When I was an intern and junior resident there was a fellow house officer who seemed to be a magnet for out-of-hospital emergencies. There were a couple of car accidents, a baby to be delivered, an elderly neighbor with alarming chest pain, and a little old lady with syncope, plus a few playground incidents that required more than a little on-site tending and triage. It got to the point where he felt he needed to raid the hospital supply closets to build himself a proper emergency kit.

Envious of his excitement I, of course, followed suit. However, my well-appointed plastic tackle box remained unopened on the floor behind the driver’s seat in my car. Sure, there were Band-Aids to be dispensed from time to time but mostly I was the on-site reassurer and triage consultant at the playground. I almost never suggested a trip to the emergency room. No little old ladies crumpled to the floor in front of me in the checkout line at the grocery store. No distracted teenage drivers plowed into telephone poles anywhere within earshot.

When I began my practice here on the midcoast of Maine, my protective aura traveled with me. I went looking for excitement by signing on as the team physician for the local high school football team. But, other than a few minor concussions, which in those days we “treated” with a “sit on the bench for awhile and I’ll ask you a few questions,” my first responder experiences continued to be boringly undramatic. Not even any obvious dislocations or angulated fractures on the playground or athletic fields I frequented.

My professional adventures were confined to the hospital, where every physician regardless of specialty training was required to take a shift covering the emergency room. Talk about a situation looking for trouble. The concept of physicians with specialty training in emergency room medicine had not yet occurred to anyone in rural Maine. Although there were anxiety-provoking nights waiting for the disasters to arrive, somehow the shit never hit the fan while I was on duty.

Finally, after several more years of this bad (or good) fortune I was on a bike ride out in the country alone on a back road and came upon a fresh single-vehicle-single-occupant accident. Steam and smoke coming out of the engine compartment, the young driver slumped over the steering wheel. I was able to pry the door open but couldn’t find a pulse. I thumped him three times on the chest and eventually could detect a pulse and he began to stir. When the ambulance arrived I dragged my bike into the back of the ambulance with me and monitored him on the way to the hospital. He did fine, only to die in another accident a few years later.

A recent article in one of our local newspapers described a fledgling program in which three emergency room physicians are being equipped with supplies and communication links that will allow them to respond to emergent situations in the field. The program is currently seeking to extend its funding for another year. Its advocates argue that the need is twofold. There is currently a regional shortage of fully trained first responder EMTs. And having an extra pair of hands in the field could ease the burden of the already overutilized emergency rooms.

I am sure the physicians who have signed on to become first responders are passionate about the need and probably enjoy the excitement of in-the-field professional experiences, much as my fellow house officer did. However, were I sitting on the committee that controls the funding of programs like this I would want to take a step back and consider whether using primary care physicians, who are already in short supply, as first responders made sense. Some of the scenarios may be dramatic and the physician’s contribution may be life saving. But I suspect in the long run these headline-making stories will be few and far between.

The argument that putting physicians in the field will make a significant dent in the emergency room overutilization crisis we have in this country doesn’t hold water. Extending outpatient office hours, education, and improved phone triage to name just a few would have a bigger impact. I suspect there are other countries and even some counties in this country that may already use physicians as first responders. It just doesn’t seem to be a model that will work well given the realities in most semirural and suburban locales.

The real question that must wait for another Letters From Maine column is how well prepared should all of us who have graduated from medical school be to function as first responders. There are thousands of us out there who initially had the training and could, with some updating, become a valuable source of first-responders. Where do issues like continuing education requirements and Good Samaritan protection fit into the equation? The answers in a future Letter.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

When I was an intern and junior resident there was a fellow house officer who seemed to be a magnet for out-of-hospital emergencies. There were a couple of car accidents, a baby to be delivered, an elderly neighbor with alarming chest pain, and a little old lady with syncope, plus a few playground incidents that required more than a little on-site tending and triage. It got to the point where he felt he needed to raid the hospital supply closets to build himself a proper emergency kit.

Envious of his excitement I, of course, followed suit. However, my well-appointed plastic tackle box remained unopened on the floor behind the driver’s seat in my car. Sure, there were Band-Aids to be dispensed from time to time but mostly I was the on-site reassurer and triage consultant at the playground. I almost never suggested a trip to the emergency room. No little old ladies crumpled to the floor in front of me in the checkout line at the grocery store. No distracted teenage drivers plowed into telephone poles anywhere within earshot.

When I began my practice here on the midcoast of Maine, my protective aura traveled with me. I went looking for excitement by signing on as the team physician for the local high school football team. But, other than a few minor concussions, which in those days we “treated” with a “sit on the bench for awhile and I’ll ask you a few questions,” my first responder experiences continued to be boringly undramatic. Not even any obvious dislocations or angulated fractures on the playground or athletic fields I frequented.

My professional adventures were confined to the hospital, where every physician regardless of specialty training was required to take a shift covering the emergency room. Talk about a situation looking for trouble. The concept of physicians with specialty training in emergency room medicine had not yet occurred to anyone in rural Maine. Although there were anxiety-provoking nights waiting for the disasters to arrive, somehow the shit never hit the fan while I was on duty.

Finally, after several more years of this bad (or good) fortune I was on a bike ride out in the country alone on a back road and came upon a fresh single-vehicle-single-occupant accident. Steam and smoke coming out of the engine compartment, the young driver slumped over the steering wheel. I was able to pry the door open but couldn’t find a pulse. I thumped him three times on the chest and eventually could detect a pulse and he began to stir. When the ambulance arrived I dragged my bike into the back of the ambulance with me and monitored him on the way to the hospital. He did fine, only to die in another accident a few years later.

A recent article in one of our local newspapers described a fledgling program in which three emergency room physicians are being equipped with supplies and communication links that will allow them to respond to emergent situations in the field. The program is currently seeking to extend its funding for another year. Its advocates argue that the need is twofold. There is currently a regional shortage of fully trained first responder EMTs. And having an extra pair of hands in the field could ease the burden of the already overutilized emergency rooms.

I am sure the physicians who have signed on to become first responders are passionate about the need and probably enjoy the excitement of in-the-field professional experiences, much as my fellow house officer did. However, were I sitting on the committee that controls the funding of programs like this I would want to take a step back and consider whether using primary care physicians, who are already in short supply, as first responders made sense. Some of the scenarios may be dramatic and the physician’s contribution may be life saving. But I suspect in the long run these headline-making stories will be few and far between.

The argument that putting physicians in the field will make a significant dent in the emergency room overutilization crisis we have in this country doesn’t hold water. Extending outpatient office hours, education, and improved phone triage to name just a few would have a bigger impact. I suspect there are other countries and even some counties in this country that may already use physicians as first responders. It just doesn’t seem to be a model that will work well given the realities in most semirural and suburban locales.

The real question that must wait for another Letters From Maine column is how well prepared should all of us who have graduated from medical school be to function as first responders. There are thousands of us out there who initially had the training and could, with some updating, become a valuable source of first-responders. Where do issues like continuing education requirements and Good Samaritan protection fit into the equation? The answers in a future Letter.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

When I was an intern and junior resident there was a fellow house officer who seemed to be a magnet for out-of-hospital emergencies. There were a couple of car accidents, a baby to be delivered, an elderly neighbor with alarming chest pain, and a little old lady with syncope, plus a few playground incidents that required more than a little on-site tending and triage. It got to the point where he felt he needed to raid the hospital supply closets to build himself a proper emergency kit.

Envious of his excitement I, of course, followed suit. However, my well-appointed plastic tackle box remained unopened on the floor behind the driver’s seat in my car. Sure, there were Band-Aids to be dispensed from time to time but mostly I was the on-site reassurer and triage consultant at the playground. I almost never suggested a trip to the emergency room. No little old ladies crumpled to the floor in front of me in the checkout line at the grocery store. No distracted teenage drivers plowed into telephone poles anywhere within earshot.

When I began my practice here on the midcoast of Maine, my protective aura traveled with me. I went looking for excitement by signing on as the team physician for the local high school football team. But, other than a few minor concussions, which in those days we “treated” with a “sit on the bench for awhile and I’ll ask you a few questions,” my first responder experiences continued to be boringly undramatic. Not even any obvious dislocations or angulated fractures on the playground or athletic fields I frequented.

