Jun;158(8):2123-38.e8. doi: 10.1053/j.gastro.2020.01.047
The path to gastroenterology leadership: The preparation, the process, and achieving success. Joseph Ahn et al. 2020 Jun;158(8):2033-6.e4. doi: 10.1053/j.gastro.2020.01.054
Clinical Gastroenterology and Hepatology
May 2020
A user’s guide to de-escalating immunomodulator and biologic therapy in inflammatory bowel disease. Robert P. Hirten et al. 2020 May;18(6);1336-45. doi: 10.1016/j.cgh.2019.12.019
Dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases. Arie Levine et al. 2020 May;18(6):1381-92. doi: 10.1016/j.cgh.2020.01.046
Management of patients with immune checkpoint inhibitor-induced enterocolitis: A systematic review. Michael Collins et al. 2020 May;18(6):1393-403.e1. doi: 10.1016/j.cgh.2020.01.033
June 2020
Worldwide variations in demographics, management, and outcomes of acute pancreatitis. Bassem Matta et al. 2020 Jun;18(7):1567-75.e2. doi: 10.1016/j.cgh.2019.11.017
Rapid recurrence of eosinophilic esophagitis activity after successful treatment in the observation phase of a randomized, double-blind, double-dummy trial. Evan S. Dellon et al. 2020 Jun;18(7):1483-92.e2. doi: 10.1016/j.cgh.2019.08.050
July 2020
Disparities in colorectal cancer screening in the United States before and after implementation of the Affordable Care Act. Folasade P. May et al. 2020 Jul;18(8):1796-804.e2. doi: 10.1016/j.cgh.2019.09.008
Cost-effectiveness of telemedicine-directed specialized vs. standard care for patients with inflammatory bowel diseases in a randomized trial. Marin J. de Jong et al. 2020 Jul;18(8):1744-52. doi: 10.1016/j.cgh.2020.04.038
Artificial intelligence-assisted system improves endoscopic identification of colorectal neoplasms. Shin-ei Kudo et al. 2020 Jul;18(8):1874-81.e2. doi: 10.1016/j.cgh.2019.09.009
Gastroenterology
May 2020
Mechanisms of fibrosis development in nonalcoholic steatohepatitis. Robert F. Schwabe et al. 2020 May;158(7):1913-28. doi: 10.1053/j.gastro.2019.11.311
June 2020
Cognitive deficit and white matter changes in persons with celiac disease: A population-based study. Iain D. Croall et al. 2020 Jun;158(8):2112-22. doi: 10.1053/j.gastro.2020.02.028
Efficacy and safety of upadacitinib in a randomized trial of patients with Crohn’s disease. William J. Sandborn et al. 2020 Jun;158(8):2123-38.e8. doi: 10.1053/j.gastro.2020.01.047
The path to gastroenterology leadership: The preparation, the process, and achieving success. Joseph Ahn et al. 2020 Jun;158(8):2033-6.e4. doi: 10.1053/j.gastro.2020.01.054
Clinical Gastroenterology and Hepatology
May 2020
A user’s guide to de-escalating immunomodulator and biologic therapy in inflammatory bowel disease. Robert P. Hirten et al. 2020 May;18(6);1336-45. doi: 10.1016/j.cgh.2019.12.019
Dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases. Arie Levine et al. 2020 May;18(6):1381-92. doi: 10.1016/j.cgh.2020.01.046
Management of patients with immune checkpoint inhibitor-induced enterocolitis: A systematic review. Michael Collins et al. 2020 May;18(6):1393-403.e1. doi: 10.1016/j.cgh.2020.01.033
June 2020
Worldwide variations in demographics, management, and outcomes of acute pancreatitis. Bassem Matta et al. 2020 Jun;18(7):1567-75.e2. doi: 10.1016/j.cgh.2019.11.017
Rapid recurrence of eosinophilic esophagitis activity after successful treatment in the observation phase of a randomized, double-blind, double-dummy trial. Evan S. Dellon et al. 2020 Jun;18(7):1483-92.e2. doi: 10.1016/j.cgh.2019.08.050
July 2020
Disparities in colorectal cancer screening in the United States before and after implementation of the Affordable Care Act. Folasade P. May et al. 2020 Jul;18(8):1796-804.e2. doi: 10.1016/j.cgh.2019.09.008
Cost-effectiveness of telemedicine-directed specialized vs. standard care for patients with inflammatory bowel diseases in a randomized trial. Marin J. de Jong et al. 2020 Jul;18(8):1744-52. doi: 10.1016/j.cgh.2020.04.038
Artificial intelligence-assisted system improves endoscopic identification of colorectal neoplasms. Shin-ei Kudo et al. 2020 Jul;18(8):1874-81.e2. doi: 10.1016/j.cgh.2019.09.009
Exposing hospital gowns
Bare bottoms, bare minimum
“Don’t let the gown get you down,” was the advice a 26-year-old gentleman with leukemia offered in a study investigating the psychosocial impact of hospital gowns on patients and providers.1 Patients were found to be resigned to their “uncomfortable,” “expos[ing],” “nightmare-[ish]” “uniform,” afraid to even ask to wear more dignifying attire for fear of seeming difficult to providers and potentially harming the therapeutic relationship; one 64-year-old woman with terminal cancer detailed, “I have my own pajamas at home, but I don’t bring them because you can’t wear them here … [wearing a gown] is really not fun, but hey, this is what [providers] have to do, so it’s what you have to do.”1-3
Research has consistently shown that patients are vulnerable to dehumanization and loss of identity in the hospital, often exacerbated by wearing the standard hospital gown.3-8 Case in point, a mixed-methods study revealed that hospital gowns may lead to an increased sense of exposure, discomfort, disempowerment, and embarrassment for patients during a period of potential vulnerability while undergoing medical intervention.8
Hospital gowns strip autonomy from individuals humbly coming to the hospital for help. The gown has become a linchpin of change, initiating the dehumanizing process of “person” to “patient.” One of the main problems with the hospital gown is its exposing nature, often made light of on the wards with the joke, “Do you know who invented the hospital gown?…See-more Hiney!” The joke continued in two Super Bowl LIII commercials for a large academic health care system and insurance provider in Pennsylvania, depicting a construction worker and businessman clad in hospital gowns, mooning their less-than-pleased coworkers, to inform patients of expanded insurance coverage, i.e., “completely covered.” Hospital gowns are also a source of comedic fodder on sitcoms, including “It’s Always Sunny in Philadelphia,” “Man with a Plan,” and “Carol’s Second Act.”
It is common knowledge that hospital gowns are flawed, but very little has been done to change them. Little is known about the origin of hospital gowns, and like their design, their history has many gaps. PubMed, Google, and Wikipedia yield no fruitful insight into the evolution of the hospital gown, and perhaps the best way to understand the hospital gown over time is to watch depictions of patients in television sitcoms, dramas, and movies, ranging from the days of black-and-white into the modern era, and view artistic depictions of hospitals across eras. Case in point, depictions of fourteenth century hospital wards in art show that all patients wore night shirts, under which they also wore some type of underclothing.9 By the end of the 1800s and beginning of the 1900s, pajamas for men became more common as hospital attire.9 Although it is not known who originally invented the traditional hospital gown, the original gown was designed around a century ago with an open back for use on patients admitted the night prior to surgery, who were sedated prior to transfer to the anesthetic room while half-asleep.10
In general, the most common reason that hospitals began to provide, require, or offer clothing to patients was to reduce infection and improve hygiene, as clothing can be ruined by leakage of bodily fluids from various examinations, treatments, and procedures.9 In addition, in certain settings, lifesaving measures require access to the naked body to allow equipment, like a defibrillator, to be connected to the patient; a gown can theoretically be removed quickly.9 For some reason along the way, the simple, open-backed “johnny” gown of the early 20th century became standard of care with minimal meaningful modifications in the last hundred years. One possible explanation for the persistence of the “johnny” gown is that in past eras of medicine, patients in gowns were expected to be bedbound for recovery, keeping their bare bottom under wraps, and this norm became the status quo. Today, ambulation is encouraged in patients as part of venous thromboembolism (VTE) prophylaxis but the gown design has fallen behind.
Modern medicine emphasizes, values, and even advertises evidence-based medicine, patient-centered care, and high-quality care, yet the hospital gown stands as a stark contrast to this pledge to move forward as beacons of change. Hospital gowns have fallen outside of the scope of evidence-based research.11 One may ask why the gown remains decades behind modern medicine, and it appears that this apathy stems from (1) accepting “medical tradition” and choosing to overlook the flaws of the current hospital gown, and (2) believing that changing the hospital gown would cost money, affronting an institution’s almighty bottom-line. Still, several institutions have attempted change, including Hackensack University Medical Center partnering with Cynthia Rowley and Nicole Miller (1999), Cleveland Clinic partnering with Diane von Furstenberg (2010), and Henry Ford Health System of Detroit’s “Model G” gown (2016).12-15
In spite of these efforts to revamp the hospital gown at academic medical centers, change has been neither long lasting nor widely disseminated. Traci Lamar, a professor at the North Carolina State University College of Textiles reasoned that, “There are number of pressures in the hospital environment that influence what they purchase and when they purchase. Cost management, inventory management, storage space. ... There’s more value coming with the apparel item if it also becomes something that replaces or enhances other equipment that’s used in the hospital environment. Like a gown that can also keep an eye on your blood pressure or measure your heart rate.”15
The hospital gown remains a poor attempt at proper attire for human beings, with the most similar evolutionary relative being a hairdresser’s cape. Taken a step further, functionally the hospital gown is most similar to a prison uniform. Although this may seem bold and sensational, one must stop and think about it, considering the parallels. When individuals are admitted to the hospital, they exchange their clothing for a hospital gown, so that they can be easily identified as a “patient” and remain safe in the hospital. When individuals are sentenced to prison, they exchange their clothing for a uniform, so that they can be easily identified as a “prisoner” and remain safe in jail. The problem is, more time, money, and effort has gone into designing prisoners’ garments, who expect a loss of autonomy, than designing patients’ garments, who should never expect a loss of autonomy.
Prison uniforms are designed with safety in mind, ensuring the absence of potential ligatures or improvised weapons. The United Nations even passed an amendment to its Standard Minimum Rules for the Treatment of Prisoners in 2015, prohibiting humiliating clothing and requiring every prisoner who is “not allowed to wear his or her own clothing” to “be provided with an outfit of clothing suitable for the climate and adequate to keep him or her in good health.”16 They also stipulated that prisoners’ clothing could not be degrading or humiliating and was mandated to “be clean and kept in proper condition”.16 Even more compelling, a physician was bequeathed the task of inspecting, and advising the prison director on “the suitability and cleanliness of the prisoners’ clothing and bedding.”16 However, there are no standard minimum rules for hospital patients’ clothing. Hospital gowns have been described as “threadbare,” “one-size-fits-none,” “stained,” and “drafty,” antithetical to both hygiene and the hospital climate – far from “proper condition” (See Figure 1).1
Where are the standard minimum rules for hospital gowns? Patients have admittedly wondered, “What happened to the person who wore this gown before I did?” or worse, “Who died in this gown?” Even more, the current hospital gown can unintentionally put a patient in harms’ way, posing a fall risk for patients with petite frames overwhelmed by the bulk of the gown and also inhibiting fast access to the chest for placement of defibrillation pads in a code. Ironically, prison uniforms have the main things patients have requested: bottoms, modesty, multiple sizes, and … color!1-3
Although jailhouse orange or stripes are unlikely to be high fashion in the hospital, it is important to consider that, through indifference about the current hospital gown, institutions are teaching that it is acceptable for patients to wear this dehumanizing garment analogous to a prison uniform, except less colorful and more exposing. The hospital gown has persisted under the myth of medical tradition, masking the fact that there is neither evidence for the current hospital gown design nor data to support its functional success for patients or providers.3,12,14 Silence speaks volumes, and patients are taught to expect and accept a loss of dignity without questioning this archaic aspect of medical culture. Patients, nurses, and physicians do not challenge the status quo because the hospital gown “is the way it has always been done.” Perceived added-cost and medical tradition have further perpetuated the current open-backed hospital gown because meaningful change would require money.
With that said, “double gowning,” the method hospitals have used to combat lunar eclipses in the hallways and provide a semblance of dignity to patients, is already costing hospitals more money, costs that can be reduced by creating an evidence-based, patient-guided, provider-approved design. As Mike Forbes, the product designer and licensing associate for the Model G gown, argued, “By using two, you’re purchasing two gowns because one doesn’t do the job, which costs money. … If you’re washing twice as many gowns as you need, you’re spending twice as much money as you need on laundry.”17
Thus, improvements can be made without breaking the bank and may even save hospitals money in the long run. For instance, a hospital administrator can order more colors or styles of hospital gowns and bottoms to give patients a choice of what they would prefer to wear: a small piece of autonomy in an environment where minimal autonomy exists. A physician or nurse can not only permit, but also encourage, a patient to wear his or her own attire within reason, for example, a loose-fitting t-shirt and sweatpants from home or pajama pants under a hospital gown. More complex solutions could include a community design contest for a medical center’s new hospital gown print, or even bolder, a community design contest for a medical center’s new inpatient attire. Above all, patients need to know that hospitals and providers care about what patients wear in the hospital. As a terminally ill patient suggested, “maybe all administrators and office staff should have to spend one day in a gown. …They advertise this: ‘We always put the patient first.’ Okay, so then I guess you have to put your money where your mouth is.”3
This new decade offers the opportunity to give patients a sense of dignity back and make concerted, evidence-based efforts towards meaningful and sustainable change in patient attire, be it purchasing more colorful and modest gown options in the present or total redesign in the future. The financial cost may seem burdensome, but the reward would be immensely bountiful. It is time to stop making hospital gown–clad patients’ exposed bottoms the butt of the joke, and the only way to change the punchline is to change the hospital gown. Patients deserve more than the bare minimum and a bare bottom, so hospitals must consider putting their money where their mouth is.
Dr. Lucas is based in the department of pediatrics, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh. She has a provisional utility patent pending for a novel patient gown. You can contact her at [email protected]. Dr. Dellasega is based in the department of humanities, Penn State University, Hershey.
References
1. Lucas C et al. “Don’t let the gown get you down: How patients and providers perceive hospital gowns.” Abstract published at Hospital Medicine 2019, Mar 24-27, National Harbor, Md., Abstract 322.
2. Lucas C and Dellasega C. “You don’t have to be dying to do comfort measures: Patients’ and physicians’ perceptions of inpatient attire.” Abstract published at ACP Internal Medicine 2019, Apr 11-13, Philadelphia, Abstract.
3. Lucas C and Dellasega C. Finding common threads: How patients, physicians, and nurses perceive the patient gown. Patient Exp J. 2020;7(1):51-64.
4. Detsky A and Krumholtz H. Reducing the trauma of hospitalization. JAMA. 2014;311(21):2169-70.
5. Krumholz H. Post-hospital syndrome – an acquired, transient condition of generalized risk. N Engl J Med. 2013;368(2):100-2.