My professional adventures were confined to the hospital, where every physician regardless of specialty training was required to take a shift covering the emergency room. Talk about a situation looking for trouble. The concept of physicians with specialty training in emergency room medicine had not yet occurred to anyone in rural Maine. Although there were anxiety-provoking nights waiting for the disasters to arrive, somehow the shit never hit the fan while I was on duty.

Finally, after several more years of this bad (or good) fortune I was on a bike ride out in the country alone on a back road and came upon a fresh single-vehicle-single-occupant accident. Steam and smoke coming out of the engine compartment, the young driver slumped over the steering wheel. I was able to pry the door open but couldn’t find a pulse. I thumped him three times on the chest and eventually could detect a pulse and he began to stir. When the ambulance arrived I dragged my bike into the back of the ambulance with me and monitored him on the way to the hospital. He did fine, only to die in another accident a few years later.

A recent article in one of our local newspapers described a fledgling program in which three emergency room physicians are being equipped with supplies and communication links that will allow them to respond to emergent situations in the field. The program is currently seeking to extend its funding for another year. Its advocates argue that the need is twofold. There is currently a regional shortage of fully trained first responder EMTs. And having an extra pair of hands in the field could ease the burden of the already overutilized emergency rooms.

I am sure the physicians who have signed on to become first responders are passionate about the need and probably enjoy the excitement of in-the-field professional experiences, much as my fellow house officer did. However, were I sitting on the committee that controls the funding of programs like this I would want to take a step back and consider whether using primary care physicians, who are already in short supply, as first responders made sense. Some of the scenarios may be dramatic and the physician’s contribution may be life saving. But I suspect in the long run these headline-making stories will be few and far between.

The argument that putting physicians in the field will make a significant dent in the emergency room overutilization crisis we have in this country doesn’t hold water. Extending outpatient office hours, education, and improved phone triage to name just a few would have a bigger impact. I suspect there are other countries and even some counties in this country that may already use physicians as first responders. It just doesn’t seem to be a model that will work well given the realities in most semirural and suburban locales.

The real question that must wait for another Letters From Maine column is how well prepared should all of us who have graduated from medical school be to function as first responders. There are thousands of us out there who initially had the training and could, with some updating, become a valuable source of first-responders. Where do issues like continuing education requirements and Good Samaritan protection fit into the equation? The answers in a future Letter.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

SAN DIEGO — According to data from the American Cancer Society (ACS), cutaneous melanoma was the fifth most common cancer in 2023, with an estimated 97,610 new cases and 7,990 deaths, following cancer of the colorectal area, lung and bronchus, prostate, and breast.

“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist at Skin Care Physicians of Georgia, Macon, said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”

In 2024, the ACS estimates that about 100,640 new melanomas will be diagnosed in the United States (59,170 in men and 41,470 in women), and about 8,290 people are expected to die of melanoma (5,430 men and 2,860 women). Meanwhile, the lifetime risk of melanoma is about 3% (1 in 33) for Whites, 0.1% (1 in 1,000) for Blacks, and 0.5% (1 in 200) for Hispanics. In 2019, there were an estimated 1.4 million people in the United States living with cutaneous melanoma, and the overall 5-year survival is 93.7%.

Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due to sun exposure, changes in recreational behaviors, and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3%-7% per year, “which means that the rate is doubling every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.

While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color, according to a 2023 paper. Black individuals present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.

Risk Factors

Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1 and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.

Dr. Kent said that genetic testing for melanoma is warranted for individuals who meet criteria for the “rule of 3s.” He defined this as three primary melanomas in an individual, or three cases of melanoma in first- or second-degree relatives, or two cases of melanoma and one pancreatic cancer or astrocytoma in first or second-degree relatives, or one case of melanoma and two of pancreatic cancer/astrocytoma in first- or second-degree relatives.

The main environmental risk factor for melanoma is exposure to ultraviolet radiation. Individuals can track their UV exposure with a variety of wearable devices and apps, including SunSense One Digital UV Tracker, the SunSense App, the UV Index Widget, the SunSmart Global UV App, the SunKnown UV light photometer, and the EPA’s UV Index Mobile App. Other environment-related risk factors include having a high socioeconomic status (SES), being immunosuppressed, as well as exposure to heavy metals, insecticides, or hormones; and ones distance from the equator.

In a study published in 2023, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than first melanomas. In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio, 6.36 vs 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03). Second melanomas were also more strongly associated with a history of multiple skin cancer excisions (HR, 2.63 vs 1.86; P = .05).

Dr. Kent noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey in 2014 found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits — even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said at the meeting, which was hosted by the Scripps Cancer Center. “We as dermatologists have work to do to help educate them.”

Dr. Kent reported having no relevant disclosures.

SAN DIEGO — According to data from the American Cancer Society (ACS), cutaneous melanoma was the fifth most common cancer in 2023, with an estimated 97,610 new cases and 7,990 deaths, following cancer of the colorectal area, lung and bronchus, prostate, and breast.

“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist at Skin Care Physicians of Georgia, Macon, said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”

In 2024, the ACS estimates that about 100,640 new melanomas will be diagnosed in the United States (59,170 in men and 41,470 in women), and about 8,290 people are expected to die of melanoma (5,430 men and 2,860 women). Meanwhile, the lifetime risk of melanoma is about 3% (1 in 33) for Whites, 0.1% (1 in 1,000) for Blacks, and 0.5% (1 in 200) for Hispanics. In 2019, there were an estimated 1.4 million people in the United States living with cutaneous melanoma, and the overall 5-year survival is 93.7%.

Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due to sun exposure, changes in recreational behaviors, and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3%-7% per year, “which means that the rate is doubling every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.

While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color, according to a 2023 paper. Black individuals present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.

Risk Factors

Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1 and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.

Dr. Kent said that genetic testing for melanoma is warranted for individuals who meet criteria for the “rule of 3s.” He defined this as three primary melanomas in an individual, or three cases of melanoma in first- or second-degree relatives, or two cases of melanoma and one pancreatic cancer or astrocytoma in first or second-degree relatives, or one case of melanoma and two of pancreatic cancer/astrocytoma in first- or second-degree relatives.

The main environmental risk factor for melanoma is exposure to ultraviolet radiation. Individuals can track their UV exposure with a variety of wearable devices and apps, including SunSense One Digital UV Tracker, the SunSense App, the UV Index Widget, the SunSmart Global UV App, the SunKnown UV light photometer, and the EPA’s UV Index Mobile App. Other environment-related risk factors include having a high socioeconomic status (SES), being immunosuppressed, as well as exposure to heavy metals, insecticides, or hormones; and ones distance from the equator.

In a study published in 2023, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than first melanomas. In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio, 6.36 vs 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03). Second melanomas were also more strongly associated with a history of multiple skin cancer excisions (HR, 2.63 vs 1.86; P = .05).

Dr. Kent noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey in 2014 found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits — even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said at the meeting, which was hosted by the Scripps Cancer Center. “We as dermatologists have work to do to help educate them.”

Dr. Kent reported having no relevant disclosures.

SAN DIEGO — According to data from the American Cancer Society (ACS), cutaneous melanoma was the fifth most common cancer in 2023, with an estimated 97,610 new cases and 7,990 deaths, following cancer of the colorectal area, lung and bronchus, prostate, and breast.

“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist at Skin Care Physicians of Georgia, Macon, said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”

In 2024, the ACS estimates that about 100,640 new melanomas will be diagnosed in the United States (59,170 in men and 41,470 in women), and about 8,290 people are expected to die of melanoma (5,430 men and 2,860 women). Meanwhile, the lifetime risk of melanoma is about 3% (1 in 33) for Whites, 0.1% (1 in 1,000) for Blacks, and 0.5% (1 in 200) for Hispanics. In 2019, there were an estimated 1.4 million people in the United States living with cutaneous melanoma, and the overall 5-year survival is 93.7%.

Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due to sun exposure, changes in recreational behaviors, and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3%-7% per year, “which means that the rate is doubling every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.

While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color, according to a 2023 paper. Black individuals present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.

Risk Factors

Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1 and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.