6. Wellbery C and Chan M. White coat, patient gown. Med Humanit. 2014;40(2):90-6.
7. McDonald E et al. Inpatient attire: An opportunity to improve the patient experience. JAMA Intern Med. 2014;174(11):1865-67.
8. Cogan N et al. Mixed methods study exploring the impact of the hospital gown on recovery and wellbeing: Implications for policy and practice. Lancet. 2019. doi: 10.1016/S0140-6736(19)32829-6.
9. Bergbom I, Pettersson M, and Mattsson E. Patient clothing – practical solution or means of imposing anonymity? J Hosp Med Manage. 2017;3(22):1-6.
10. Who invented the hospital gown? Interweave Healthcare. Accessed Mar 30, 2020.
11. Gordon L and Guttmann S. A user-centered approach to the redesign of the patient hospital gown. Fashion Practice. 2013;5(1):137-51. doi: 10.2752/175693813X13559997788961.
12. Limbong A. “Can a Patient Gown Makeover Move Hospitals to Embrace Change?” NPR. 2018 Feb 11. Accessed Mar 26, 2020.
13. Schiro A. “Patterns: Hospital Style.” New York Times. 1999 June 29. Accessed Mar 26, 2020.
14. Luthra S. “Hospital Gowns Get a Makeover.” The Atlantic. 2015 Apr 4. Accessed Mar 26, 2020.
15. Tien E. “Hospital Gowns Get a Life.” New York Times. 1998 Oct 18. Accessed Mar 26, 2020.
16. McCall-Smith K. United Nations Standard Minimum Rules for the Treatment of Prisoners (Nelson Mandela Rules). Int Leg Materials. 2016;55(6),1180-205.
17. Green C. “Updated hospital gowns a good investment, execs say, restore ‘dignity.’ ” Healthcare Finance. 2015 Aug 3. Accessed Apr 1, 2020.
Bare bottoms, bare minimum
Bare bottoms, bare minimum
“Don’t let the gown get you down,” was the advice a 26-year-old gentleman with leukemia offered in a study investigating the psychosocial impact of hospital gowns on patients and providers.1 Patients were found to be resigned to their “uncomfortable,” “expos[ing],” “nightmare-[ish]” “uniform,” afraid to even ask to wear more dignifying attire for fear of seeming difficult to providers and potentially harming the therapeutic relationship; one 64-year-old woman with terminal cancer detailed, “I have my own pajamas at home, but I don’t bring them because you can’t wear them here … [wearing a gown] is really not fun, but hey, this is what [providers] have to do, so it’s what you have to do.”1-3
Research has consistently shown that patients are vulnerable to dehumanization and loss of identity in the hospital, often exacerbated by wearing the standard hospital gown.3-8 Case in point, a mixed-methods study revealed that hospital gowns may lead to an increased sense of exposure, discomfort, disempowerment, and embarrassment for patients during a period of potential vulnerability while undergoing medical intervention.8
Hospital gowns strip autonomy from individuals humbly coming to the hospital for help. The gown has become a linchpin of change, initiating the dehumanizing process of “person” to “patient.” One of the main problems with the hospital gown is its exposing nature, often made light of on the wards with the joke, “Do you know who invented the hospital gown?…See-more Hiney!” The joke continued in two Super Bowl LIII commercials for a large academic health care system and insurance provider in Pennsylvania, depicting a construction worker and businessman clad in hospital gowns, mooning their less-than-pleased coworkers, to inform patients of expanded insurance coverage, i.e., “completely covered.” Hospital gowns are also a source of comedic fodder on sitcoms, including “It’s Always Sunny in Philadelphia,” “Man with a Plan,” and “Carol’s Second Act.”
It is common knowledge that hospital gowns are flawed, but very little has been done to change them. Little is known about the origin of hospital gowns, and like their design, their history has many gaps. PubMed, Google, and Wikipedia yield no fruitful insight into the evolution of the hospital gown, and perhaps the best way to understand the hospital gown over time is to watch depictions of patients in television sitcoms, dramas, and movies, ranging from the days of black-and-white into the modern era, and view artistic depictions of hospitals across eras. Case in point, depictions of fourteenth century hospital wards in art show that all patients wore night shirts, under which they also wore some type of underclothing.9 By the end of the 1800s and beginning of the 1900s, pajamas for men became more common as hospital attire.9 Although it is not known who originally invented the traditional hospital gown, the original gown was designed around a century ago with an open back for use on patients admitted the night prior to surgery, who were sedated prior to transfer to the anesthetic room while half-asleep.10
In general, the most common reason that hospitals began to provide, require, or offer clothing to patients was to reduce infection and improve hygiene, as clothing can be ruined by leakage of bodily fluids from various examinations, treatments, and procedures.9 In addition, in certain settings, lifesaving measures require access to the naked body to allow equipment, like a defibrillator, to be connected to the patient; a gown can theoretically be removed quickly.9 For some reason along the way, the simple, open-backed “johnny” gown of the early 20th century became standard of care with minimal meaningful modifications in the last hundred years. One possible explanation for the persistence of the “johnny” gown is that in past eras of medicine, patients in gowns were expected to be bedbound for recovery, keeping their bare bottom under wraps, and this norm became the status quo. Today, ambulation is encouraged in patients as part of venous thromboembolism (VTE) prophylaxis but the gown design has fallen behind.
Modern medicine emphasizes, values, and even advertises evidence-based medicine, patient-centered care, and high-quality care, yet the hospital gown stands as a stark contrast to this pledge to move forward as beacons of change. Hospital gowns have fallen outside of the scope of evidence-based research.11 One may ask why the gown remains decades behind modern medicine, and it appears that this apathy stems from (1) accepting “medical tradition” and choosing to overlook the flaws of the current hospital gown, and (2) believing that changing the hospital gown would cost money, affronting an institution’s almighty bottom-line. Still, several institutions have attempted change, including Hackensack University Medical Center partnering with Cynthia Rowley and Nicole Miller (1999), Cleveland Clinic partnering with Diane von Furstenberg (2010), and Henry Ford Health System of Detroit’s “Model G” gown (2016).12-15
In spite of these efforts to revamp the hospital gown at academic medical centers, change has been neither long lasting nor widely disseminated. Traci Lamar, a professor at the North Carolina State University College of Textiles reasoned that, “There are number of pressures in the hospital environment that influence what they purchase and when they purchase. Cost management, inventory management, storage space. ... There’s more value coming with the apparel item if it also becomes something that replaces or enhances other equipment that’s used in the hospital environment. Like a gown that can also keep an eye on your blood pressure or measure your heart rate.”15
The hospital gown remains a poor attempt at proper attire for human beings, with the most similar evolutionary relative being a hairdresser’s cape. Taken a step further, functionally the hospital gown is most similar to a prison uniform. Although this may seem bold and sensational, one must stop and think about it, considering the parallels. When individuals are admitted to the hospital, they exchange their clothing for a hospital gown, so that they can be easily identified as a “patient” and remain safe in the hospital. When individuals are sentenced to prison, they exchange their clothing for a uniform, so that they can be easily identified as a “prisoner” and remain safe in jail. The problem is, more time, money, and effort has gone into designing prisoners’ garments, who expect a loss of autonomy, than designing patients’ garments, who should never expect a loss of autonomy.
Prison uniforms are designed with safety in mind, ensuring the absence of potential ligatures or improvised weapons. The United Nations even passed an amendment to its Standard Minimum Rules for the Treatment of Prisoners in 2015, prohibiting humiliating clothing and requiring every prisoner who is “not allowed to wear his or her own clothing” to “be provided with an outfit of clothing suitable for the climate and adequate to keep him or her in good health.”16 They also stipulated that prisoners’ clothing could not be degrading or humiliating and was mandated to “be clean and kept in proper condition”.16 Even more compelling, a physician was bequeathed the task of inspecting, and advising the prison director on “the suitability and cleanliness of the prisoners’ clothing and bedding.”16 However, there are no standard minimum rules for hospital patients’ clothing. Hospital gowns have been described as “threadbare,” “one-size-fits-none,” “stained,” and “drafty,” antithetical to both hygiene and the hospital climate – far from “proper condition” (See Figure 1).1
Where are the standard minimum rules for hospital gowns? Patients have admittedly wondered, “What happened to the person who wore this gown before I did?” or worse, “Who died in this gown?” Even more, the current hospital gown can unintentionally put a patient in harms’ way, posing a fall risk for patients with petite frames overwhelmed by the bulk of the gown and also inhibiting fast access to the chest for placement of defibrillation pads in a code. Ironically, prison uniforms have the main things patients have requested: bottoms, modesty, multiple sizes, and … color!1-3
Although jailhouse orange or stripes are unlikely to be high fashion in the hospital, it is important to consider that, through indifference about the current hospital gown, institutions are teaching that it is acceptable for patients to wear this dehumanizing garment analogous to a prison uniform, except less colorful and more exposing. The hospital gown has persisted under the myth of medical tradition, masking the fact that there is neither evidence for the current hospital gown design nor data to support its functional success for patients or providers.3,12,14 Silence speaks volumes, and patients are taught to expect and accept a loss of dignity without questioning this archaic aspect of medical culture. Patients, nurses, and physicians do not challenge the status quo because the hospital gown “is the way it has always been done.” Perceived added-cost and medical tradition have further perpetuated the current open-backed hospital gown because meaningful change would require money.
With that said, “double gowning,” the method hospitals have used to combat lunar eclipses in the hallways and provide a semblance of dignity to patients, is already costing hospitals more money, costs that can be reduced by creating an evidence-based, patient-guided, provider-approved design. As Mike Forbes, the product designer and licensing associate for the Model G gown, argued, “By using two, you’re purchasing two gowns because one doesn’t do the job, which costs money. … If you’re washing twice as many gowns as you need, you’re spending twice as much money as you need on laundry.”17
Thus, improvements can be made without breaking the bank and may even save hospitals money in the long run. For instance, a hospital administrator can order more colors or styles of hospital gowns and bottoms to give patients a choice of what they would prefer to wear: a small piece of autonomy in an environment where minimal autonomy exists. A physician or nurse can not only permit, but also encourage, a patient to wear his or her own attire within reason, for example, a loose-fitting t-shirt and sweatpants from home or pajama pants under a hospital gown. More complex solutions could include a community design contest for a medical center’s new hospital gown print, or even bolder, a community design contest for a medical center’s new inpatient attire. Above all, patients need to know that hospitals and providers care about what patients wear in the hospital. As a terminally ill patient suggested, “maybe all administrators and office staff should have to spend one day in a gown. …They advertise this: ‘We always put the patient first.’ Okay, so then I guess you have to put your money where your mouth is.”3
This new decade offers the opportunity to give patients a sense of dignity back and make concerted, evidence-based efforts towards meaningful and sustainable change in patient attire, be it purchasing more colorful and modest gown options in the present or total redesign in the future. The financial cost may seem burdensome, but the reward would be immensely bountiful. It is time to stop making hospital gown–clad patients’ exposed bottoms the butt of the joke, and the only way to change the punchline is to change the hospital gown. Patients deserve more than the bare minimum and a bare bottom, so hospitals must consider putting their money where their mouth is.
Dr. Lucas is based in the department of pediatrics, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh. She has a provisional utility patent pending for a novel patient gown. You can contact her at [email protected]. Dr. Dellasega is based in the department of humanities, Penn State University, Hershey.
References
1. Lucas C et al. “Don’t let the gown get you down: How patients and providers perceive hospital gowns.” Abstract published at Hospital Medicine 2019, Mar 24-27, National Harbor, Md., Abstract 322.
2. Lucas C and Dellasega C. “You don’t have to be dying to do comfort measures: Patients’ and physicians’ perceptions of inpatient attire.” Abstract published at ACP Internal Medicine 2019, Apr 11-13, Philadelphia, Abstract.
3. Lucas C and Dellasega C. Finding common threads: How patients, physicians, and nurses perceive the patient gown. Patient Exp J. 2020;7(1):51-64.
4. Detsky A and Krumholtz H. Reducing the trauma of hospitalization. JAMA. 2014;311(21):2169-70.
5. Krumholz H. Post-hospital syndrome – an acquired, transient condition of generalized risk. N Engl J Med. 2013;368(2):100-2.
6. Wellbery C and Chan M. White coat, patient gown. Med Humanit. 2014;40(2):90-6.
7. McDonald E et al. Inpatient attire: An opportunity to improve the patient experience. JAMA Intern Med. 2014;174(11):1865-67.
8. Cogan N et al. Mixed methods study exploring the impact of the hospital gown on recovery and wellbeing: Implications for policy and practice. Lancet. 2019. doi: 10.1016/S0140-6736(19)32829-6.
9. Bergbom I, Pettersson M, and Mattsson E. Patient clothing – practical solution or means of imposing anonymity? J Hosp Med Manage. 2017;3(22):1-6.
10. Who invented the hospital gown? Interweave Healthcare. Accessed Mar 30, 2020.
11. Gordon L and Guttmann S. A user-centered approach to the redesign of the patient hospital gown. Fashion Practice. 2013;5(1):137-51. doi: 10.2752/175693813X13559997788961.
12. Limbong A. “Can a Patient Gown Makeover Move Hospitals to Embrace Change?” NPR. 2018 Feb 11. Accessed Mar 26, 2020.
13. Schiro A. “Patterns: Hospital Style.” New York Times. 1999 June 29. Accessed Mar 26, 2020.
14. Luthra S. “Hospital Gowns Get a Makeover.” The Atlantic. 2015 Apr 4. Accessed Mar 26, 2020.
15. Tien E. “Hospital Gowns Get a Life.” New York Times. 1998 Oct 18. Accessed Mar 26, 2020.
16. McCall-Smith K. United Nations Standard Minimum Rules for the Treatment of Prisoners (Nelson Mandela Rules). Int Leg Materials. 2016;55(6),1180-205.
17. Green C. “Updated hospital gowns a good investment, execs say, restore ‘dignity.’ ” Healthcare Finance. 2015 Aug 3. Accessed Apr 1, 2020.
“Don’t let the gown get you down,” was the advice a 26-year-old gentleman with leukemia offered in a study investigating the psychosocial impact of hospital gowns on patients and providers.1 Patients were found to be resigned to their “uncomfortable,” “expos[ing],” “nightmare-[ish]” “uniform,” afraid to even ask to wear more dignifying attire for fear of seeming difficult to providers and potentially harming the therapeutic relationship; one 64-year-old woman with terminal cancer detailed, “I have my own pajamas at home, but I don’t bring them because you can’t wear them here … [wearing a gown] is really not fun, but hey, this is what [providers] have to do, so it’s what you have to do.”1-3
Research has consistently shown that patients are vulnerable to dehumanization and loss of identity in the hospital, often exacerbated by wearing the standard hospital gown.3-8 Case in point, a mixed-methods study revealed that hospital gowns may lead to an increased sense of exposure, discomfort, disempowerment, and embarrassment for patients during a period of potential vulnerability while undergoing medical intervention.8
Hospital gowns strip autonomy from individuals humbly coming to the hospital for help. The gown has become a linchpin of change, initiating the dehumanizing process of “person” to “patient.” One of the main problems with the hospital gown is its exposing nature, often made light of on the wards with the joke, “Do you know who invented the hospital gown?…See-more Hiney!” The joke continued in two Super Bowl LIII commercials for a large academic health care system and insurance provider in Pennsylvania, depicting a construction worker and businessman clad in hospital gowns, mooning their less-than-pleased coworkers, to inform patients of expanded insurance coverage, i.e., “completely covered.” Hospital gowns are also a source of comedic fodder on sitcoms, including “It’s Always Sunny in Philadelphia,” “Man with a Plan,” and “Carol’s Second Act.”