Dr. Kent said that genetic testing for melanoma is warranted for individuals who meet criteria for the “rule of 3s.” He defined this as three primary melanomas in an individual, or three cases of melanoma in first- or second-degree relatives, or two cases of melanoma and one pancreatic cancer or astrocytoma in first or second-degree relatives, or one case of melanoma and two of pancreatic cancer/astrocytoma in first- or second-degree relatives.

The main environmental risk factor for melanoma is exposure to ultraviolet radiation. Individuals can track their UV exposure with a variety of wearable devices and apps, including SunSense One Digital UV Tracker, the SunSense App, the UV Index Widget, the SunSmart Global UV App, the SunKnown UV light photometer, and the EPA’s UV Index Mobile App. Other environment-related risk factors include having a high socioeconomic status (SES), being immunosuppressed, as well as exposure to heavy metals, insecticides, or hormones; and ones distance from the equator.

In a study published in 2023, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than first melanomas. In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio, 6.36 vs 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03). Second melanomas were also more strongly associated with a history of multiple skin cancer excisions (HR, 2.63 vs 1.86; P = .05).

Dr. Kent noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey in 2014 found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits — even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said at the meeting, which was hosted by the Scripps Cancer Center. “We as dermatologists have work to do to help educate them.”

Dr. Kent reported having no relevant disclosures.

The American Gastroenterological Association (AGA) has published a clinical practice update on polypectomy techniques.

The new guidance document, authored by Andrew P. Copland, MD, of the University of Virginia Health System, Charlottesville, and colleagues, includes 12 pieces of best practice advice pertaining to polyp removal, including the need for evaluation, considerations for selecting a resection strategy, and reasons for referral.

“Polypectomy techniques are continually evolving with improvements in the ability to assess polyps for high-risk features and with development of appropriate procedures for complete and safe polyp resection,” the authors wrote in Clinical Gastroenterology and Hepatology. “This clinical practice update provides guidance in characterizing polyps and choosing appropriate polypectomy techniques for polyps 2 cm or less in size, which comprise most polyps encountered by most endoscopists.”

UVA Health

To begin, they advised a “structured visual assessment using high-definition white light and/or electronic chromoendoscopy and with photodocumentation” for all polyps identified during routine colonoscopy, with close attention to any features suggesting submucosal invasion.

Next, in a series of statements, the guidance document steers appropriate use of various cold and hot polypectomy techniques.

Cold snare polypectomy should be used for polyps less than 10 mm in size, while cold forceps may be considered for polyps 1-3 mm in diameter. Cold resection techniques should also be used for serrated polyps, with use of submucosal injection, if needed, for polyps greater than 10 mm with unclear margins.

For polyps of intermediate size (10-19 mm), both cold and hot snare polypectomy should be considered, alongside endoscopic mucosal resection for polyps, Dr. Copland and colleagues wrote, noting that hot snare polypectomy should be used for removal of pedunculated lesions greater than 10 mm in size.

In contrast, the update advises against use of hot forceps polypectomy in any scenario.

“Hot forceps polypectomy for diminutive and small polyps is associated with higher incomplete polyp removal rates compared with cold snare polypectomy,” the update panelists wrote. “It is also associated with higher risks of postpolypectomy hemorrhage, particularly in the right colon with higher risks of deep thermal injury. Therefore, the use of hot forceps polypectomy is discouraged.”

In another best practice advice statement, the panelists advised against routine use of clips to close resection sites for polyps less than 20 mm. For larger polyps, they advised “selective use” of clips, most suitably in the proximal colon.

Alternatively, patients with polyps at least 20 mm in size should be considered for referral to endoscopic referral centers, along with patients who have polyps in “challenging” locations, and those with a recurrent polyp at a prior polypectomy site.

Patients with nonpedunculated polyps that exhibit “clear evidence of submucosally invasive cancer” should be referred for surgical evaluation, they added. On a similar note, the update advises tattooing lesions that may need to be located at a future surgery or endoscopy.

Finally, Dr. Copland and colleagues advised all endoscopists to understand appropriate selection of electrosurgical generator settings for various polypectomy or postpolypectomy thermal techniques.

“Ongoing research will allow further tailoring of polypectomy techniques to improve patient outcomes,” they concluded.This clinical practice update was commissioned and approved by the AGA Institute. The working group disclosed relationships with Olympus, Boston Scientific, GIE Medical, and others.

The American Gastroenterological Association (AGA) has published a clinical practice update on polypectomy techniques.

The new guidance document, authored by Andrew P. Copland, MD, of the University of Virginia Health System, Charlottesville, and colleagues, includes 12 pieces of best practice advice pertaining to polyp removal, including the need for evaluation, considerations for selecting a resection strategy, and reasons for referral.

“Polypectomy techniques are continually evolving with improvements in the ability to assess polyps for high-risk features and with development of appropriate procedures for complete and safe polyp resection,” the authors wrote in Clinical Gastroenterology and Hepatology. “This clinical practice update provides guidance in characterizing polyps and choosing appropriate polypectomy techniques for polyps 2 cm or less in size, which comprise most polyps encountered by most endoscopists.”

UVA Health

To begin, they advised a “structured visual assessment using high-definition white light and/or electronic chromoendoscopy and with photodocumentation” for all polyps identified during routine colonoscopy, with close attention to any features suggesting submucosal invasion.

Next, in a series of statements, the guidance document steers appropriate use of various cold and hot polypectomy techniques.

Cold snare polypectomy should be used for polyps less than 10 mm in size, while cold forceps may be considered for polyps 1-3 mm in diameter. Cold resection techniques should also be used for serrated polyps, with use of submucosal injection, if needed, for polyps greater than 10 mm with unclear margins.

For polyps of intermediate size (10-19 mm), both cold and hot snare polypectomy should be considered, alongside endoscopic mucosal resection for polyps, Dr. Copland and colleagues wrote, noting that hot snare polypectomy should be used for removal of pedunculated lesions greater than 10 mm in size.

In contrast, the update advises against use of hot forceps polypectomy in any scenario.

“Hot forceps polypectomy for diminutive and small polyps is associated with higher incomplete polyp removal rates compared with cold snare polypectomy,” the update panelists wrote. “It is also associated with higher risks of postpolypectomy hemorrhage, particularly in the right colon with higher risks of deep thermal injury. Therefore, the use of hot forceps polypectomy is discouraged.”

In another best practice advice statement, the panelists advised against routine use of clips to close resection sites for polyps less than 20 mm. For larger polyps, they advised “selective use” of clips, most suitably in the proximal colon.

Alternatively, patients with polyps at least 20 mm in size should be considered for referral to endoscopic referral centers, along with patients who have polyps in “challenging” locations, and those with a recurrent polyp at a prior polypectomy site.

Patients with nonpedunculated polyps that exhibit “clear evidence of submucosally invasive cancer” should be referred for surgical evaluation, they added. On a similar note, the update advises tattooing lesions that may need to be located at a future surgery or endoscopy.

Finally, Dr. Copland and colleagues advised all endoscopists to understand appropriate selection of electrosurgical generator settings for various polypectomy or postpolypectomy thermal techniques.

“Ongoing research will allow further tailoring of polypectomy techniques to improve patient outcomes,” they concluded.This clinical practice update was commissioned and approved by the AGA Institute. The working group disclosed relationships with Olympus, Boston Scientific, GIE Medical, and others.

The American Gastroenterological Association (AGA) has published a clinical practice update on polypectomy techniques.

The new guidance document, authored by Andrew P. Copland, MD, of the University of Virginia Health System, Charlottesville, and colleagues, includes 12 pieces of best practice advice pertaining to polyp removal, including the need for evaluation, considerations for selecting a resection strategy, and reasons for referral.

“Polypectomy techniques are continually evolving with improvements in the ability to assess polyps for high-risk features and with development of appropriate procedures for complete and safe polyp resection,” the authors wrote in Clinical Gastroenterology and Hepatology. “This clinical practice update provides guidance in characterizing polyps and choosing appropriate polypectomy techniques for polyps 2 cm or less in size, which comprise most polyps encountered by most endoscopists.”