It is common knowledge that hospital gowns are flawed, but very little has been done to change them. Little is known about the origin of hospital gowns, and like their design, their history has many gaps. PubMed, Google, and Wikipedia yield no fruitful insight into the evolution of the hospital gown, and perhaps the best way to understand the hospital gown over time is to watch depictions of patients in television sitcoms, dramas, and movies, ranging from the days of black-and-white into the modern era, and view artistic depictions of hospitals across eras. Case in point, depictions of fourteenth century hospital wards in art show that all patients wore night shirts, under which they also wore some type of underclothing.9 By the end of the 1800s and beginning of the 1900s, pajamas for men became more common as hospital attire.9 Although it is not known who originally invented the traditional hospital gown, the original gown was designed around a century ago with an open back for use on patients admitted the night prior to surgery, who were sedated prior to transfer to the anesthetic room while half-asleep.10
In general, the most common reason that hospitals began to provide, require, or offer clothing to patients was to reduce infection and improve hygiene, as clothing can be ruined by leakage of bodily fluids from various examinations, treatments, and procedures.9 In addition, in certain settings, lifesaving measures require access to the naked body to allow equipment, like a defibrillator, to be connected to the patient; a gown can theoretically be removed quickly.9 For some reason along the way, the simple, open-backed “johnny” gown of the early 20th century became standard of care with minimal meaningful modifications in the last hundred years. One possible explanation for the persistence of the “johnny” gown is that in past eras of medicine, patients in gowns were expected to be bedbound for recovery, keeping their bare bottom under wraps, and this norm became the status quo. Today, ambulation is encouraged in patients as part of venous thromboembolism (VTE) prophylaxis but the gown design has fallen behind.
Modern medicine emphasizes, values, and even advertises evidence-based medicine, patient-centered care, and high-quality care, yet the hospital gown stands as a stark contrast to this pledge to move forward as beacons of change. Hospital gowns have fallen outside of the scope of evidence-based research.11 One may ask why the gown remains decades behind modern medicine, and it appears that this apathy stems from (1) accepting “medical tradition” and choosing to overlook the flaws of the current hospital gown, and (2) believing that changing the hospital gown would cost money, affronting an institution’s almighty bottom-line. Still, several institutions have attempted change, including Hackensack University Medical Center partnering with Cynthia Rowley and Nicole Miller (1999), Cleveland Clinic partnering with Diane von Furstenberg (2010), and Henry Ford Health System of Detroit’s “Model G” gown (2016).12-15
In spite of these efforts to revamp the hospital gown at academic medical centers, change has been neither long lasting nor widely disseminated. Traci Lamar, a professor at the North Carolina State University College of Textiles reasoned that, “There are number of pressures in the hospital environment that influence what they purchase and when they purchase. Cost management, inventory management, storage space. ... There’s more value coming with the apparel item if it also becomes something that replaces or enhances other equipment that’s used in the hospital environment. Like a gown that can also keep an eye on your blood pressure or measure your heart rate.”15
The hospital gown remains a poor attempt at proper attire for human beings, with the most similar evolutionary relative being a hairdresser’s cape. Taken a step further, functionally the hospital gown is most similar to a prison uniform. Although this may seem bold and sensational, one must stop and think about it, considering the parallels. When individuals are admitted to the hospital, they exchange their clothing for a hospital gown, so that they can be easily identified as a “patient” and remain safe in the hospital. When individuals are sentenced to prison, they exchange their clothing for a uniform, so that they can be easily identified as a “prisoner” and remain safe in jail. The problem is, more time, money, and effort has gone into designing prisoners’ garments, who expect a loss of autonomy, than designing patients’ garments, who should never expect a loss of autonomy.
Prison uniforms are designed with safety in mind, ensuring the absence of potential ligatures or improvised weapons. The United Nations even passed an amendment to its Standard Minimum Rules for the Treatment of Prisoners in 2015, prohibiting humiliating clothing and requiring every prisoner who is “not allowed to wear his or her own clothing” to “be provided with an outfit of clothing suitable for the climate and adequate to keep him or her in good health.”16 They also stipulated that prisoners’ clothing could not be degrading or humiliating and was mandated to “be clean and kept in proper condition”.16 Even more compelling, a physician was bequeathed the task of inspecting, and advising the prison director on “the suitability and cleanliness of the prisoners’ clothing and bedding.”16 However, there are no standard minimum rules for hospital patients’ clothing. Hospital gowns have been described as “threadbare,” “one-size-fits-none,” “stained,” and “drafty,” antithetical to both hygiene and the hospital climate – far from “proper condition” (See Figure 1).1
Where are the standard minimum rules for hospital gowns? Patients have admittedly wondered, “What happened to the person who wore this gown before I did?” or worse, “Who died in this gown?” Even more, the current hospital gown can unintentionally put a patient in harms’ way, posing a fall risk for patients with petite frames overwhelmed by the bulk of the gown and also inhibiting fast access to the chest for placement of defibrillation pads in a code. Ironically, prison uniforms have the main things patients have requested: bottoms, modesty, multiple sizes, and … color!1-3
Although jailhouse orange or stripes are unlikely to be high fashion in the hospital, it is important to consider that, through indifference about the current hospital gown, institutions are teaching that it is acceptable for patients to wear this dehumanizing garment analogous to a prison uniform, except less colorful and more exposing. The hospital gown has persisted under the myth of medical tradition, masking the fact that there is neither evidence for the current hospital gown design nor data to support its functional success for patients or providers.3,12,14 Silence speaks volumes, and patients are taught to expect and accept a loss of dignity without questioning this archaic aspect of medical culture. Patients, nurses, and physicians do not challenge the status quo because the hospital gown “is the way it has always been done.” Perceived added-cost and medical tradition have further perpetuated the current open-backed hospital gown because meaningful change would require money.
With that said, “double gowning,” the method hospitals have used to combat lunar eclipses in the hallways and provide a semblance of dignity to patients, is already costing hospitals more money, costs that can be reduced by creating an evidence-based, patient-guided, provider-approved design. As Mike Forbes, the product designer and licensing associate for the Model G gown, argued, “By using two, you’re purchasing two gowns because one doesn’t do the job, which costs money. … If you’re washing twice as many gowns as you need, you’re spending twice as much money as you need on laundry.”17
Thus, improvements can be made without breaking the bank and may even save hospitals money in the long run. For instance, a hospital administrator can order more colors or styles of hospital gowns and bottoms to give patients a choice of what they would prefer to wear: a small piece of autonomy in an environment where minimal autonomy exists. A physician or nurse can not only permit, but also encourage, a patient to wear his or her own attire within reason, for example, a loose-fitting t-shirt and sweatpants from home or pajama pants under a hospital gown. More complex solutions could include a community design contest for a medical center’s new hospital gown print, or even bolder, a community design contest for a medical center’s new inpatient attire. Above all, patients need to know that hospitals and providers care about what patients wear in the hospital. As a terminally ill patient suggested, “maybe all administrators and office staff should have to spend one day in a gown. …They advertise this: ‘We always put the patient first.’ Okay, so then I guess you have to put your money where your mouth is.”3
This new decade offers the opportunity to give patients a sense of dignity back and make concerted, evidence-based efforts towards meaningful and sustainable change in patient attire, be it purchasing more colorful and modest gown options in the present or total redesign in the future. The financial cost may seem burdensome, but the reward would be immensely bountiful. It is time to stop making hospital gown–clad patients’ exposed bottoms the butt of the joke, and the only way to change the punchline is to change the hospital gown. Patients deserve more than the bare minimum and a bare bottom, so hospitals must consider putting their money where their mouth is.
Dr. Lucas is based in the department of pediatrics, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh. She has a provisional utility patent pending for a novel patient gown. You can contact her at [email protected]. Dr. Dellasega is based in the department of humanities, Penn State University, Hershey.
References
1. Lucas C et al. “Don’t let the gown get you down: How patients and providers perceive hospital gowns.” Abstract published at Hospital Medicine 2019, Mar 24-27, National Harbor, Md., Abstract 322.
2. Lucas C and Dellasega C. “You don’t have to be dying to do comfort measures: Patients’ and physicians’ perceptions of inpatient attire.” Abstract published at ACP Internal Medicine 2019, Apr 11-13, Philadelphia, Abstract.
3. Lucas C and Dellasega C. Finding common threads: How patients, physicians, and nurses perceive the patient gown. Patient Exp J. 2020;7(1):51-64.
4. Detsky A and Krumholtz H. Reducing the trauma of hospitalization. JAMA. 2014;311(21):2169-70.
5. Krumholz H. Post-hospital syndrome – an acquired, transient condition of generalized risk. N Engl J Med. 2013;368(2):100-2.
6. Wellbery C and Chan M. White coat, patient gown. Med Humanit. 2014;40(2):90-6.
7. McDonald E et al. Inpatient attire: An opportunity to improve the patient experience. JAMA Intern Med. 2014;174(11):1865-67.
8. Cogan N et al. Mixed methods study exploring the impact of the hospital gown on recovery and wellbeing: Implications for policy and practice. Lancet. 2019. doi: 10.1016/S0140-6736(19)32829-6.
9. Bergbom I, Pettersson M, and Mattsson E. Patient clothing – practical solution or means of imposing anonymity? J Hosp Med Manage. 2017;3(22):1-6.
10. Who invented the hospital gown? Interweave Healthcare. Accessed Mar 30, 2020.
11. Gordon L and Guttmann S. A user-centered approach to the redesign of the patient hospital gown. Fashion Practice. 2013;5(1):137-51. doi: 10.2752/175693813X13559997788961.
12. Limbong A. “Can a Patient Gown Makeover Move Hospitals to Embrace Change?” NPR. 2018 Feb 11. Accessed Mar 26, 2020.
13. Schiro A. “Patterns: Hospital Style.” New York Times. 1999 June 29. Accessed Mar 26, 2020.
14. Luthra S. “Hospital Gowns Get a Makeover.” The Atlantic. 2015 Apr 4. Accessed Mar 26, 2020.
15. Tien E. “Hospital Gowns Get a Life.” New York Times. 1998 Oct 18. Accessed Mar 26, 2020.
16. McCall-Smith K. United Nations Standard Minimum Rules for the Treatment of Prisoners (Nelson Mandela Rules). Int Leg Materials. 2016;55(6),1180-205.
17. Green C. “Updated hospital gowns a good investment, execs say, restore ‘dignity.’ ” Healthcare Finance. 2015 Aug 3. Accessed Apr 1, 2020.
Still no clear answer on intranasal insulin for MCI and Alzheimer’s disease
The randomized trial of nearly 300 patients showed that, although one insulin administration device produced marked benefit in terms of change in mean score on the Alzheimer Disease Assessment Scale–Cognitive Subscale 12 (ADAS-cog-12) over 12 months, reliability was inconsistent. A second device, used on the majority of patients in the study’s intention-to-treat population, showed no difference in these measures between patients who did and those who did not receive intranasal insulin.
“The primary analysis of the study showed no benefit of intranasal insulin on any measures of cognition or cerebrospinal fluid Alzheimer’s disease biomarkers when using the new device,” said principal investigator Suzanne Craft, PhD.
“But when we looked at our planned secondary analysis with the original device – which has been successful in previous studies – we saw quite a different picture,” added Dr. Craft, director of the Alzheimer’s Disease Research Center at Wake Forest University, Winston-Salem, N.C.
“We found a pronounced benefit with that device, such that after 18 months of administration, participants who had been receiving insulin from the beginning of the study had a large and clinically significant advantage in the primary outcome measure.”
Dr. Craft described the findings as complex. “The primary results were negative,” she added. “But the secondary results replicated those of several earlier studies when we used the same device that was used in those.”
The study was published online June 22 in JAMA Neurology.
Important for brain function
Insulin has been shown to play several important roles in brain function. The hormone is associated with a variety of cognitive functions, including memory. Through its association with vasoreactivity, lipid metabolism, and inflammation, insulin also plays an important role in vascular function.
“In the normal brain in healthy individuals, insulin is very important for synaptic function and viability. Insulin also promotes dendritic growth and facilitates synaptic health. Through this role, it plays an important part in memory,” said Dr. Craft. Given these connections, it is not surprising that reduced insulin levels or activity in brain and cerebrospinal fluid have been documented in some, but not all, studies of Alzheimer’s disease. Markers of insulin resistance also have been detected in both neuronally derived exosomes and brain tissue from adults with Alzheimer’s disease.
In light of the several important roles that insulin plays in the brain – coupled with the evidence connecting dysregulation of brain insulin and AD pathology – restoring brain insulin function may offer therapeutic benefit for adults suffering either Alzheimer’s disease or MCI. “There are a number of ways to do this,” said Dr. Craft. “But one of the approaches that we’ve focused on is providing insulin directly to the brain through intranasal administration. “By doing this, you circumvent potential issues if you administered insulin systemically.”
Previous research has shown that through this mode of administration, insulin can bypass the blood-brain barrier and reach the brain through olfactory and trigeminal perivascular channels, with little effect on peripheral insulin or blood glucose levels.
As previously reported, an earlier pilot study, also conducted by Dr. Craft and her team, showed that 4 months of daily intranasal administration of 20 IU or 40 IU of insulin preserved cognitive performance in individuals with Alzheimer’s disease or MCI.
Deeper dive
In the current investigation, the researchers wanted to broaden these findings in a larger, longer, randomized double-blinded clinical trial. The investigators assessed the efficacy of intranasal insulin on cognition, function, and biomarkers of Alzheimer’s disease, as well as the safety and feasibility of the delivery method. The multicenter trial was conducted from 2014 to 2018 and included 27 sites.
Study participants were between the ages of 55 and 85 years and had been diagnosed with amnestic MCI or Alzheimer’s disease on the basis of National Institute on Aging–Alzheimer Association criteria, a score of 20 or higher on the Mini–Mental State Examination, a clinical dementia rating of 0.5 or 1.0, or a delayed logical memory score within a specified range.
In total, 289 participants were randomly assigned to receive 40 IU of insulin or placebo for 12 months, followed by a 6-month open-label extension phase. The first 49 participants (32 men; mean age, 71.9 years) underwent insulin administration with the same device the investigators used in previous trials.
Of these, 45 completed the blinded phase, and 42 completed the open-label extension. When this device, which uses an electronic nebulizer-like delivery system, proved unreliable, the researchers switched to a second device, which uses a liquid hydrofluoroalkane propellant to deliver a metered dose of insulin through a nose tip without electronic assistance. Device 2 was used for the remaining 240 participants (123 men; mean age, 70.8 years). These patients became the study’s primary intention-to-treat population.
The study’s primary outcome was the mean change in score on the Alzheimer Disease Assessment Scale–Cognitive Subscale 12 (ADAS-cog-12), which was evaluated at 3-month intervals.
Secondary clinical outcomes were assessed at 6-month intervals. These included the mean change in scores for the Alzheimer Disease Cooperative Study Activities of Daily Living Scale for Mild Cognitive Impairment and the Clinical Dementia Rating Scale Sum of Boxes.
Safety and adherence were also assessed during each study visit. Physical and neurologic examinations were performed at baseline and at months 6, 12, and 18.
Of the primary intention-to-treat population of 240 patients, 121 were randomly assigned to receive intranasal insulin. The remaining 119 received placebo and served as controls. The two groups were demographically comparable.
Better cognitive performance
A total of 215 participants completed the blinded phase; 198 participants completed the open-label extension. Discontinuation rates were comparable in both arms. The researchers found no differences between groups with respect to mean change in ADAS-cog-12 score from baseline to month 12 (0.0258 points; 95% confidence interval, –1.771 to 1.822 points; P = .98). The two groups also proved comparable in terms of performance on all other cognitive tests.
The open-label portion yielded similar results. Participants originally assigned to the insulin arm and their counterparts in the placebo arm did not differ with respect to mean score change on the ADAS-cog-12 test (or any other outcome) at either month 15 or 18.
Cerebrospinal fluid insulin levels were unchanged between groups, as were blood glucose and hemoglobin A1c values. Indeed, levels of A-beta42, A-beta40, total tau protein, and tau p-181 were comparable for the patients who received intranasal insulin and those who received placebo.
The most common adverse events were infections, injuries, respiratory disorders, and nervous system disorders, though these did not differ between groups. In addition, there were no differences between groups with respect to severity of adverse events; most were rated as mild.
In contrast with the intention-to-treat population, the study’s secondary analysis – using data from the original administration device – yielded markedly different results. In the blinded phase, patients who received insulin had better ADAS-cog-12 performance at 12 months (−2.81 points; 95% CI, −6.09 to 0.45 points; P = .09) and nominally significant effects at 6 months (−3.78 points; 95% CI, −6.79 to −0.78 points; P = .01).
Device type critical
These effects persisted in the open-label analyses. Patients who received intranasal insulin had superior ADAS-cog-12 scores at month 15 (−5.70 points; 95% CI, −9.62 to −1.79 points; P = .004) and month 18 (−5.78 points; 95% CI, −10.55 to −1.01 points; P = .02), compared with their counterparts who received insulin via the second device. This part of the study also showed that, although individual biomarkers did not differ significantly between the two arms, the ratios of A-beta42 to A-beta40 (P = .01) and A-beta42 to total tau (P = .03) increased with use of the first device. The number, type, and severity of adverse events were comparable between the insulin and placebo groups in this arm of the study.
The mixed results revealed by the trial demonstrate that the device used for intranasal insulin administration is paramount in determining the therapy’s potential efficacy. “Our take-home message is that the device is a very important factor for these studies and that one needs to validate their ability to effectively deliver insulin to the CNS,” said Dr. Craft.
“We were quite confident that the first device was able to do that. On the other hand, the second device has never been tested in that way, and we still don’t know whether or not that device was able to successfully deliver insulin,” she said.
The investigators recognize the need for more research in the field. Such studies, Dr. Craft noted, will utilize administration devices that have been previously verified to have the ability to deliver insulin to the central nervous system. “We’re currently testing several devices,” she noted. “We’re using a protocol where we administer insulin with the devices and then conduct a lumbar puncture about 30 minutes later to verify that it is actually raising insulin levels in the cerebrospinal fluid.”
Not a failure
Commenting on the findings, Samuel E. Gandy, MD, PhD, who was not involved in the study, said the research illustrates the challenge when a new therapy, a new delivery device, and a cohort of cognitively impaired patients collide. “The result is not quite a slam dunk but is also by no means a failure,” commented Dr. Gandy, Mount Sinai Chair in Alzheimer’s Research at Mount Sinai Medical Center, New York.
“One looks forward to future iterations of the Craft et al. approach, wherein the trialists tweak the ligand and/or the delivery schedule and/or the device and/or the disease and/or the disease stage,” Dr. Gandy added. “Another ligand, VGF, also holds promise for intranasal delivery, based on work from Steve Salton, Michelle Ehrlich, and Eric Schadt, all from Mount Sinai. Perhaps the nose knows!”
For Dr. Craft, the potential upside of intranasal insulin for these patients is significant and warrants further investigation. “I understand why people who are not familiar with prior research in this area might be skeptical of our enthusiasm, given the results in the intention-to-treat population,” she said. “But those of us who have been working along with this for a while now, we feel like we’ve got to do the next study. But we need to have a device that we know works,” Dr. Craft added.
“If this is real, then there may be a very large clinical benefit in symptomatic patients, and there’s nothing so far that has really improved symptomatic disease.”
The study was supported by the National Institute on Aging. Eli Lilly provided diluent placebo for the blinded phase and insulin for the open-label phase of the clinical trial at no cost. Dr. Craft received grants from the National Institute on Aging and nonfinancial support from Eli Lilly during the conduct of the study and personal fees from T3D Therapeutics and vTv Therapeutics outside the submitted work.
A version of this article originally appeared on Medscape.com.
The randomized trial of nearly 300 patients showed that, although one insulin administration device produced marked benefit in terms of change in mean score on the Alzheimer Disease Assessment Scale–Cognitive Subscale 12 (ADAS-cog-12) over 12 months, reliability was inconsistent. A second device, used on the majority of patients in the study’s intention-to-treat population, showed no difference in these measures between patients who did and those who did not receive intranasal insulin.
“The primary analysis of the study showed no benefit of intranasal insulin on any measures of cognition or cerebrospinal fluid Alzheimer’s disease biomarkers when using the new device,” said principal investigator Suzanne Craft, PhD.
“But when we looked at our planned secondary analysis with the original device – which has been successful in previous studies – we saw quite a different picture,” added Dr. Craft, director of the Alzheimer’s Disease Research Center at Wake Forest University, Winston-Salem, N.C.
“We found a pronounced benefit with that device, such that after 18 months of administration, participants who had been receiving insulin from the beginning of the study had a large and clinically significant advantage in the primary outcome measure.”
Dr. Craft described the findings as complex. “The primary results were negative,” she added. “But the secondary results replicated those of several earlier studies when we used the same device that was used in those.”
The study was published online June 22 in JAMA Neurology.
Important for brain function
Insulin has been shown to play several important roles in brain function. The hormone is associated with a variety of cognitive functions, including memory. Through its association with vasoreactivity, lipid metabolism, and inflammation, insulin also plays an important role in vascular function.
“In the normal brain in healthy individuals, insulin is very important for synaptic function and viability. Insulin also promotes dendritic growth and facilitates synaptic health. Through this role, it plays an important part in memory,” said Dr. Craft. Given these connections, it is not surprising that reduced insulin levels or activity in brain and cerebrospinal fluid have been documented in some, but not all, studies of Alzheimer’s disease. Markers of insulin resistance also have been detected in both neuronally derived exosomes and brain tissue from adults with Alzheimer’s disease.
In light of the several important roles that insulin plays in the brain – coupled with the evidence connecting dysregulation of brain insulin and AD pathology – restoring brain insulin function may offer therapeutic benefit for adults suffering either Alzheimer’s disease or MCI. “There are a number of ways to do this,” said Dr. Craft. “But one of the approaches that we’ve focused on is providing insulin directly to the brain through intranasal administration. “By doing this, you circumvent potential issues if you administered insulin systemically.”
Previous research has shown that through this mode of administration, insulin can bypass the blood-brain barrier and reach the brain through olfactory and trigeminal perivascular channels, with little effect on peripheral insulin or blood glucose levels.
As previously reported, an earlier pilot study, also conducted by Dr. Craft and her team, showed that 4 months of daily intranasal administration of 20 IU or 40 IU of insulin preserved cognitive performance in individuals with Alzheimer’s disease or MCI.
Deeper dive
In the current investigation, the researchers wanted to broaden these findings in a larger, longer, randomized double-blinded clinical trial. The investigators assessed the efficacy of intranasal insulin on cognition, function, and biomarkers of Alzheimer’s disease, as well as the safety and feasibility of the delivery method. The multicenter trial was conducted from 2014 to 2018 and included 27 sites.
Study participants were between the ages of 55 and 85 years and had been diagnosed with amnestic MCI or Alzheimer’s disease on the basis of National Institute on Aging–Alzheimer Association criteria, a score of 20 or higher on the Mini–Mental State Examination, a clinical dementia rating of 0.5 or 1.0, or a delayed logical memory score within a specified range.
In total, 289 participants were randomly assigned to receive 40 IU of insulin or placebo for 12 months, followed by a 6-month open-label extension phase. The first 49 participants (32 men; mean age, 71.9 years) underwent insulin administration with the same device the investigators used in previous trials.
Of these, 45 completed the blinded phase, and 42 completed the open-label extension. When this device, which uses an electronic nebulizer-like delivery system, proved unreliable, the researchers switched to a second device, which uses a liquid hydrofluoroalkane propellant to deliver a metered dose of insulin through a nose tip without electronic assistance. Device 2 was used for the remaining 240 participants (123 men; mean age, 70.8 years). These patients became the study’s primary intention-to-treat population.
The study’s primary outcome was the mean change in score on the Alzheimer Disease Assessment Scale–Cognitive Subscale 12 (ADAS-cog-12), which was evaluated at 3-month intervals.
Secondary clinical outcomes were assessed at 6-month intervals. These included the mean change in scores for the Alzheimer Disease Cooperative Study Activities of Daily Living Scale for Mild Cognitive Impairment and the Clinical Dementia Rating Scale Sum of Boxes.
Safety and adherence were also assessed during each study visit. Physical and neurologic examinations were performed at baseline and at months 6, 12, and 18.
Of the primary intention-to-treat population of 240 patients, 121 were randomly assigned to receive intranasal insulin. The remaining 119 received placebo and served as controls. The two groups were demographically comparable.
Better cognitive performance
A total of 215 participants completed the blinded phase; 198 participants completed the open-label extension. Discontinuation rates were comparable in both arms. The researchers found no differences between groups with respect to mean change in ADAS-cog-12 score from baseline to month 12 (0.0258 points; 95% confidence interval, –1.771 to 1.822 points; P = .98). The two groups also proved comparable in terms of performance on all other cognitive tests.
The open-label portion yielded similar results. Participants originally assigned to the insulin arm and their counterparts in the placebo arm did not differ with respect to mean score change on the ADAS-cog-12 test (or any other outcome) at either month 15 or 18.
Cerebrospinal fluid insulin levels were unchanged between groups, as were blood glucose and hemoglobin A1c values. Indeed, levels of A-beta42, A-beta40, total tau protein, and tau p-181 were comparable for the patients who received intranasal insulin and those who received placebo.
The most common adverse events were infections, injuries, respiratory disorders, and nervous system disorders, though these did not differ between groups. In addition, there were no differences between groups with respect to severity of adverse events; most were rated as mild.
In contrast with the intention-to-treat population, the study’s secondary analysis – using data from the original administration device – yielded markedly different results. In the blinded phase, patients who received insulin had better ADAS-cog-12 performance at 12 months (−2.81 points; 95% CI, −6.09 to 0.45 points; P = .09) and nominally significant effects at 6 months (−3.78 points; 95% CI, −6.79 to −0.78 points; P = .01).
Device type critical
These effects persisted in the open-label analyses. Patients who received intranasal insulin had superior ADAS-cog-12 scores at month 15 (−5.70 points; 95% CI, −9.62 to −1.79 points; P = .004) and month 18 (−5.78 points; 95% CI, −10.55 to −1.01 points; P = .02), compared with their counterparts who received insulin via the second device. This part of the study also showed that, although individual biomarkers did not differ significantly between the two arms, the ratios of A-beta42 to A-beta40 (P = .01) and A-beta42 to total tau (P = .03) increased with use of the first device. The number, type, and severity of adverse events were comparable between the insulin and placebo groups in this arm of the study.
The mixed results revealed by the trial demonstrate that the device used for intranasal insulin administration is paramount in determining the therapy’s potential efficacy. “Our take-home message is that the device is a very important factor for these studies and that one needs to validate their ability to effectively deliver insulin to the CNS,” said Dr. Craft.
“We were quite confident that the first device was able to do that. On the other hand, the second device has never been tested in that way, and we still don’t know whether or not that device was able to successfully deliver insulin,” she said.
The investigators recognize the need for more research in the field. Such studies, Dr. Craft noted, will utilize administration devices that have been previously verified to have the ability to deliver insulin to the central nervous system. “We’re currently testing several devices,” she noted. “We’re using a protocol where we administer insulin with the devices and then conduct a lumbar puncture about 30 minutes later to verify that it is actually raising insulin levels in the cerebrospinal fluid.”
Not a failure
Commenting on the findings, Samuel E. Gandy, MD, PhD, who was not involved in the study, said the research illustrates the challenge when a new therapy, a new delivery device, and a cohort of cognitively impaired patients collide. “The result is not quite a slam dunk but is also by no means a failure,” commented Dr. Gandy, Mount Sinai Chair in Alzheimer’s Research at Mount Sinai Medical Center, New York.
“One looks forward to future iterations of the Craft et al. approach, wherein the trialists tweak the ligand and/or the delivery schedule and/or the device and/or the disease and/or the disease stage,” Dr. Gandy added. “Another ligand, VGF, also holds promise for intranasal delivery, based on work from Steve Salton, Michelle Ehrlich, and Eric Schadt, all from Mount Sinai. Perhaps the nose knows!”
For Dr. Craft, the potential upside of intranasal insulin for these patients is significant and warrants further investigation. “I understand why people who are not familiar with prior research in this area might be skeptical of our enthusiasm, given the results in the intention-to-treat population,” she said. “But those of us who have been working along with this for a while now, we feel like we’ve got to do the next study. But we need to have a device that we know works,” Dr. Craft added.
“If this is real, then there may be a very large clinical benefit in symptomatic patients, and there’s nothing so far that has really improved symptomatic disease.”
The study was supported by the National Institute on Aging. Eli Lilly provided diluent placebo for the blinded phase and insulin for the open-label phase of the clinical trial at no cost. Dr. Craft received grants from the National Institute on Aging and nonfinancial support from Eli Lilly during the conduct of the study and personal fees from T3D Therapeutics and vTv Therapeutics outside the submitted work.
A version of this article originally appeared on Medscape.com.
The randomized trial of nearly 300 patients showed that, although one insulin administration device produced marked benefit in terms of change in mean score on the Alzheimer Disease Assessment Scale–Cognitive Subscale 12 (ADAS-cog-12) over 12 months, reliability was inconsistent. A second device, used on the majority of patients in the study’s intention-to-treat population, showed no difference in these measures between patients who did and those who did not receive intranasal insulin.