UVA Health

To begin, they advised a “structured visual assessment using high-definition white light and/or electronic chromoendoscopy and with photodocumentation” for all polyps identified during routine colonoscopy, with close attention to any features suggesting submucosal invasion.

Next, in a series of statements, the guidance document steers appropriate use of various cold and hot polypectomy techniques.

Cold snare polypectomy should be used for polyps less than 10 mm in size, while cold forceps may be considered for polyps 1-3 mm in diameter. Cold resection techniques should also be used for serrated polyps, with use of submucosal injection, if needed, for polyps greater than 10 mm with unclear margins.

For polyps of intermediate size (10-19 mm), both cold and hot snare polypectomy should be considered, alongside endoscopic mucosal resection for polyps, Dr. Copland and colleagues wrote, noting that hot snare polypectomy should be used for removal of pedunculated lesions greater than 10 mm in size.

In contrast, the update advises against use of hot forceps polypectomy in any scenario.

“Hot forceps polypectomy for diminutive and small polyps is associated with higher incomplete polyp removal rates compared with cold snare polypectomy,” the update panelists wrote. “It is also associated with higher risks of postpolypectomy hemorrhage, particularly in the right colon with higher risks of deep thermal injury. Therefore, the use of hot forceps polypectomy is discouraged.”

In another best practice advice statement, the panelists advised against routine use of clips to close resection sites for polyps less than 20 mm. For larger polyps, they advised “selective use” of clips, most suitably in the proximal colon.

Alternatively, patients with polyps at least 20 mm in size should be considered for referral to endoscopic referral centers, along with patients who have polyps in “challenging” locations, and those with a recurrent polyp at a prior polypectomy site.

Patients with nonpedunculated polyps that exhibit “clear evidence of submucosally invasive cancer” should be referred for surgical evaluation, they added. On a similar note, the update advises tattooing lesions that may need to be located at a future surgery or endoscopy.

Finally, Dr. Copland and colleagues advised all endoscopists to understand appropriate selection of electrosurgical generator settings for various polypectomy or postpolypectomy thermal techniques.

“Ongoing research will allow further tailoring of polypectomy techniques to improve patient outcomes,” they concluded.This clinical practice update was commissioned and approved by the AGA Institute. The working group disclosed relationships with Olympus, Boston Scientific, GIE Medical, and others.

Pathological iron overload with end-organ damage in hemochromatosis occurs in individuals who are homozygous for the major mutation C282Y. Phenotypic hemochromatosis occurs much less frequently in compound heterozygotes with one C282Y mutation and one H63D mutation. Iron overload can be confirmed by magnetic resonance imaging, which shows a loss of signal intensity in affected tissues and avoids the need for liver biopsy.

The serum ferritin level, an acute phase reactant, may be elevated for reasons other than iron overload, including infection and malignancy; in such cases, the iron saturation is usually normal. In patients with liver disease, iron overload is not restricted to patients with genetic hemochromatosis. In nonalcoholic fatty liver disease (NAFLD), up to one-third of patients have an elevated iron saturation (> 45%) and an elevated serum ferritin level. Iron accumulation in NAFLD can occur in hepatocytes, the reticuloendothelial system, or both. Deposition of iron in the reticuloendothelial system has been implicated in more severe liver disease (steatohepatitis and fibrosis) in NAFLD. Hepatic iron accumulation is also frequent in alcohol-associated liver disease. In chronic hepatitis B and C, accumulation of hepatic iron is also recognized.

Dr. Martin is chief of the division of digestive health and liver diseases at the Miller School of Medicine, University of Miami, where he is the Mandel Chair of Gastroenterology. Dr. Friedman is the Anton R. Fried, MD, Chair of the department of medicine at Newton-Wellesley Hospital in Newton, Massachusetts, and assistant chief of medicine at Massachusetts General Hospital, and a professor of medicine at Harvard Medical School and Tufts University School of Medicine, all in Boston. The authors disclosed no conflicts. Previously published in Gastro Hep Advances. 2023 Oct 12. doi: 10.1016/j.gastha.2023.10.004.

Pathological iron overload with end-organ damage in hemochromatosis occurs in individuals who are homozygous for the major mutation C282Y. Phenotypic hemochromatosis occurs much less frequently in compound heterozygotes with one C282Y mutation and one H63D mutation. Iron overload can be confirmed by magnetic resonance imaging, which shows a loss of signal intensity in affected tissues and avoids the need for liver biopsy.

The serum ferritin level, an acute phase reactant, may be elevated for reasons other than iron overload, including infection and malignancy; in such cases, the iron saturation is usually normal. In patients with liver disease, iron overload is not restricted to patients with genetic hemochromatosis. In nonalcoholic fatty liver disease (NAFLD), up to one-third of patients have an elevated iron saturation (> 45%) and an elevated serum ferritin level. Iron accumulation in NAFLD can occur in hepatocytes, the reticuloendothelial system, or both. Deposition of iron in the reticuloendothelial system has been implicated in more severe liver disease (steatohepatitis and fibrosis) in NAFLD. Hepatic iron accumulation is also frequent in alcohol-associated liver disease. In chronic hepatitis B and C, accumulation of hepatic iron is also recognized.

Dr. Martin is chief of the division of digestive health and liver diseases at the Miller School of Medicine, University of Miami, where he is the Mandel Chair of Gastroenterology. Dr. Friedman is the Anton R. Fried, MD, Chair of the department of medicine at Newton-Wellesley Hospital in Newton, Massachusetts, and assistant chief of medicine at Massachusetts General Hospital, and a professor of medicine at Harvard Medical School and Tufts University School of Medicine, all in Boston. The authors disclosed no conflicts. Previously published in Gastro Hep Advances. 2023 Oct 12. doi: 10.1016/j.gastha.2023.10.004.

Pathological iron overload with end-organ damage in hemochromatosis occurs in individuals who are homozygous for the major mutation C282Y. Phenotypic hemochromatosis occurs much less frequently in compound heterozygotes with one C282Y mutation and one H63D mutation. Iron overload can be confirmed by magnetic resonance imaging, which shows a loss of signal intensity in affected tissues and avoids the need for liver biopsy.

The serum ferritin level, an acute phase reactant, may be elevated for reasons other than iron overload, including infection and malignancy; in such cases, the iron saturation is usually normal. In patients with liver disease, iron overload is not restricted to patients with genetic hemochromatosis. In nonalcoholic fatty liver disease (NAFLD), up to one-third of patients have an elevated iron saturation (> 45%) and an elevated serum ferritin level. Iron accumulation in NAFLD can occur in hepatocytes, the reticuloendothelial system, or both. Deposition of iron in the reticuloendothelial system has been implicated in more severe liver disease (steatohepatitis and fibrosis) in NAFLD. Hepatic iron accumulation is also frequent in alcohol-associated liver disease. In chronic hepatitis B and C, accumulation of hepatic iron is also recognized.

Dr. Martin is chief of the division of digestive health and liver diseases at the Miller School of Medicine, University of Miami, where he is the Mandel Chair of Gastroenterology. Dr. Friedman is the Anton R. Fried, MD, Chair of the department of medicine at Newton-Wellesley Hospital in Newton, Massachusetts, and assistant chief of medicine at Massachusetts General Hospital, and a professor of medicine at Harvard Medical School and Tufts University School of Medicine, all in Boston. The authors disclosed no conflicts. Previously published in Gastro Hep Advances. 2023 Oct 12. doi: 10.1016/j.gastha.2023.10.004.

Violence against women by partners is a serious human rights violation and a significant global public health issue. Overall, an estimated 27% of women aged 15-49 years who have been in a relationship have experienced physical or sexual violence (SV) at the hands of a partner. According to 2019 data from the US Department of Justice, SV in the United States occurs every 73 seconds, with child victims every 9 minutes. Lifetime rates of SV are around 17%-18% for women and 3% for men.

The emergency department remains the most common place where patients who have experienced SV seek comprehensive care, including emergency contraception, prophylaxis against sexually transmitted infections, forensic evidence collection for rape cases, and treatment for injuries.

Physical injuries from SV are not always detectable. Studies report variable percentages, ranging from 30%-80% of patients with traumatic SV injuries. Evidence regarding their severity is conflicting. Genital injuries are more common in assaults by acquaintances and in victims not using hormonal contraceptives.

The presence or absence of anogenital injuries following SV is a factor that can influence both victims’ willingness to report a crime and the judicial decision-making process regarding accusations and convictions. 

Rape Myths

The mythology of rape has been under discussion for more than 50 years, encompassing concerns that rape myths reinforce ideas about what does and does not constitute SV and who is a credible victim.

Rape myths, classically defined in the 1980s, are “prejudiced, stereotyped, and false beliefs about rape, rape victims, and rapists,” designed to “deny or minimize perceived harm or blame victims for their victimization.” The concept remains relevant to contemporary societal beliefs and concerns.

A systematic review analyzed elements of rape myths related to victim characteristics and their impact on credibility and blame attribution in the investigative process. Victims who knew the (male) perpetrator and were deemed provocative based on attire were assigned greater blame. In addition, detail and consistency in victims› statements and the presence of physical evidence and injuries increased credibility. However, in certain situations, rape myths may lead to blaming victims who do not fit the “real victim” stereotype, thus resulting in secondary victimization or revictimization.

Anogenital Injuries 

Anogenital injuries can occur in relation to consensual sexual activity (CSA), and SV may not be associated with injuries. Therefore, the presence of anogenital injuries does not “prove” SV nor does their absence exclude rape.

This statement is supported by a systematic review and meta-analysis investigating the prevalence of anogenital injuries in women following SV and CSA, using consistent examination techniques for better forensic evidence evaluation in criminal proceedings.

The following two groups were defined for comparison: SV, indicating any nonconsensual sexual contact with the survivor’s anogenital area, and CSA, representing the same type of sexual contact with participants’ consent.

The outcome measure was the presence of anogenital injury (defined as any genital, anal, or perineal injury detected using described techniques in each study). With no universal definition of genital trauma, the result assessment was dichotomous: The presence or absence of injury.

The systematic search yielded 1401 results, and 10 cohort studies published from 1997 to 2022 met the inclusion criteria. The study participants were 3165 women, with 59% (1874/3165) surviving SV.

Anogenital injuries were found in 48% of women who experienced SV (901/1874) and in 31% of those with CSA (394/1291). Anogenital injuries were significantly more likely in women who had experienced SV, compared with those with CSA (risk ratio, 1.59; P < .001). However, both groups had cases where anogenital injuries were either detected or not.

Some SV survivors had no identified anogenital injuries, and women examined after CSA had detectable anogenital injuries. Subgroup analysis for high-quality studies showed no significant differences between groups. These data support the hypothesis that the presence of anogenital injuries does not prove SV, and the absence of injuries does not disprove it.

Point for Practice

Numerous myths reinforce cultural attitudes toward reporting SV. One myth suggests that physical violence, and thus injuries, are inevitable accompaniments to rape. If the victim does not react physically, it might be argued that it was not really rape, or without physical trauma, one might be less inclined to believe that a rape occurred.

Physicians and healthcare professionals involved in the care and support of SV survivors must explicitly reassure them that the lack of anogenital injury evidence does not diminish the credibility of their account.
 

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

Violence against women by partners is a serious human rights violation and a significant global public health issue. Overall, an estimated 27% of women aged 15-49 years who have been in a relationship have experienced physical or sexual violence (SV) at the hands of a partner. According to 2019 data from the US Department of Justice, SV in the United States occurs every 73 seconds, with child victims every 9 minutes. Lifetime rates of SV are around 17%-18% for women and 3% for men.

The emergency department remains the most common place where patients who have experienced SV seek comprehensive care, including emergency contraception, prophylaxis against sexually transmitted infections, forensic evidence collection for rape cases, and treatment for injuries.

Physical injuries from SV are not always detectable. Studies report variable percentages, ranging from 30%-80% of patients with traumatic SV injuries. Evidence regarding their severity is conflicting. Genital injuries are more common in assaults by acquaintances and in victims not using hormonal contraceptives.

The presence or absence of anogenital injuries following SV is a factor that can influence both victims’ willingness to report a crime and the judicial decision-making process regarding accusations and convictions. 

Rape Myths

The mythology of rape has been under discussion for more than 50 years, encompassing concerns that rape myths reinforce ideas about what does and does not constitute SV and who is a credible victim.

Rape myths, classically defined in the 1980s, are “prejudiced, stereotyped, and false beliefs about rape, rape victims, and rapists,” designed to “deny or minimize perceived harm or blame victims for their victimization.” The concept remains relevant to contemporary societal beliefs and concerns.

A systematic review analyzed elements of rape myths related to victim characteristics and their impact on credibility and blame attribution in the investigative process. Victims who knew the (male) perpetrator and were deemed provocative based on attire were assigned greater blame. In addition, detail and consistency in victims› statements and the presence of physical evidence and injuries increased credibility. However, in certain situations, rape myths may lead to blaming victims who do not fit the “real victim” stereotype, thus resulting in secondary victimization or revictimization.

Anogenital Injuries 

Anogenital injuries can occur in relation to consensual sexual activity (CSA), and SV may not be associated with injuries. Therefore, the presence of anogenital injuries does not “prove” SV nor does their absence exclude rape.

This statement is supported by a systematic review and meta-analysis investigating the prevalence of anogenital injuries in women following SV and CSA, using consistent examination techniques for better forensic evidence evaluation in criminal proceedings.

The following two groups were defined for comparison: SV, indicating any nonconsensual sexual contact with the survivor’s anogenital area, and CSA, representing the same type of sexual contact with participants’ consent.

The outcome measure was the presence of anogenital injury (defined as any genital, anal, or perineal injury detected using described techniques in each study). With no universal definition of genital trauma, the result assessment was dichotomous: The presence or absence of injury.

The systematic search yielded 1401 results, and 10 cohort studies published from 1997 to 2022 met the inclusion criteria. The study participants were 3165 women, with 59% (1874/3165) surviving SV.

Anogenital injuries were found in 48% of women who experienced SV (901/1874) and in 31% of those with CSA (394/1291). Anogenital injuries were significantly more likely in women who had experienced SV, compared with those with CSA (risk ratio, 1.59; P < .001). However, both groups had cases where anogenital injuries were either detected or not.

Some SV survivors had no identified anogenital injuries, and women examined after CSA had detectable anogenital injuries. Subgroup analysis for high-quality studies showed no significant differences between groups. These data support the hypothesis that the presence of anogenital injuries does not prove SV, and the absence of injuries does not disprove it.

Point for Practice

Numerous myths reinforce cultural attitudes toward reporting SV. One myth suggests that physical violence, and thus injuries, are inevitable accompaniments to rape. If the victim does not react physically, it might be argued that it was not really rape, or without physical trauma, one might be less inclined to believe that a rape occurred.

Physicians and healthcare professionals involved in the care and support of SV survivors must explicitly reassure them that the lack of anogenital injury evidence does not diminish the credibility of their account.
 

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

Violence against women by partners is a serious human rights violation and a significant global public health issue. Overall, an estimated 27% of women aged 15-49 years who have been in a relationship have experienced physical or sexual violence (SV) at the hands of a partner. According to 2019 data from the US Department of Justice, SV in the United States occurs every 73 seconds, with child victims every 9 minutes. Lifetime rates of SV are around 17%-18% for women and 3% for men.

The emergency department remains the most common place where patients who have experienced SV seek comprehensive care, including emergency contraception, prophylaxis against sexually transmitted infections, forensic evidence collection for rape cases, and treatment for injuries.

Physical injuries from SV are not always detectable. Studies report variable percentages, ranging from 30%-80% of patients with traumatic SV injuries. Evidence regarding their severity is conflicting. Genital injuries are more common in assaults by acquaintances and in victims not using hormonal contraceptives.

The presence or absence of anogenital injuries following SV is a factor that can influence both victims’ willingness to report a crime and the judicial decision-making process regarding accusations and convictions. 

Rape Myths

The mythology of rape has been under discussion for more than 50 years, encompassing concerns that rape myths reinforce ideas about what does and does not constitute SV and who is a credible victim.