“The primary analysis of the study showed no benefit of intranasal insulin on any measures of cognition or cerebrospinal fluid Alzheimer’s disease biomarkers when using the new device,” said principal investigator Suzanne Craft, PhD.
“But when we looked at our planned secondary analysis with the original device – which has been successful in previous studies – we saw quite a different picture,” added Dr. Craft, director of the Alzheimer’s Disease Research Center at Wake Forest University, Winston-Salem, N.C.
“We found a pronounced benefit with that device, such that after 18 months of administration, participants who had been receiving insulin from the beginning of the study had a large and clinically significant advantage in the primary outcome measure.”
Dr. Craft described the findings as complex. “The primary results were negative,” she added. “But the secondary results replicated those of several earlier studies when we used the same device that was used in those.”
The study was published online June 22 in JAMA Neurology.
Important for brain function
Insulin has been shown to play several important roles in brain function. The hormone is associated with a variety of cognitive functions, including memory. Through its association with vasoreactivity, lipid metabolism, and inflammation, insulin also plays an important role in vascular function.
“In the normal brain in healthy individuals, insulin is very important for synaptic function and viability. Insulin also promotes dendritic growth and facilitates synaptic health. Through this role, it plays an important part in memory,” said Dr. Craft. Given these connections, it is not surprising that reduced insulin levels or activity in brain and cerebrospinal fluid have been documented in some, but not all, studies of Alzheimer’s disease. Markers of insulin resistance also have been detected in both neuronally derived exosomes and brain tissue from adults with Alzheimer’s disease.
In light of the several important roles that insulin plays in the brain – coupled with the evidence connecting dysregulation of brain insulin and AD pathology – restoring brain insulin function may offer therapeutic benefit for adults suffering either Alzheimer’s disease or MCI. “There are a number of ways to do this,” said Dr. Craft. “But one of the approaches that we’ve focused on is providing insulin directly to the brain through intranasal administration. “By doing this, you circumvent potential issues if you administered insulin systemically.”
Previous research has shown that through this mode of administration, insulin can bypass the blood-brain barrier and reach the brain through olfactory and trigeminal perivascular channels, with little effect on peripheral insulin or blood glucose levels.
As previously reported, an earlier pilot study, also conducted by Dr. Craft and her team, showed that 4 months of daily intranasal administration of 20 IU or 40 IU of insulin preserved cognitive performance in individuals with Alzheimer’s disease or MCI.
Deeper dive
In the current investigation, the researchers wanted to broaden these findings in a larger, longer, randomized double-blinded clinical trial. The investigators assessed the efficacy of intranasal insulin on cognition, function, and biomarkers of Alzheimer’s disease, as well as the safety and feasibility of the delivery method. The multicenter trial was conducted from 2014 to 2018 and included 27 sites.
Study participants were between the ages of 55 and 85 years and had been diagnosed with amnestic MCI or Alzheimer’s disease on the basis of National Institute on Aging–Alzheimer Association criteria, a score of 20 or higher on the Mini–Mental State Examination, a clinical dementia rating of 0.5 or 1.0, or a delayed logical memory score within a specified range.
In total, 289 participants were randomly assigned to receive 40 IU of insulin or placebo for 12 months, followed by a 6-month open-label extension phase. The first 49 participants (32 men; mean age, 71.9 years) underwent insulin administration with the same device the investigators used in previous trials.
Of these, 45 completed the blinded phase, and 42 completed the open-label extension. When this device, which uses an electronic nebulizer-like delivery system, proved unreliable, the researchers switched to a second device, which uses a liquid hydrofluoroalkane propellant to deliver a metered dose of insulin through a nose tip without electronic assistance. Device 2 was used for the remaining 240 participants (123 men; mean age, 70.8 years). These patients became the study’s primary intention-to-treat population.
The study’s primary outcome was the mean change in score on the Alzheimer Disease Assessment Scale–Cognitive Subscale 12 (ADAS-cog-12), which was evaluated at 3-month intervals.
Secondary clinical outcomes were assessed at 6-month intervals. These included the mean change in scores for the Alzheimer Disease Cooperative Study Activities of Daily Living Scale for Mild Cognitive Impairment and the Clinical Dementia Rating Scale Sum of Boxes.
Safety and adherence were also assessed during each study visit. Physical and neurologic examinations were performed at baseline and at months 6, 12, and 18.
Of the primary intention-to-treat population of 240 patients, 121 were randomly assigned to receive intranasal insulin. The remaining 119 received placebo and served as controls. The two groups were demographically comparable.
Better cognitive performance
A total of 215 participants completed the blinded phase; 198 participants completed the open-label extension. Discontinuation rates were comparable in both arms. The researchers found no differences between groups with respect to mean change in ADAS-cog-12 score from baseline to month 12 (0.0258 points; 95% confidence interval, –1.771 to 1.822 points; P = .98). The two groups also proved comparable in terms of performance on all other cognitive tests.
The open-label portion yielded similar results. Participants originally assigned to the insulin arm and their counterparts in the placebo arm did not differ with respect to mean score change on the ADAS-cog-12 test (or any other outcome) at either month 15 or 18.
Cerebrospinal fluid insulin levels were unchanged between groups, as were blood glucose and hemoglobin A1c values. Indeed, levels of A-beta42, A-beta40, total tau protein, and tau p-181 were comparable for the patients who received intranasal insulin and those who received placebo.
The most common adverse events were infections, injuries, respiratory disorders, and nervous system disorders, though these did not differ between groups. In addition, there were no differences between groups with respect to severity of adverse events; most were rated as mild.
In contrast with the intention-to-treat population, the study’s secondary analysis – using data from the original administration device – yielded markedly different results. In the blinded phase, patients who received insulin had better ADAS-cog-12 performance at 12 months (−2.81 points; 95% CI, −6.09 to 0.45 points; P = .09) and nominally significant effects at 6 months (−3.78 points; 95% CI, −6.79 to −0.78 points; P = .01).
Device type critical
These effects persisted in the open-label analyses. Patients who received intranasal insulin had superior ADAS-cog-12 scores at month 15 (−5.70 points; 95% CI, −9.62 to −1.79 points; P = .004) and month 18 (−5.78 points; 95% CI, −10.55 to −1.01 points; P = .02), compared with their counterparts who received insulin via the second device. This part of the study also showed that, although individual biomarkers did not differ significantly between the two arms, the ratios of A-beta42 to A-beta40 (P = .01) and A-beta42 to total tau (P = .03) increased with use of the first device. The number, type, and severity of adverse events were comparable between the insulin and placebo groups in this arm of the study.
The mixed results revealed by the trial demonstrate that the device used for intranasal insulin administration is paramount in determining the therapy’s potential efficacy. “Our take-home message is that the device is a very important factor for these studies and that one needs to validate their ability to effectively deliver insulin to the CNS,” said Dr. Craft.
“We were quite confident that the first device was able to do that. On the other hand, the second device has never been tested in that way, and we still don’t know whether or not that device was able to successfully deliver insulin,” she said.
The investigators recognize the need for more research in the field. Such studies, Dr. Craft noted, will utilize administration devices that have been previously verified to have the ability to deliver insulin to the central nervous system. “We’re currently testing several devices,” she noted. “We’re using a protocol where we administer insulin with the devices and then conduct a lumbar puncture about 30 minutes later to verify that it is actually raising insulin levels in the cerebrospinal fluid.”
Not a failure
Commenting on the findings, Samuel E. Gandy, MD, PhD, who was not involved in the study, said the research illustrates the challenge when a new therapy, a new delivery device, and a cohort of cognitively impaired patients collide. “The result is not quite a slam dunk but is also by no means a failure,” commented Dr. Gandy, Mount Sinai Chair in Alzheimer’s Research at Mount Sinai Medical Center, New York.
“One looks forward to future iterations of the Craft et al. approach, wherein the trialists tweak the ligand and/or the delivery schedule and/or the device and/or the disease and/or the disease stage,” Dr. Gandy added. “Another ligand, VGF, also holds promise for intranasal delivery, based on work from Steve Salton, Michelle Ehrlich, and Eric Schadt, all from Mount Sinai. Perhaps the nose knows!”
For Dr. Craft, the potential upside of intranasal insulin for these patients is significant and warrants further investigation. “I understand why people who are not familiar with prior research in this area might be skeptical of our enthusiasm, given the results in the intention-to-treat population,” she said. “But those of us who have been working along with this for a while now, we feel like we’ve got to do the next study. But we need to have a device that we know works,” Dr. Craft added.
“If this is real, then there may be a very large clinical benefit in symptomatic patients, and there’s nothing so far that has really improved symptomatic disease.”
The study was supported by the National Institute on Aging. Eli Lilly provided diluent placebo for the blinded phase and insulin for the open-label phase of the clinical trial at no cost. Dr. Craft received grants from the National Institute on Aging and nonfinancial support from Eli Lilly during the conduct of the study and personal fees from T3D Therapeutics and vTv Therapeutics outside the submitted work.
A version of this article originally appeared on Medscape.com.
FROM JAMA NEUROLOGY
COVID-19 pandemic dictates reconsideration of pemphigus therapy
The Dedee F. Murrell, MD, said at the virtual annual meeting of the American Academy of Dermatology.
Together with physicians from the Mayo Clinic, Alexandria (Egypt) University, and Tehran (Iran) University, she recently published updated expert guidance for treatment of this severe, potentially fatal mucocutaneous autoimmune blistering disease, in a letter to the editor in the Journal of the American Academy of Dermatology. She presented some of the key recommendations at AAD 2020.
First off, rituximab (Rituxan), the only Food and Drug Administration–approved medication for moderate to severe pemphigus vulgaris and a biologic considered first-line therapy prepandemic, is ill-advised during the COVID-19 era. Its mechanism of benefit is through B-cell depletion. This is an irreversible effect, and reconstitution of B-cell immunity takes 6-12 months. The absence of this immunologic protection for such a long time poses potentially serious problems for pemphigus patients who become infected with SARS-CoV-2.
Also, the opportunity to administer intravenous infusions of the biologic becomes unpredictable during pandemic surges, when limitations on nonemergent medical care may be necessary, noted Dr. Murrell, professor of dermatology at the University of New South Wales and head of dermatology at St. George University Hospital, both in Sydney.
“We have taken the approach of postponing rituximab infusions temporarily, with the aim of delaying peak patient immunosuppression during peak COVID-19 incidence to reduce the risk of adverse outcomes,” Dr. Murrell and coauthors wrote in the letter (J Am Acad Dermatol. 2020 Jun;82[6]:e235-6).
The other traditional go-to therapy for pemphigus is corticosteroids. They’re effective, fast acting, and relatively inexpensive. But their nonselective immunosuppressive action boosts infection risk in general, and more specifically it increases the risk of developing severe forms of COVID-19 should a patient become infected with SARS-CoV-2.
“A basic therapeutic principle with particular importance during the pandemic is that glucocorticoids and steroid-sparing immunosuppressive agents, such as azathioprine and mycophenolate mofetil, should be tapered to the lowest effective dose. In active COVID-19 infection, immunosuppressive steroid-sparing medications should be discontinued when possible, although glucocorticoid cessation often cannot be considered due to risk for adrenal insufficiency,” the authors continued.
“Effective as adjuvant treatment in both pemphigus and COVID-19,intravenous immunoglobulin supports immunity and therefore may be useful in this setting,” they wrote. It’s not immunosuppressive, and, they noted, there’s good-quality evidence from a Japanese randomized, double-blind, controlled trial that a 5-day course of intravenous immunoglobulin is effective therapy for pemphigus (J Am Acad Dermatol. 2009 Apr;60[4]:595-603).
Moreover, intravenous immunoglobulin is also reportedly effective in severe COVID-19 (Open Forum Infect Dis. 2020 Mar 21. doi: 10.1093/ofid/ofaa102.).
Another option is to consider enrolling a patient with moderate or severe pemphigus vulgaris or foliaceus in the ongoing pivotal phase 3, international, double-blind, placebo-controlled PEGASUS trial of rilzabrutinib, a promising oral reversible Bruton tyrosine kinase inhibitor. The medication has a short half-life and a self-limited immunomodulatory effect. Moreover, the trial is set up for remote patient visits on an outpatient basis via teledermatology, so the 65-week study can continue despite the pandemic. Both newly diagnosed and relapsing patients are eligible for the trial, headed by Dr. Murrell. At AAD 2020 she reported encouraging results from a phase 2b trial of rilzabrutinib.
She is a consultant to Principia Biopharma, sponsor of the PEGASUS trial, and has received institutional research grants from numerous pharmaceutical companies.
The Dedee F. Murrell, MD, said at the virtual annual meeting of the American Academy of Dermatology.
Together with physicians from the Mayo Clinic, Alexandria (Egypt) University, and Tehran (Iran) University, she recently published updated expert guidance for treatment of this severe, potentially fatal mucocutaneous autoimmune blistering disease, in a letter to the editor in the Journal of the American Academy of Dermatology. She presented some of the key recommendations at AAD 2020.
First off, rituximab (Rituxan), the only Food and Drug Administration–approved medication for moderate to severe pemphigus vulgaris and a biologic considered first-line therapy prepandemic, is ill-advised during the COVID-19 era. Its mechanism of benefit is through B-cell depletion. This is an irreversible effect, and reconstitution of B-cell immunity takes 6-12 months. The absence of this immunologic protection for such a long time poses potentially serious problems for pemphigus patients who become infected with SARS-CoV-2.
Also, the opportunity to administer intravenous infusions of the biologic becomes unpredictable during pandemic surges, when limitations on nonemergent medical care may be necessary, noted Dr. Murrell, professor of dermatology at the University of New South Wales and head of dermatology at St. George University Hospital, both in Sydney.
“We have taken the approach of postponing rituximab infusions temporarily, with the aim of delaying peak patient immunosuppression during peak COVID-19 incidence to reduce the risk of adverse outcomes,” Dr. Murrell and coauthors wrote in the letter (J Am Acad Dermatol. 2020 Jun;82[6]:e235-6).
The other traditional go-to therapy for pemphigus is corticosteroids. They’re effective, fast acting, and relatively inexpensive. But their nonselective immunosuppressive action boosts infection risk in general, and more specifically it increases the risk of developing severe forms of COVID-19 should a patient become infected with SARS-CoV-2.
“A basic therapeutic principle with particular importance during the pandemic is that glucocorticoids and steroid-sparing immunosuppressive agents, such as azathioprine and mycophenolate mofetil, should be tapered to the lowest effective dose. In active COVID-19 infection, immunosuppressive steroid-sparing medications should be discontinued when possible, although glucocorticoid cessation often cannot be considered due to risk for adrenal insufficiency,” the authors continued.
“Effective as adjuvant treatment in both pemphigus and COVID-19,intravenous immunoglobulin supports immunity and therefore may be useful in this setting,” they wrote. It’s not immunosuppressive, and, they noted, there’s good-quality evidence from a Japanese randomized, double-blind, controlled trial that a 5-day course of intravenous immunoglobulin is effective therapy for pemphigus (J Am Acad Dermatol. 2009 Apr;60[4]:595-603).