Rape myths, classically defined in the 1980s, are “prejudiced, stereotyped, and false beliefs about rape, rape victims, and rapists,” designed to “deny or minimize perceived harm or blame victims for their victimization.” The concept remains relevant to contemporary societal beliefs and concerns.

A systematic review analyzed elements of rape myths related to victim characteristics and their impact on credibility and blame attribution in the investigative process. Victims who knew the (male) perpetrator and were deemed provocative based on attire were assigned greater blame. In addition, detail and consistency in victims› statements and the presence of physical evidence and injuries increased credibility. However, in certain situations, rape myths may lead to blaming victims who do not fit the “real victim” stereotype, thus resulting in secondary victimization or revictimization.

Anogenital Injuries 

Anogenital injuries can occur in relation to consensual sexual activity (CSA), and SV may not be associated with injuries. Therefore, the presence of anogenital injuries does not “prove” SV nor does their absence exclude rape.

This statement is supported by a systematic review and meta-analysis investigating the prevalence of anogenital injuries in women following SV and CSA, using consistent examination techniques for better forensic evidence evaluation in criminal proceedings.

The following two groups were defined for comparison: SV, indicating any nonconsensual sexual contact with the survivor’s anogenital area, and CSA, representing the same type of sexual contact with participants’ consent.

The outcome measure was the presence of anogenital injury (defined as any genital, anal, or perineal injury detected using described techniques in each study). With no universal definition of genital trauma, the result assessment was dichotomous: The presence or absence of injury.

The systematic search yielded 1401 results, and 10 cohort studies published from 1997 to 2022 met the inclusion criteria. The study participants were 3165 women, with 59% (1874/3165) surviving SV.

Anogenital injuries were found in 48% of women who experienced SV (901/1874) and in 31% of those with CSA (394/1291). Anogenital injuries were significantly more likely in women who had experienced SV, compared with those with CSA (risk ratio, 1.59; P < .001). However, both groups had cases where anogenital injuries were either detected or not.

Some SV survivors had no identified anogenital injuries, and women examined after CSA had detectable anogenital injuries. Subgroup analysis for high-quality studies showed no significant differences between groups. These data support the hypothesis that the presence of anogenital injuries does not prove SV, and the absence of injuries does not disprove it.

Point for Practice

Numerous myths reinforce cultural attitudes toward reporting SV. One myth suggests that physical violence, and thus injuries, are inevitable accompaniments to rape. If the victim does not react physically, it might be argued that it was not really rape, or without physical trauma, one might be less inclined to believe that a rape occurred.

Physicians and healthcare professionals involved in the care and support of SV survivors must explicitly reassure them that the lack of anogenital injury evidence does not diminish the credibility of their account.
 

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

Patients with type 2 diabetes and their clinicians may not share the same priorities when it comes to choosing a second-line drug after metformin, new research suggested.

In a mixed-methods study of 40 people with type 2 diabetes and moderate heart disease risk who were asked about their goals, preferences, and priorities for glucose-lowering medications, their answers were surprisingly heterogeneous and not always aligned with those endorsed by the medical community.

Notably, most patients rated blindness and death as the most important health outcomes to avoid and efficacy in lowering blood glucose and A1c as the most important medication attributes. Avoidance of cardiovascular outcomes was ranked slightly lower. The data were published recently in Clinical Diabetes.

“We really need to ask our patients about what is important to them. That’s how you have a relationship and engage in shared decision-making,” lead author Rozalina G. McCoy, MD, Associate Division Chief for Clinical Research in the Division of Endocrinology, Diabetes, and Nutrition at the University of Maryland, Baltimore, told this news organization.

Patient education should be approached in that way, she added. “They might not think their diabetes is related to heart disease risk or that anything they do can impact it. That’s a conversation starter ... We first have to understand what motivates them and then tailor education to what is important to them,” she said.

Asked to comment, endocrinologist Cecilia C. Low Wang, MD, Professor of Medicine at the University of Colorado, Aurora, told this news organization, “the fact that death and blindness are key health outcomes in the patients surveyed indicates to me that patients place great importance on ‘irreversible’ bad outcomes. We as clinicians do not tend to discuss benefits for all-cause mortality with our diabetes medications. Maybe we should include this in our discussions.”

Dr. Low Wang also noted, as did Dr. McCoy, that the emphasis on lowering glucose reflects decades of public health messaging, and that while it’s certainly important, particularly for microvascular outcomes, it’s just one of several factors influencing cardiovascular and all-cause mortality risk.

“I think what this finding tells us is that we need to focus on a more nuanced message of improved glycemic control and reduction of risk of both micro- and macrovascular complications and weight management, healthy diet, and regular physical activity ... that it is not just glycemic control that is important but glycemic control in the context of a healthy lifestyle and good overall health,” Dr. Low Wang said.

Blindness and Death Bigger Concerns Than Heart Attack or Heart Failure

The study participants included 25 from the Mayo Health System in Rochester, Minnesota (where McCoy formerly worked), and 15 from Grady Memorial Hospital in Atlanta, Georgia. Half were White, and just over a third were Black. All had active prescriptions for a glucagon-like peptide 1 receptor agonist, sodium-glucose cotransporter 2 inhibitor, dipeptidyl peptidase 4 inhibitor, and/or a sulfonylurea.

They were first given a multistep ranking exercise regarding health outcomes and medication attributes selected from a list and then were asked to add any others that were important to them and re-ranked the entire list.

For health outcomes, the most common listed as “very important” were blindness (63%) and death (60%), followed by heart attack (48%) and heart failure (48%). Those endorsed less often were hospital admission (28%), severe hypoglycemia (25%), and pancreatitis (15%).

Dr. Low Wang noted, “Heart attack and heart failure and stroke were not far behind ... Maybe the messaging about risks of [atherosclerotic cardiovascular disease] in diabetes is working at least to some degree and in some populations.”

Combinations of outcomes selected as “very important” varied widely, with just one combination (end-stage kidney disease, heart attack, blindness, and any event causing death) endorsed by more than a single participant. This was unexpected, Dr. McCoy noted.

“Usually, a qualitative study is very small, so we thought 40 was huge and we’d see a lot of similar things, but I think the first surprising finding was just how much variability there is in what people with type 2 diabetes consider as motivating factors for choosing a diabetes medication ... So when we talk about patient-centered care and shared decision-making, that’s really important because patient priorities are very different,” she said.

For medication attributes, greater reductions in blood glucose and A1c were most often endorsed as “very important” (68%), followed by oral administration (45%) and absence of gastrointestinal side effects (38%).

Nearly half (47.5%) added one or more outcomes as important to them in deciding on a medication for type 2 diabetes. The most common had to do with affordability (n = 10), minimizing the total number of drugs (n = 3) and avoiding drowsiness (n = 2).

Dr. Low Wang said, “Some of the health outcomes we as clinicians feel are important, such as serious infection, hospitalization, kidney dysfunction or failure, and diabetic foot problems, were not felt to be as important to the patients surveyed. This could be due to other health outcomes outweighing these, or highlights the need for more focus, education, and discussion with patients.”

Five Themes Describe Patients’ Perceptions of Health Outcomes

Throughout the ranking process, a researcher asked participants (via phone or Zoom) about their reasons for ranking items as “very important” or “not very important” in choosing medications. For health outcomes, five broad themes emerged from their comments: The outcome’s severity (with permanence and potential lethality prominent), their perceived personal susceptibility to it, salience (ie, whether they knew someone who had experienced the outcome), their beliefs about causation, and about the consequences of the outcome.

With medication attributes, the medication’s ability to lower blood glucose was deemed a priority by nearly all. By contrast, there was much more variation in the responses regarding the influence of various side effects in their decision-making based on personal preferences, beliefs, and previous experiences.

This paper is one part of research funded by the Patient-Centered Outcomes Research Institute (PCORI) examining the effects of second-line glucose-lowering medications in patients with type 2 diabetes who are at moderate, rather than high, cardiovascular risk. The main paper, looking at prespecified cardiovascular outcomes, is scheduled to be published soon, Dr. McCoy said.

She’s now planning a follow-up study to look at actual outcomes for the second-line drugs based on the patients’ preferences. “We don’t have the evidence necessarily to tell our patients what is best given their specific preferences ... The question is, if our patients tell us what they want, how would that change what we recommend to them?”