Moreover, intravenous immunoglobulin is also reportedly effective in severe COVID-19 (Open Forum Infect Dis. 2020 Mar 21. doi: 10.1093/ofid/ofaa102.).
Another option is to consider enrolling a patient with moderate or severe pemphigus vulgaris or foliaceus in the ongoing pivotal phase 3, international, double-blind, placebo-controlled PEGASUS trial of rilzabrutinib, a promising oral reversible Bruton tyrosine kinase inhibitor. The medication has a short half-life and a self-limited immunomodulatory effect. Moreover, the trial is set up for remote patient visits on an outpatient basis via teledermatology, so the 65-week study can continue despite the pandemic. Both newly diagnosed and relapsing patients are eligible for the trial, headed by Dr. Murrell. At AAD 2020 she reported encouraging results from a phase 2b trial of rilzabrutinib.
She is a consultant to Principia Biopharma, sponsor of the PEGASUS trial, and has received institutional research grants from numerous pharmaceutical companies.
The Dedee F. Murrell, MD, said at the virtual annual meeting of the American Academy of Dermatology.
Together with physicians from the Mayo Clinic, Alexandria (Egypt) University, and Tehran (Iran) University, she recently published updated expert guidance for treatment of this severe, potentially fatal mucocutaneous autoimmune blistering disease, in a letter to the editor in the Journal of the American Academy of Dermatology. She presented some of the key recommendations at AAD 2020.
First off, rituximab (Rituxan), the only Food and Drug Administration–approved medication for moderate to severe pemphigus vulgaris and a biologic considered first-line therapy prepandemic, is ill-advised during the COVID-19 era. Its mechanism of benefit is through B-cell depletion. This is an irreversible effect, and reconstitution of B-cell immunity takes 6-12 months. The absence of this immunologic protection for such a long time poses potentially serious problems for pemphigus patients who become infected with SARS-CoV-2.
Also, the opportunity to administer intravenous infusions of the biologic becomes unpredictable during pandemic surges, when limitations on nonemergent medical care may be necessary, noted Dr. Murrell, professor of dermatology at the University of New South Wales and head of dermatology at St. George University Hospital, both in Sydney.
“We have taken the approach of postponing rituximab infusions temporarily, with the aim of delaying peak patient immunosuppression during peak COVID-19 incidence to reduce the risk of adverse outcomes,” Dr. Murrell and coauthors wrote in the letter (J Am Acad Dermatol. 2020 Jun;82[6]:e235-6).
The other traditional go-to therapy for pemphigus is corticosteroids. They’re effective, fast acting, and relatively inexpensive. But their nonselective immunosuppressive action boosts infection risk in general, and more specifically it increases the risk of developing severe forms of COVID-19 should a patient become infected with SARS-CoV-2.
“A basic therapeutic principle with particular importance during the pandemic is that glucocorticoids and steroid-sparing immunosuppressive agents, such as azathioprine and mycophenolate mofetil, should be tapered to the lowest effective dose. In active COVID-19 infection, immunosuppressive steroid-sparing medications should be discontinued when possible, although glucocorticoid cessation often cannot be considered due to risk for adrenal insufficiency,” the authors continued.
“Effective as adjuvant treatment in both pemphigus and COVID-19,intravenous immunoglobulin supports immunity and therefore may be useful in this setting,” they wrote. It’s not immunosuppressive, and, they noted, there’s good-quality evidence from a Japanese randomized, double-blind, controlled trial that a 5-day course of intravenous immunoglobulin is effective therapy for pemphigus (J Am Acad Dermatol. 2009 Apr;60[4]:595-603).
Moreover, intravenous immunoglobulin is also reportedly effective in severe COVID-19 (Open Forum Infect Dis. 2020 Mar 21. doi: 10.1093/ofid/ofaa102.).
Another option is to consider enrolling a patient with moderate or severe pemphigus vulgaris or foliaceus in the ongoing pivotal phase 3, international, double-blind, placebo-controlled PEGASUS trial of rilzabrutinib, a promising oral reversible Bruton tyrosine kinase inhibitor. The medication has a short half-life and a self-limited immunomodulatory effect. Moreover, the trial is set up for remote patient visits on an outpatient basis via teledermatology, so the 65-week study can continue despite the pandemic. Both newly diagnosed and relapsing patients are eligible for the trial, headed by Dr. Murrell. At AAD 2020 she reported encouraging results from a phase 2b trial of rilzabrutinib.
She is a consultant to Principia Biopharma, sponsor of the PEGASUS trial, and has received institutional research grants from numerous pharmaceutical companies.
FROM AAD 20
PD-1 Signaling in Extramammary Paget Disease
Primary extramammary Paget disease (EMPD) is an adnexal carcinoma of the apocrine gland ducts that presents as an erythematous patch on cutaneous sites rich with apocrine glands.1 Primary EMPD can be in situ or invasive with the potential to become metastatic.2 Treatment of primary EMPD is challenging due to the difficulty of achieving clear surgical margins, as the tumor has microscopic spread throughout the epidermis in a skipping fashion.3 Mohs micrographic surgery is the treatment of choice; however, there is a clinical need to identify additional treatment modalities, especially for patients with unresectable, invasive, or metastatic primary EMPD,4 which partly is due to lack of data to understand the pathogenesis of primary EMPD. Recently, there have been studies investigating the genetic characteristics of EMPD tumors. The interaction between the programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) is one of the pathways recently studied and has been reported to be a potential target in EMPD.5-7 Programmed cell death receptor 1 signaling constitutes an immune checkpoint pathway that regulates the activation of tumor-specific T cells.8 In several malignancies, cancer cells express PD-L1 on their surface to activate PD-1 signaling in T cells as a mechanism to dampen the tumor-specific immune response and evade antitumor immunity.9 Thus, blocking PD-1 signaling widely is used to activate tumor-specific T cells and decrease tumor burden.10 Given the advances of immunotherapy in many neoplasms and the paucity of effective agents to treat EMPD, this article serves to shed light on recent data studying PD-1 signaling in EMPD and highlights the potential clinical use of immunotherapy for EMPD.
EMPD and Its Subtypes
Extramammary Paget disease is a rare adenocarcinoma typically affecting older patients (age >60 years) in cutaneous sites with abundant apocrine glands such as the genital and perianal skin.3 Extramammary Paget disease presents as an erythematous patch and frequently is treated initially as a skin dermatosis, resulting in a delay in diagnosis. Histologically, EMPD is characterized by the presence of single cells or a nest of cells having abundant pale cytoplasm and large vesicular nuclei distributed in the epidermis in a pagetoid fashion.11
Extramammary Paget disease can be primary or secondary; the 2 subtypes behave differently both clinically and prognostically. Although primary EMPD is considered to be an adnexal carcinoma of the apocrine gland ducts, secondary EMPD is considered to be an intraepithelial extension of malignant cells from an underlying internal neoplasm.12 The underlying malignancies usually are located within dermal adnexal glands or organs in the vicinity of the cutaneous lesion, such as the colon in the case of perianal EMPD. Histologically, primary and secondary EMPD can be differentiated based on their immunophenotypic staining profiles. Although all cases of EMPD show positive immunohistochemistry staining for cytokeratin 7, carcinoembryonic antigen, and epithelial membrane antigen, only primary EMPD will additionally stain for GCDFP-15 (gross cystic disease fluid protein 15) and GATA.11 Regardless of the immunohistochemistry stains, every patient newly diagnosed with EMPD deserves a full workup for malignancy screening, including a colonoscopy, cystoscopy, mammography and Papanicolaou test in women, pelvic ultrasound, and computed tomography of the abdomen and pelvis.13
The first-line treatment of EMPD is surgery; however, obtaining clear surgical margins can be a challenge, with high recurrence rates due to the microscopic spread of the disease throughout the epidermis.4 In addition, anatomic location affects the surgical approach and patient survival. Recent studies on EMPD mortality outcomes in women show that mortality is higher in patients with vaginal EMPD than in those with vulvar/labial EMPD, partly due to the sensitive location that makes it difficult to perform wide local excisions.13,14 Assessing the entire margins with tissue preservation using Mohs micrographic surgery has been shown to be successful in decreasing the recurrence rate, especially when coupled with the use of cytokeratin 7 immunohistochemistry.4 Other treatment modalities include radiation, topical imiquimod, and photodynamic therapy.15,16 Regardless of treatment modality, EMPD requires long‐term follow-up to monitor for disease recurrence, regional lymphadenopathy, distant metastasis, or development of an internal malignancy.
The pathogenesis of primary EMPD remains unclear. The tumor is thought to be derived from Toker cells, which are pluripotent adnexal stem cells located in the epidermis that normally give rise to apocrine glands.17 There have been few studies investigating the genetic characteristics of EMPD lesions in an attempt to understand pathogenesis as well as to find druggable targets. Current data for targeted therapy have focused on HER2 (human epidermal growth factor receptor 2) hormone receptor expression,18 ERBB (erythroblastic oncogene B) amplification,19 CDK4 (cyclin-dependent kinase 4)–cyclin D1 signaling,20 and most recently PD-1/PD-L1 pathway.5-7
PD-1 Expression in EMPD: Implication for Immunotherapy
Most tumors display novel antigens that are recognized by the host immune system and thus stimulate cell-mediated and humoral pathways. The immune system naturally provides regulatory immune checkpoints to T cell–mediated immune responses. One of these checkpoints involves the interaction between PD-1 on T cells and its ligand PD-L1 on tumor cells.21 When PD-1 binds to PD-L1 on tumor cells, there is inhibition of T-cell proliferation, a decrease in cytokine production, and induction of T-cell cytolysis.22 The Figure summarizes the dynamics for T-cell regulation.
Naturally, tumor-infiltrating T cells trigger their own inhibition by binding to PD-L1. However, certain tumor cells constitutively upregulate the expression of PD-L1. With that, the tumor cells gain the ability to suppress T cells and avoid T cell–mediated cytotoxicity,23 which is known as the adoptive immune resistance mechanism. There have been several studies in the literature investigating the PD-1 signaling pathway in EMPD as a way to determine if EMPD would be susceptible to immune checkpoint blockade. The success of checkpoint inhibitor immunotherapy generally correlates with increased PD-L1 expression by tumor cells.
One study evaluated the expression of PD-L1 in tumor cells and tumor-infiltrating T cells in 18 cases of EMPD.6 The authors identified that even though tumor cell PD-L1 expression was detected in only 3 (17%) cases, tumor-infiltrating lymphocytes expressed PD-L1 in the majority of the cases analyzed and in all of the cases positive for tumor cell PD-L1.6
Another study evaluated PD-1 and PD-L1 expression in EMPD tumor cells and tumor-associated immune infiltrate.5 They found that PD-1 was expressed heavily by the tumor-associated immune infiltrate in all EMPD cases analyzed. Similar to the previously mentioned study,6 PD-L1 was expressed by tumor cells in a few cases only. Interestingly, they found that the density of CD3 in the tumor-associated immune infiltrate was significantly (P=.049) higher in patients who were alive than in those who died, suggesting the importance of an exuberant T-cell response for survival in EMPD.5
A third study investigated protein expression of the B7 family members as well as PD-1 and PD-L1/2 in 55 EMPD samples. In this study the authors also found that tumor cell PD-L1 was minimal. Interestingly, they also found that tumor cells expressed B7 proteins in the majority of the cases.7
Finally, another study examined activity levels of T cells in EMPD by measuring the number and expression levels of cytotoxic T-cell cytokines.24 The authors first found that EMPD tumors had a significantly higher number of CD8+ tumor-infiltrating lymphocytes compared to peripheral blood (P<.01). These CD8+ tumor-infiltrating lymphocytes also had a significantly higher expression of PD-1 (P<.01). They also found that tumor cells produced an immunosuppressive molecule called indoleamine 2,3-dyoxygenae that functions by suppressing T-cell activity levels. They concluded that in EMPD, tumor-specific T lymphocytes have an exhausted phenotype due to PD-1 activation as well as indoleamine 2,3-dyoxygenase release to the tumor microenvironment.24
These studies highlight that restoring the effector functions of tumor-specific T lymphocytes could be an effective treatment strategy for EMPD. In fact, immunotherapy has been used with success for EMPD in the form of topical immunomodulators such as imiquimod.16,25 More than 40 cases of EMPD treated with imiquimod 5% have been published; of these, only 6 were considered nonresponders,5 which suggests that EMPD may respond to other immunotherapies such as checkpoint inhibitors. It is an exciting time for immunotherapy as more checkpoint inhibitors are being developed. Among the newer agents is cemiplimab, which is a PD-1 inhibitor now US Food and Drug Administration approved for the treatment of locally advanced or metastatic cutaneous squamous cell carcinoma in patients who are not candidates for curative surgery or curative radiation.26 Programmed cell death receptor 1 signaling can serve as a potential target in EMPD, and further studies need to be performed to test the clinical efficacy, especially in unresectable or invasive/metastatic EMPD. As the PD-1 pathway is more studied in EMPD, and as more PD-1 inhibitors get developed, it would be a clinical need to establish clinical studies for PD-1 inhibitors in EMPD.
- Ito T, Kaku-Ito Y, Furue M. The diagnosis and management of extramammary Paget’s disease. Expert Rev Anticancer Ther. 2018;18:543-553.
- van der Zwan JM, Siesling S, Blokx WAM, et al. Invasive extramammary Paget’s disease and the risk for secondary tumours in Europe. Eur J Surg Oncol. 2012;38:214-221.
- Simonds RM, Segal RJ, Sharma A. Extramammary Paget’s disease: a review of the literature. Int J Dermatol. 2019;58:871-879.
- Wollina U, Goldman A, Bieneck A, et al. Surgical treatment for extramammary Paget’s disease. Curr Treat Options Oncol. 2018;19:27.
- Mauzo SH, Tetzlaff MT, Milton DR, et al. Expression of PD-1 and PD-L1 in extramammary Paget disease: implications for immune-targeted therapy. Cancers (Basel). 2019;11:754.
- Fowler MR, Flanigan KL, Googe PB. PD-L1 expression in extramammary Paget disease [published online March 6, 2020]. Am J Dermatopathol. doi:10.1097/dad.0000000000001622.
- Pourmaleki M, Young JH, Socci ND, et al. Extramammary Paget disease shows differential expression of B7 family members B7-H3, B7-H4, PD-L1, PD-L2 and cancer/testis antigens NY-ESO-1 and MAGE-A. Oncotarget. 2019;10:6152-6167.
- Mahoney KM, Freeman GJ, McDermott DF. The next immune-checkpoint inhibitors: PD-1/PD-L1 blockade in melanoma. Clin Ther. 2015;37:764-782.
- Dany M, Nganga R, Chidiac A, et al. Advances in immunotherapy for melanoma management. Hum Vaccines Immunother. 2016;12:2501-2511.
- Richter MD, Hughes GC, Chung SH, et al. Immunologic adverse events from immune checkpoint therapy [published online April 13, 2020]. Best Pract Res Clin Rheumatol. doi:10.1016/j.berh.2020.101511.