The study was funded by PCORI. Dr. McCoy received support from the National Institutes of Health and AARP. She also served as a consultant to Emmi (Wolters Kluwer) for developing patient education materials related to prediabetes and diabetes. Dr. Low Wang received research support from Dexcom Inc, Virta Health, and CellResearch Corp within the past 24 months.
 

A version of this article appeared on Medscape.com.

Patients with type 2 diabetes and their clinicians may not share the same priorities when it comes to choosing a second-line drug after metformin, new research suggested.

In a mixed-methods study of 40 people with type 2 diabetes and moderate heart disease risk who were asked about their goals, preferences, and priorities for glucose-lowering medications, their answers were surprisingly heterogeneous and not always aligned with those endorsed by the medical community.

Notably, most patients rated blindness and death as the most important health outcomes to avoid and efficacy in lowering blood glucose and A1c as the most important medication attributes. Avoidance of cardiovascular outcomes was ranked slightly lower. The data were published recently in Clinical Diabetes.

“We really need to ask our patients about what is important to them. That’s how you have a relationship and engage in shared decision-making,” lead author Rozalina G. McCoy, MD, Associate Division Chief for Clinical Research in the Division of Endocrinology, Diabetes, and Nutrition at the University of Maryland, Baltimore, told this news organization.

Patient education should be approached in that way, she added. “They might not think their diabetes is related to heart disease risk or that anything they do can impact it. That’s a conversation starter ... We first have to understand what motivates them and then tailor education to what is important to them,” she said.

Asked to comment, endocrinologist Cecilia C. Low Wang, MD, Professor of Medicine at the University of Colorado, Aurora, told this news organization, “the fact that death and blindness are key health outcomes in the patients surveyed indicates to me that patients place great importance on ‘irreversible’ bad outcomes. We as clinicians do not tend to discuss benefits for all-cause mortality with our diabetes medications. Maybe we should include this in our discussions.”

Dr. Low Wang also noted, as did Dr. McCoy, that the emphasis on lowering glucose reflects decades of public health messaging, and that while it’s certainly important, particularly for microvascular outcomes, it’s just one of several factors influencing cardiovascular and all-cause mortality risk.

“I think what this finding tells us is that we need to focus on a more nuanced message of improved glycemic control and reduction of risk of both micro- and macrovascular complications and weight management, healthy diet, and regular physical activity ... that it is not just glycemic control that is important but glycemic control in the context of a healthy lifestyle and good overall health,” Dr. Low Wang said.

Blindness and Death Bigger Concerns Than Heart Attack or Heart Failure

The study participants included 25 from the Mayo Health System in Rochester, Minnesota (where McCoy formerly worked), and 15 from Grady Memorial Hospital in Atlanta, Georgia. Half were White, and just over a third were Black. All had active prescriptions for a glucagon-like peptide 1 receptor agonist, sodium-glucose cotransporter 2 inhibitor, dipeptidyl peptidase 4 inhibitor, and/or a sulfonylurea.

They were first given a multistep ranking exercise regarding health outcomes and medication attributes selected from a list and then were asked to add any others that were important to them and re-ranked the entire list.

For health outcomes, the most common listed as “very important” were blindness (63%) and death (60%), followed by heart attack (48%) and heart failure (48%). Those endorsed less often were hospital admission (28%), severe hypoglycemia (25%), and pancreatitis (15%).

Dr. Low Wang noted, “Heart attack and heart failure and stroke were not far behind ... Maybe the messaging about risks of [atherosclerotic cardiovascular disease] in diabetes is working at least to some degree and in some populations.”

Combinations of outcomes selected as “very important” varied widely, with just one combination (end-stage kidney disease, heart attack, blindness, and any event causing death) endorsed by more than a single participant. This was unexpected, Dr. McCoy noted.

“Usually, a qualitative study is very small, so we thought 40 was huge and we’d see a lot of similar things, but I think the first surprising finding was just how much variability there is in what people with type 2 diabetes consider as motivating factors for choosing a diabetes medication ... So when we talk about patient-centered care and shared decision-making, that’s really important because patient priorities are very different,” she said.

For medication attributes, greater reductions in blood glucose and A1c were most often endorsed as “very important” (68%), followed by oral administration (45%) and absence of gastrointestinal side effects (38%).

Nearly half (47.5%) added one or more outcomes as important to them in deciding on a medication for type 2 diabetes. The most common had to do with affordability (n = 10), minimizing the total number of drugs (n = 3) and avoiding drowsiness (n = 2).

Dr. Low Wang said, “Some of the health outcomes we as clinicians feel are important, such as serious infection, hospitalization, kidney dysfunction or failure, and diabetic foot problems, were not felt to be as important to the patients surveyed. This could be due to other health outcomes outweighing these, or highlights the need for more focus, education, and discussion with patients.”

Five Themes Describe Patients’ Perceptions of Health Outcomes

Throughout the ranking process, a researcher asked participants (via phone or Zoom) about their reasons for ranking items as “very important” or “not very important” in choosing medications. For health outcomes, five broad themes emerged from their comments: The outcome’s severity (with permanence and potential lethality prominent), their perceived personal susceptibility to it, salience (ie, whether they knew someone who had experienced the outcome), their beliefs about causation, and about the consequences of the outcome.

With medication attributes, the medication’s ability to lower blood glucose was deemed a priority by nearly all. By contrast, there was much more variation in the responses regarding the influence of various side effects in their decision-making based on personal preferences, beliefs, and previous experiences.

This paper is one part of research funded by the Patient-Centered Outcomes Research Institute (PCORI) examining the effects of second-line glucose-lowering medications in patients with type 2 diabetes who are at moderate, rather than high, cardiovascular risk. The main paper, looking at prespecified cardiovascular outcomes, is scheduled to be published soon, Dr. McCoy said.

She’s now planning a follow-up study to look at actual outcomes for the second-line drugs based on the patients’ preferences. “We don’t have the evidence necessarily to tell our patients what is best given their specific preferences ... The question is, if our patients tell us what they want, how would that change what we recommend to them?”

The study was funded by PCORI. Dr. McCoy received support from the National Institutes of Health and AARP. She also served as a consultant to Emmi (Wolters Kluwer) for developing patient education materials related to prediabetes and diabetes. Dr. Low Wang received research support from Dexcom Inc, Virta Health, and CellResearch Corp within the past 24 months.
 

A version of this article appeared on Medscape.com.

Patients with type 2 diabetes and their clinicians may not share the same priorities when it comes to choosing a second-line drug after metformin, new research suggested.

In a mixed-methods study of 40 people with type 2 diabetes and moderate heart disease risk who were asked about their goals, preferences, and priorities for glucose-lowering medications, their answers were surprisingly heterogeneous and not always aligned with those endorsed by the medical community.

Notably, most patients rated blindness and death as the most important health outcomes to avoid and efficacy in lowering blood glucose and A1c as the most important medication attributes. Avoidance of cardiovascular outcomes was ranked slightly lower. The data were published recently in Clinical Diabetes.

“We really need to ask our patients about what is important to them. That’s how you have a relationship and engage in shared decision-making,” lead author Rozalina G. McCoy, MD, Associate Division Chief for Clinical Research in the Division of Endocrinology, Diabetes, and Nutrition at the University of Maryland, Baltimore, told this news organization.

Patient education should be approached in that way, she added. “They might not think their diabetes is related to heart disease risk or that anything they do can impact it. That’s a conversation starter ... We first have to understand what motivates them and then tailor education to what is important to them,” she said.

Asked to comment, endocrinologist Cecilia C. Low Wang, MD, Professor of Medicine at the University of Colorado, Aurora, told this news organization, “the fact that death and blindness are key health outcomes in the patients surveyed indicates to me that patients place great importance on ‘irreversible’ bad outcomes. We as clinicians do not tend to discuss benefits for all-cause mortality with our diabetes medications. Maybe we should include this in our discussions.”

Dr. Low Wang also noted, as did Dr. McCoy, that the emphasis on lowering glucose reflects decades of public health messaging, and that while it’s certainly important, particularly for microvascular outcomes, it’s just one of several factors influencing cardiovascular and all-cause mortality risk.