- Kang Z, Zhang Q, Zhang Q, et al. Clinical and pathological characteristics of extramammary Paget’s disease: report of 246 Chinese male patients. Int J Clin Exp Pathol. 2015;8:13233-13240.
- Ohara K, Fujisawa Y, Yoshino K, et al. A proposal for a TNM staging system for extramammary Paget disease: retrospective analysis of 301 patients with invasive primary tumors. J Dermatol Sci. 2016;83:234-239.
- Hatta N. Prognostic factors of extramammary Paget’s disease. Curr Treat Options Oncol. 2018;19:47.
- Yao H, Xie M, Fu S, et al. Survival analysis of patients with invasive extramammary Paget disease: implications of anatomic sites. BMC Cancer. 2018;18:403.
- Herrel LA, Weiss AD, Goodman M, et al. Extramammary Paget’s disease in males: survival outcomes in 495 patients. Ann Surg Oncol. 2015;22:1625-1630.
- Sanderson P, Innamaa A, Palmer J, et al. Imiquimod therapy for extramammary Paget’s disease of the vulva: a viable non-surgical alternative. J Obstet Gynaecol. 2013;33:479-483.
- Smith AA. Pre-Paget cells: evidence of keratinocyte origin of extramammary Paget’s disease. Intractable Rare Dis Res. 2019;8:203-205.
- Garganese G, Inzani F, Mantovani G, et al. The vulvar immunohistochemical panel (VIP) project: molecular profiles of vulvar Paget’s disease. J Cancer Res Clin Oncol. 2019;145:2211-2225.
- Dias-Santagata D, Lam Q, Bergethon K, et al. A potential role for targeted therapy in a subset of metastasizing adnexal carcinomas. Mod Pathol. 2011;24:974-982.
- Cohen JM, Granter SR, Werchniak AE. Risk stratification in extramammary Paget disease. Clin Exp Dermatol. 2015;40:473-478.
- Wei SC, Duffy CR, Allison JP. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 2018;8:1069-1086.
- Shi Y. Regulatory mechanisms of PD-L1 expression in cancer cells. Cancer Immunol Immunother. 2018;67:1481-1489.
- Cui C, Yu B, Jiang Q, et al. The roles of PD-1/PD-L1 and its signalling pathway in gastrointestinal tract cancers. Clin Exp Pharmacol Physiol. 2019;46:3-10.
- Iga N, Otsuka A, Yamamoto Y, et al. Accumulation of exhausted CD8+ T cells in extramammary Paget’s disease. PLoS One. 2019;14:E0211135.
- Frances L, Pascual JC, Leiva-Salinas M, et al. Extramammary Paget disease successfully treated with topical imiquimod 5% and tazarotene. Dermatol Ther. 2014;27:19-20.
- Lee A, Duggan S, Deeks ED. Cemiplimab: a review in advanced cutaneous squamous cell carcinoma. Drugs. 2020;80:813-819.
Primary extramammary Paget disease (EMPD) is an adnexal carcinoma of the apocrine gland ducts that presents as an erythematous patch on cutaneous sites rich with apocrine glands.1 Primary EMPD can be in situ or invasive with the potential to become metastatic.2 Treatment of primary EMPD is challenging due to the difficulty of achieving clear surgical margins, as the tumor has microscopic spread throughout the epidermis in a skipping fashion.3 Mohs micrographic surgery is the treatment of choice; however, there is a clinical need to identify additional treatment modalities, especially for patients with unresectable, invasive, or metastatic primary EMPD,4 which partly is due to lack of data to understand the pathogenesis of primary EMPD. Recently, there have been studies investigating the genetic characteristics of EMPD tumors. The interaction between the programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) is one of the pathways recently studied and has been reported to be a potential target in EMPD.5-7 Programmed cell death receptor 1 signaling constitutes an immune checkpoint pathway that regulates the activation of tumor-specific T cells.8 In several malignancies, cancer cells express PD-L1 on their surface to activate PD-1 signaling in T cells as a mechanism to dampen the tumor-specific immune response and evade antitumor immunity.9 Thus, blocking PD-1 signaling widely is used to activate tumor-specific T cells and decrease tumor burden.10 Given the advances of immunotherapy in many neoplasms and the paucity of effective agents to treat EMPD, this article serves to shed light on recent data studying PD-1 signaling in EMPD and highlights the potential clinical use of immunotherapy for EMPD.
EMPD and Its Subtypes
Extramammary Paget disease is a rare adenocarcinoma typically affecting older patients (age >60 years) in cutaneous sites with abundant apocrine glands such as the genital and perianal skin.3 Extramammary Paget disease presents as an erythematous patch and frequently is treated initially as a skin dermatosis, resulting in a delay in diagnosis. Histologically, EMPD is characterized by the presence of single cells or a nest of cells having abundant pale cytoplasm and large vesicular nuclei distributed in the epidermis in a pagetoid fashion.11
Extramammary Paget disease can be primary or secondary; the 2 subtypes behave differently both clinically and prognostically. Although primary EMPD is considered to be an adnexal carcinoma of the apocrine gland ducts, secondary EMPD is considered to be an intraepithelial extension of malignant cells from an underlying internal neoplasm.12 The underlying malignancies usually are located within dermal adnexal glands or organs in the vicinity of the cutaneous lesion, such as the colon in the case of perianal EMPD. Histologically, primary and secondary EMPD can be differentiated based on their immunophenotypic staining profiles. Although all cases of EMPD show positive immunohistochemistry staining for cytokeratin 7, carcinoembryonic antigen, and epithelial membrane antigen, only primary EMPD will additionally stain for GCDFP-15 (gross cystic disease fluid protein 15) and GATA.11 Regardless of the immunohistochemistry stains, every patient newly diagnosed with EMPD deserves a full workup for malignancy screening, including a colonoscopy, cystoscopy, mammography and Papanicolaou test in women, pelvic ultrasound, and computed tomography of the abdomen and pelvis.13
The first-line treatment of EMPD is surgery; however, obtaining clear surgical margins can be a challenge, with high recurrence rates due to the microscopic spread of the disease throughout the epidermis.4 In addition, anatomic location affects the surgical approach and patient survival. Recent studies on EMPD mortality outcomes in women show that mortality is higher in patients with vaginal EMPD than in those with vulvar/labial EMPD, partly due to the sensitive location that makes it difficult to perform wide local excisions.13,14 Assessing the entire margins with tissue preservation using Mohs micrographic surgery has been shown to be successful in decreasing the recurrence rate, especially when coupled with the use of cytokeratin 7 immunohistochemistry.4 Other treatment modalities include radiation, topical imiquimod, and photodynamic therapy.15,16 Regardless of treatment modality, EMPD requires long‐term follow-up to monitor for disease recurrence, regional lymphadenopathy, distant metastasis, or development of an internal malignancy.
The pathogenesis of primary EMPD remains unclear. The tumor is thought to be derived from Toker cells, which are pluripotent adnexal stem cells located in the epidermis that normally give rise to apocrine glands.17 There have been few studies investigating the genetic characteristics of EMPD lesions in an attempt to understand pathogenesis as well as to find druggable targets. Current data for targeted therapy have focused on HER2 (human epidermal growth factor receptor 2) hormone receptor expression,18 ERBB (erythroblastic oncogene B) amplification,19 CDK4 (cyclin-dependent kinase 4)–cyclin D1 signaling,20 and most recently PD-1/PD-L1 pathway.5-7
PD-1 Expression in EMPD: Implication for Immunotherapy
Most tumors display novel antigens that are recognized by the host immune system and thus stimulate cell-mediated and humoral pathways. The immune system naturally provides regulatory immune checkpoints to T cell–mediated immune responses. One of these checkpoints involves the interaction between PD-1 on T cells and its ligand PD-L1 on tumor cells.21 When PD-1 binds to PD-L1 on tumor cells, there is inhibition of T-cell proliferation, a decrease in cytokine production, and induction of T-cell cytolysis.22 The Figure summarizes the dynamics for T-cell regulation.
Naturally, tumor-infiltrating T cells trigger their own inhibition by binding to PD-L1. However, certain tumor cells constitutively upregulate the expression of PD-L1. With that, the tumor cells gain the ability to suppress T cells and avoid T cell–mediated cytotoxicity,23 which is known as the adoptive immune resistance mechanism. There have been several studies in the literature investigating the PD-1 signaling pathway in EMPD as a way to determine if EMPD would be susceptible to immune checkpoint blockade. The success of checkpoint inhibitor immunotherapy generally correlates with increased PD-L1 expression by tumor cells.
One study evaluated the expression of PD-L1 in tumor cells and tumor-infiltrating T cells in 18 cases of EMPD.6 The authors identified that even though tumor cell PD-L1 expression was detected in only 3 (17%) cases, tumor-infiltrating lymphocytes expressed PD-L1 in the majority of the cases analyzed and in all of the cases positive for tumor cell PD-L1.6
Another study evaluated PD-1 and PD-L1 expression in EMPD tumor cells and tumor-associated immune infiltrate.5 They found that PD-1 was expressed heavily by the tumor-associated immune infiltrate in all EMPD cases analyzed. Similar to the previously mentioned study,6 PD-L1 was expressed by tumor cells in a few cases only. Interestingly, they found that the density of CD3 in the tumor-associated immune infiltrate was significantly (P=.049) higher in patients who were alive than in those who died, suggesting the importance of an exuberant T-cell response for survival in EMPD.5
A third study investigated protein expression of the B7 family members as well as PD-1 and PD-L1/2 in 55 EMPD samples. In this study the authors also found that tumor cell PD-L1 was minimal. Interestingly, they also found that tumor cells expressed B7 proteins in the majority of the cases.7
Finally, another study examined activity levels of T cells in EMPD by measuring the number and expression levels of cytotoxic T-cell cytokines.24 The authors first found that EMPD tumors had a significantly higher number of CD8+ tumor-infiltrating lymphocytes compared to peripheral blood (P<.01). These CD8+ tumor-infiltrating lymphocytes also had a significantly higher expression of PD-1 (P<.01). They also found that tumor cells produced an immunosuppressive molecule called indoleamine 2,3-dyoxygenae that functions by suppressing T-cell activity levels. They concluded that in EMPD, tumor-specific T lymphocytes have an exhausted phenotype due to PD-1 activation as well as indoleamine 2,3-dyoxygenase release to the tumor microenvironment.24
These studies highlight that restoring the effector functions of tumor-specific T lymphocytes could be an effective treatment strategy for EMPD. In fact, immunotherapy has been used with success for EMPD in the form of topical immunomodulators such as imiquimod.16,25 More than 40 cases of EMPD treated with imiquimod 5% have been published; of these, only 6 were considered nonresponders,5 which suggests that EMPD may respond to other immunotherapies such as checkpoint inhibitors. It is an exciting time for immunotherapy as more checkpoint inhibitors are being developed. Among the newer agents is cemiplimab, which is a PD-1 inhibitor now US Food and Drug Administration approved for the treatment of locally advanced or metastatic cutaneous squamous cell carcinoma in patients who are not candidates for curative surgery or curative radiation.26 Programmed cell death receptor 1 signaling can serve as a potential target in EMPD, and further studies need to be performed to test the clinical efficacy, especially in unresectable or invasive/metastatic EMPD. As the PD-1 pathway is more studied in EMPD, and as more PD-1 inhibitors get developed, it would be a clinical need to establish clinical studies for PD-1 inhibitors in EMPD.
Primary extramammary Paget disease (EMPD) is an adnexal carcinoma of the apocrine gland ducts that presents as an erythematous patch on cutaneous sites rich with apocrine glands.1 Primary EMPD can be in situ or invasive with the potential to become metastatic.2 Treatment of primary EMPD is challenging due to the difficulty of achieving clear surgical margins, as the tumor has microscopic spread throughout the epidermis in a skipping fashion.3 Mohs micrographic surgery is the treatment of choice; however, there is a clinical need to identify additional treatment modalities, especially for patients with unresectable, invasive, or metastatic primary EMPD,4 which partly is due to lack of data to understand the pathogenesis of primary EMPD. Recently, there have been studies investigating the genetic characteristics of EMPD tumors. The interaction between the programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) is one of the pathways recently studied and has been reported to be a potential target in EMPD.5-7 Programmed cell death receptor 1 signaling constitutes an immune checkpoint pathway that regulates the activation of tumor-specific T cells.8 In several malignancies, cancer cells express PD-L1 on their surface to activate PD-1 signaling in T cells as a mechanism to dampen the tumor-specific immune response and evade antitumor immunity.9 Thus, blocking PD-1 signaling widely is used to activate tumor-specific T cells and decrease tumor burden.10 Given the advances of immunotherapy in many neoplasms and the paucity of effective agents to treat EMPD, this article serves to shed light on recent data studying PD-1 signaling in EMPD and highlights the potential clinical use of immunotherapy for EMPD.
EMPD and Its Subtypes
Extramammary Paget disease is a rare adenocarcinoma typically affecting older patients (age >60 years) in cutaneous sites with abundant apocrine glands such as the genital and perianal skin.3 Extramammary Paget disease presents as an erythematous patch and frequently is treated initially as a skin dermatosis, resulting in a delay in diagnosis. Histologically, EMPD is characterized by the presence of single cells or a nest of cells having abundant pale cytoplasm and large vesicular nuclei distributed in the epidermis in a pagetoid fashion.11
Extramammary Paget disease can be primary or secondary; the 2 subtypes behave differently both clinically and prognostically. Although primary EMPD is considered to be an adnexal carcinoma of the apocrine gland ducts, secondary EMPD is considered to be an intraepithelial extension of malignant cells from an underlying internal neoplasm.12 The underlying malignancies usually are located within dermal adnexal glands or organs in the vicinity of the cutaneous lesion, such as the colon in the case of perianal EMPD. Histologically, primary and secondary EMPD can be differentiated based on their immunophenotypic staining profiles. Although all cases of EMPD show positive immunohistochemistry staining for cytokeratin 7, carcinoembryonic antigen, and epithelial membrane antigen, only primary EMPD will additionally stain for GCDFP-15 (gross cystic disease fluid protein 15) and GATA.11 Regardless of the immunohistochemistry stains, every patient newly diagnosed with EMPD deserves a full workup for malignancy screening, including a colonoscopy, cystoscopy, mammography and Papanicolaou test in women, pelvic ultrasound, and computed tomography of the abdomen and pelvis.13
The first-line treatment of EMPD is surgery; however, obtaining clear surgical margins can be a challenge, with high recurrence rates due to the microscopic spread of the disease throughout the epidermis.4 In addition, anatomic location affects the surgical approach and patient survival. Recent studies on EMPD mortality outcomes in women show that mortality is higher in patients with vaginal EMPD than in those with vulvar/labial EMPD, partly due to the sensitive location that makes it difficult to perform wide local excisions.13,14 Assessing the entire margins with tissue preservation using Mohs micrographic surgery has been shown to be successful in decreasing the recurrence rate, especially when coupled with the use of cytokeratin 7 immunohistochemistry.4 Other treatment modalities include radiation, topical imiquimod, and photodynamic therapy.15,16 Regardless of treatment modality, EMPD requires long‐term follow-up to monitor for disease recurrence, regional lymphadenopathy, distant metastasis, or development of an internal malignancy.