“I think what this finding tells us is that we need to focus on a more nuanced message of improved glycemic control and reduction of risk of both micro- and macrovascular complications and weight management, healthy diet, and regular physical activity ... that it is not just glycemic control that is important but glycemic control in the context of a healthy lifestyle and good overall health,” Dr. Low Wang said.

Blindness and Death Bigger Concerns Than Heart Attack or Heart Failure

The study participants included 25 from the Mayo Health System in Rochester, Minnesota (where McCoy formerly worked), and 15 from Grady Memorial Hospital in Atlanta, Georgia. Half were White, and just over a third were Black. All had active prescriptions for a glucagon-like peptide 1 receptor agonist, sodium-glucose cotransporter 2 inhibitor, dipeptidyl peptidase 4 inhibitor, and/or a sulfonylurea.

They were first given a multistep ranking exercise regarding health outcomes and medication attributes selected from a list and then were asked to add any others that were important to them and re-ranked the entire list.

For health outcomes, the most common listed as “very important” were blindness (63%) and death (60%), followed by heart attack (48%) and heart failure (48%). Those endorsed less often were hospital admission (28%), severe hypoglycemia (25%), and pancreatitis (15%).

Dr. Low Wang noted, “Heart attack and heart failure and stroke were not far behind ... Maybe the messaging about risks of [atherosclerotic cardiovascular disease] in diabetes is working at least to some degree and in some populations.”

Combinations of outcomes selected as “very important” varied widely, with just one combination (end-stage kidney disease, heart attack, blindness, and any event causing death) endorsed by more than a single participant. This was unexpected, Dr. McCoy noted.

“Usually, a qualitative study is very small, so we thought 40 was huge and we’d see a lot of similar things, but I think the first surprising finding was just how much variability there is in what people with type 2 diabetes consider as motivating factors for choosing a diabetes medication ... So when we talk about patient-centered care and shared decision-making, that’s really important because patient priorities are very different,” she said.

For medication attributes, greater reductions in blood glucose and A1c were most often endorsed as “very important” (68%), followed by oral administration (45%) and absence of gastrointestinal side effects (38%).

Nearly half (47.5%) added one or more outcomes as important to them in deciding on a medication for type 2 diabetes. The most common had to do with affordability (n = 10), minimizing the total number of drugs (n = 3) and avoiding drowsiness (n = 2).

Dr. Low Wang said, “Some of the health outcomes we as clinicians feel are important, such as serious infection, hospitalization, kidney dysfunction or failure, and diabetic foot problems, were not felt to be as important to the patients surveyed. This could be due to other health outcomes outweighing these, or highlights the need for more focus, education, and discussion with patients.”

Five Themes Describe Patients’ Perceptions of Health Outcomes

Throughout the ranking process, a researcher asked participants (via phone or Zoom) about their reasons for ranking items as “very important” or “not very important” in choosing medications. For health outcomes, five broad themes emerged from their comments: The outcome’s severity (with permanence and potential lethality prominent), their perceived personal susceptibility to it, salience (ie, whether they knew someone who had experienced the outcome), their beliefs about causation, and about the consequences of the outcome.

With medication attributes, the medication’s ability to lower blood glucose was deemed a priority by nearly all. By contrast, there was much more variation in the responses regarding the influence of various side effects in their decision-making based on personal preferences, beliefs, and previous experiences.

This paper is one part of research funded by the Patient-Centered Outcomes Research Institute (PCORI) examining the effects of second-line glucose-lowering medications in patients with type 2 diabetes who are at moderate, rather than high, cardiovascular risk. The main paper, looking at prespecified cardiovascular outcomes, is scheduled to be published soon, Dr. McCoy said.

She’s now planning a follow-up study to look at actual outcomes for the second-line drugs based on the patients’ preferences. “We don’t have the evidence necessarily to tell our patients what is best given their specific preferences ... The question is, if our patients tell us what they want, how would that change what we recommend to them?”

The study was funded by PCORI. Dr. McCoy received support from the National Institutes of Health and AARP. She also served as a consultant to Emmi (Wolters Kluwer) for developing patient education materials related to prediabetes and diabetes. Dr. Low Wang received research support from Dexcom Inc, Virta Health, and CellResearch Corp within the past 24 months.
 

A version of this article appeared on Medscape.com.

The patient had an advanced cutaneous squamous cell carcinoma (cSCC) on the face that seemed to be affecting the facial nerve, ruling out aggressive surgery. When Mohs surgery failed to clear the tumor, radiation was ordered. But the best option — an immune checkpoint inhibitor — could not be administered because the patient was a lung transplant recipient.

Although approved for metastatic cSCC, immune checkpoint inhibitors are associated with a higher potential for rejection of an organ transplant.

“The feeling is that the risk of rejection is just too great if we were to try to give an immune checkpoint inhibitor,” said Sean Christensen, MD, PhD, director of dermatologic surgery at Yale Dermatology–Branford, in Connecticut, who was treating the patient. Dr. Christensen consulted with the transplant team, and together they decided to switch the patient to sirolimus, an immunosuppressant that has been shown to have less risk of promoting skin cancer in those who take the medication. Sirolimus, however, is not as well tolerated as the usual first-line immunosuppressant, tacrolimus.

Dr. Christensen

Dr. Bottomley

Reducing Risk Factors

Dr. Bottomley said that there’s also been renewed effort to identify how to reduce cSCC risk in transplant recipients through recently developed consensus guidelines and a proposed decision framework developed by Dr. Bottomley and colleagues. The evidence will help clinicians have “greater confidence in making early interventions,” he said.

Currently, solid organ transplant patients are told to reduce sun exposure, in part because the majority of cSCCs occur in sun-exposed areas, such as the head and neck, and ultraviolet radiation leads to mutations. “Sun protection is critical,” Dr. Christensen said. That’s especially true in younger transplant recipients, who may have decades of sun exposure, he said.

The immunosuppressive medications also increase cancer risk, for a variety of reasons. One of the more-commonly used immunosuppressants in the past, azathioprine, is itself carcinogenic. Other antirejection medications, such as tacrolimus and mycophenolate, may also induce mutagenic changes that give rise to malignancies, according to the paper by Dr. Bibee, assistant professor of dermatology at Johns Hopkins, Baltimore.

Both Dr. Bibee, in her paper, and Dr. Arron, in an interview, noted that voriconazole, an antifungal used to prevent Aspergillus infection after lung transplant, has been associated with an increase in cSCC in lung transplant recipients.

Dr. Arron

In addition, immunosuppression essentially “blocks the body’s immune system from recognizing that there are abnormal cancerous cells present,” Dr. Arron, a dermatologist in private practice in Burlingame, California, told this news organization.

Previously, while at the High-Risk Skin Cancer Program at University of California, San Francisco (UCSF), Dr. Arron and others studied whether human papillomavirus (HPV) might play a role in spurring the development of cSCC formation in the immunocompromised. HPV is highly prevalent on the skin, but the virus found on the skin tends to be composed of lower-risk strains.

“In our research, we did not find any biologic mechanism by which this virus might be driving these cancers,” said Dr. Arron, although she said that some researchers “feel very strongly that HPV must be in some way a driver.”

Dr. Bottomley believes that HPV’s role has not been completely determined. The excess incidence of cSCC suggests a virus might be involved, as has been seen with excess risk of lymphoma in patients with Epstein-Barr virus, he said.

Some of his research is focusing on whether advanced immune aging is an independent risk factor for subsequent cSCC development in solid organ transplant recipients. The immune system undergoes changes as people age, and the speed of this process varies from patient to patient, which means immune age can be different from chronological age, said Dr. Bottomley. “We’re still exploring why immune aging should predispose you to cSCC,” he said.
 

When to Intervene?

Transplant patients are followed by dermatologists at regular intervals. But guidelines are not consistent on the recommended timing of those intervals.

Dr. Arron and colleagues in 2019 created a risk prediction module that recommended frequency of follow-up based on low, medium, high, or very high risk. The tool is available to clinicians in an app called SUNTRAC, or the Skin and Ultraviolet Neoplasia Transplant Risk