The pathogenesis of primary EMPD remains unclear. The tumor is thought to be derived from Toker cells, which are pluripotent adnexal stem cells located in the epidermis that normally give rise to apocrine glands.17 There have been few studies investigating the genetic characteristics of EMPD lesions in an attempt to understand pathogenesis as well as to find druggable targets. Current data for targeted therapy have focused on HER2 (human epidermal growth factor receptor 2) hormone receptor expression,18 ERBB (erythroblastic oncogene B) amplification,19 CDK4 (cyclin-dependent kinase 4)–cyclin D1 signaling,20 and most recently PD-1/PD-L1 pathway.5-7
PD-1 Expression in EMPD: Implication for Immunotherapy
Most tumors display novel antigens that are recognized by the host immune system and thus stimulate cell-mediated and humoral pathways. The immune system naturally provides regulatory immune checkpoints to T cell–mediated immune responses. One of these checkpoints involves the interaction between PD-1 on T cells and its ligand PD-L1 on tumor cells.21 When PD-1 binds to PD-L1 on tumor cells, there is inhibition of T-cell proliferation, a decrease in cytokine production, and induction of T-cell cytolysis.22 The Figure summarizes the dynamics for T-cell regulation.
Naturally, tumor-infiltrating T cells trigger their own inhibition by binding to PD-L1. However, certain tumor cells constitutively upregulate the expression of PD-L1. With that, the tumor cells gain the ability to suppress T cells and avoid T cell–mediated cytotoxicity,23 which is known as the adoptive immune resistance mechanism. There have been several studies in the literature investigating the PD-1 signaling pathway in EMPD as a way to determine if EMPD would be susceptible to immune checkpoint blockade. The success of checkpoint inhibitor immunotherapy generally correlates with increased PD-L1 expression by tumor cells.
One study evaluated the expression of PD-L1 in tumor cells and tumor-infiltrating T cells in 18 cases of EMPD.6 The authors identified that even though tumor cell PD-L1 expression was detected in only 3 (17%) cases, tumor-infiltrating lymphocytes expressed PD-L1 in the majority of the cases analyzed and in all of the cases positive for tumor cell PD-L1.6
Another study evaluated PD-1 and PD-L1 expression in EMPD tumor cells and tumor-associated immune infiltrate.5 They found that PD-1 was expressed heavily by the tumor-associated immune infiltrate in all EMPD cases analyzed. Similar to the previously mentioned study,6 PD-L1 was expressed by tumor cells in a few cases only. Interestingly, they found that the density of CD3 in the tumor-associated immune infiltrate was significantly (P=.049) higher in patients who were alive than in those who died, suggesting the importance of an exuberant T-cell response for survival in EMPD.5
A third study investigated protein expression of the B7 family members as well as PD-1 and PD-L1/2 in 55 EMPD samples. In this study the authors also found that tumor cell PD-L1 was minimal. Interestingly, they also found that tumor cells expressed B7 proteins in the majority of the cases.7
Finally, another study examined activity levels of T cells in EMPD by measuring the number and expression levels of cytotoxic T-cell cytokines.24 The authors first found that EMPD tumors had a significantly higher number of CD8+ tumor-infiltrating lymphocytes compared to peripheral blood (P<.01). These CD8+ tumor-infiltrating lymphocytes also had a significantly higher expression of PD-1 (P<.01). They also found that tumor cells produced an immunosuppressive molecule called indoleamine 2,3-dyoxygenae that functions by suppressing T-cell activity levels. They concluded that in EMPD, tumor-specific T lymphocytes have an exhausted phenotype due to PD-1 activation as well as indoleamine 2,3-dyoxygenase release to the tumor microenvironment.24
These studies highlight that restoring the effector functions of tumor-specific T lymphocytes could be an effective treatment strategy for EMPD. In fact, immunotherapy has been used with success for EMPD in the form of topical immunomodulators such as imiquimod.16,25 More than 40 cases of EMPD treated with imiquimod 5% have been published; of these, only 6 were considered nonresponders,5 which suggests that EMPD may respond to other immunotherapies such as checkpoint inhibitors. It is an exciting time for immunotherapy as more checkpoint inhibitors are being developed. Among the newer agents is cemiplimab, which is a PD-1 inhibitor now US Food and Drug Administration approved for the treatment of locally advanced or metastatic cutaneous squamous cell carcinoma in patients who are not candidates for curative surgery or curative radiation.26 Programmed cell death receptor 1 signaling can serve as a potential target in EMPD, and further studies need to be performed to test the clinical efficacy, especially in unresectable or invasive/metastatic EMPD. As the PD-1 pathway is more studied in EMPD, and as more PD-1 inhibitors get developed, it would be a clinical need to establish clinical studies for PD-1 inhibitors in EMPD.
- Ito T, Kaku-Ito Y, Furue M. The diagnosis and management of extramammary Paget’s disease. Expert Rev Anticancer Ther. 2018;18:543-553.
- van der Zwan JM, Siesling S, Blokx WAM, et al. Invasive extramammary Paget’s disease and the risk for secondary tumours in Europe. Eur J Surg Oncol. 2012;38:214-221.
- Simonds RM, Segal RJ, Sharma A. Extramammary Paget’s disease: a review of the literature. Int J Dermatol. 2019;58:871-879.
- Wollina U, Goldman A, Bieneck A, et al. Surgical treatment for extramammary Paget’s disease. Curr Treat Options Oncol. 2018;19:27.
- Mauzo SH, Tetzlaff MT, Milton DR, et al. Expression of PD-1 and PD-L1 in extramammary Paget disease: implications for immune-targeted therapy. Cancers (Basel). 2019;11:754.
- Fowler MR, Flanigan KL, Googe PB. PD-L1 expression in extramammary Paget disease [published online March 6, 2020]. Am J Dermatopathol. doi:10.1097/dad.0000000000001622.
- Pourmaleki M, Young JH, Socci ND, et al. Extramammary Paget disease shows differential expression of B7 family members B7-H3, B7-H4, PD-L1, PD-L2 and cancer/testis antigens NY-ESO-1 and MAGE-A. Oncotarget. 2019;10:6152-6167.
- Mahoney KM, Freeman GJ, McDermott DF. The next immune-checkpoint inhibitors: PD-1/PD-L1 blockade in melanoma. Clin Ther. 2015;37:764-782.
- Dany M, Nganga R, Chidiac A, et al. Advances in immunotherapy for melanoma management. Hum Vaccines Immunother. 2016;12:2501-2511.
- Richter MD, Hughes GC, Chung SH, et al. Immunologic adverse events from immune checkpoint therapy [published online April 13, 2020]. Best Pract Res Clin Rheumatol. doi:10.1016/j.berh.2020.101511.
- Kang Z, Zhang Q, Zhang Q, et al. Clinical and pathological characteristics of extramammary Paget’s disease: report of 246 Chinese male patients. Int J Clin Exp Pathol. 2015;8:13233-13240.
- Ohara K, Fujisawa Y, Yoshino K, et al. A proposal for a TNM staging system for extramammary Paget disease: retrospective analysis of 301 patients with invasive primary tumors. J Dermatol Sci. 2016;83:234-239.
- Hatta N. Prognostic factors of extramammary Paget’s disease. Curr Treat Options Oncol. 2018;19:47.
- Yao H, Xie M, Fu S, et al. Survival analysis of patients with invasive extramammary Paget disease: implications of anatomic sites. BMC Cancer. 2018;18:403.
- Herrel LA, Weiss AD, Goodman M, et al. Extramammary Paget’s disease in males: survival outcomes in 495 patients. Ann Surg Oncol. 2015;22:1625-1630.
- Sanderson P, Innamaa A, Palmer J, et al. Imiquimod therapy for extramammary Paget’s disease of the vulva: a viable non-surgical alternative. J Obstet Gynaecol. 2013;33:479-483.
- Smith AA. Pre-Paget cells: evidence of keratinocyte origin of extramammary Paget’s disease. Intractable Rare Dis Res. 2019;8:203-205.
- Garganese G, Inzani F, Mantovani G, et al. The vulvar immunohistochemical panel (VIP) project: molecular profiles of vulvar Paget’s disease. J Cancer Res Clin Oncol. 2019;145:2211-2225.
- Dias-Santagata D, Lam Q, Bergethon K, et al. A potential role for targeted therapy in a subset of metastasizing adnexal carcinomas. Mod Pathol. 2011;24:974-982.
- Cohen JM, Granter SR, Werchniak AE. Risk stratification in extramammary Paget disease. Clin Exp Dermatol. 2015;40:473-478.
- Wei SC, Duffy CR, Allison JP. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 2018;8:1069-1086.
- Shi Y. Regulatory mechanisms of PD-L1 expression in cancer cells. Cancer Immunol Immunother. 2018;67:1481-1489.
- Cui C, Yu B, Jiang Q, et al. The roles of PD-1/PD-L1 and its signalling pathway in gastrointestinal tract cancers. Clin Exp Pharmacol Physiol. 2019;46:3-10.
- Iga N, Otsuka A, Yamamoto Y, et al. Accumulation of exhausted CD8+ T cells in extramammary Paget’s disease. PLoS One. 2019;14:E0211135.
- Frances L, Pascual JC, Leiva-Salinas M, et al. Extramammary Paget disease successfully treated with topical imiquimod 5% and tazarotene. Dermatol Ther. 2014;27:19-20.
- Lee A, Duggan S, Deeks ED. Cemiplimab: a review in advanced cutaneous squamous cell carcinoma. Drugs. 2020;80:813-819.
- Ito T, Kaku-Ito Y, Furue M. The diagnosis and management of extramammary Paget’s disease. Expert Rev Anticancer Ther. 2018;18:543-553.
- van der Zwan JM, Siesling S, Blokx WAM, et al. Invasive extramammary Paget’s disease and the risk for secondary tumours in Europe. Eur J Surg Oncol. 2012;38:214-221.
- Simonds RM, Segal RJ, Sharma A. Extramammary Paget’s disease: a review of the literature. Int J Dermatol. 2019;58:871-879.
- Wollina U, Goldman A, Bieneck A, et al. Surgical treatment for extramammary Paget’s disease. Curr Treat Options Oncol. 2018;19:27.
- Mauzo SH, Tetzlaff MT, Milton DR, et al. Expression of PD-1 and PD-L1 in extramammary Paget disease: implications for immune-targeted therapy. Cancers (Basel). 2019;11:754.
- Fowler MR, Flanigan KL, Googe PB. PD-L1 expression in extramammary Paget disease [published online March 6, 2020]. Am J Dermatopathol. doi:10.1097/dad.0000000000001622.
- Pourmaleki M, Young JH, Socci ND, et al. Extramammary Paget disease shows differential expression of B7 family members B7-H3, B7-H4, PD-L1, PD-L2 and cancer/testis antigens NY-ESO-1 and MAGE-A. Oncotarget. 2019;10:6152-6167.
- Mahoney KM, Freeman GJ, McDermott DF. The next immune-checkpoint inhibitors: PD-1/PD-L1 blockade in melanoma. Clin Ther. 2015;37:764-782.
- Dany M, Nganga R, Chidiac A, et al. Advances in immunotherapy for melanoma management. Hum Vaccines Immunother. 2016;12:2501-2511.
- Richter MD, Hughes GC, Chung SH, et al. Immunologic adverse events from immune checkpoint therapy [published online April 13, 2020]. Best Pract Res Clin Rheumatol. doi:10.1016/j.berh.2020.101511.
- Kang Z, Zhang Q, Zhang Q, et al. Clinical and pathological characteristics of extramammary Paget’s disease: report of 246 Chinese male patients. Int J Clin Exp Pathol. 2015;8:13233-13240.
- Ohara K, Fujisawa Y, Yoshino K, et al. A proposal for a TNM staging system for extramammary Paget disease: retrospective analysis of 301 patients with invasive primary tumors. J Dermatol Sci. 2016;83:234-239.
- Hatta N. Prognostic factors of extramammary Paget’s disease. Curr Treat Options Oncol. 2018;19:47.
- Yao H, Xie M, Fu S, et al. Survival analysis of patients with invasive extramammary Paget disease: implications of anatomic sites. BMC Cancer. 2018;18:403.
- Herrel LA, Weiss AD, Goodman M, et al. Extramammary Paget’s disease in males: survival outcomes in 495 patients. Ann Surg Oncol. 2015;22:1625-1630.
- Sanderson P, Innamaa A, Palmer J, et al. Imiquimod therapy for extramammary Paget’s disease of the vulva: a viable non-surgical alternative. J Obstet Gynaecol. 2013;33:479-483.
- Smith AA. Pre-Paget cells: evidence of keratinocyte origin of extramammary Paget’s disease. Intractable Rare Dis Res. 2019;8:203-205.
- Garganese G, Inzani F, Mantovani G, et al. The vulvar immunohistochemical panel (VIP) project: molecular profiles of vulvar Paget’s disease. J Cancer Res Clin Oncol. 2019;145:2211-2225.
- Dias-Santagata D, Lam Q, Bergethon K, et al. A potential role for targeted therapy in a subset of metastasizing adnexal carcinomas. Mod Pathol. 2011;24:974-982.
- Cohen JM, Granter SR, Werchniak AE. Risk stratification in extramammary Paget disease. Clin Exp Dermatol. 2015;40:473-478.
- Wei SC, Duffy CR, Allison JP. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 2018;8:1069-1086.
- Shi Y. Regulatory mechanisms of PD-L1 expression in cancer cells. Cancer Immunol Immunother. 2018;67:1481-1489.
- Cui C, Yu B, Jiang Q, et al. The roles of PD-1/PD-L1 and its signalling pathway in gastrointestinal tract cancers. Clin Exp Pharmacol Physiol. 2019;46:3-10.
- Iga N, Otsuka A, Yamamoto Y, et al. Accumulation of exhausted CD8+ T cells in extramammary Paget’s disease. PLoS One. 2019;14:E0211135.
- Frances L, Pascual JC, Leiva-Salinas M, et al. Extramammary Paget disease successfully treated with topical imiquimod 5% and tazarotene. Dermatol Ther. 2014;27:19-20.
- Lee A, Duggan S, Deeks ED. Cemiplimab: a review in advanced cutaneous squamous cell carcinoma. Drugs. 2020;80:813-819.
Resident Pearls
- Primary extramammary Paget disease (EMPD) is an adnexal carcinoma of the apocrine gland ducts, while secondary EMPD is an extension of malignant cells from an underlying internal neoplasm.
- Surgical margin clearance in EMPD often is problematic, with high recurrence rates indicating the need for additional treatment modalities.
- Programmed cell death receptor 1 (PD-1) signaling can serve as a potential target in EMPD. Further studies and clinical trials are needed to test the efficacy of PD-1 inhibitors in unresectable or invasive/metastatic EMPD.
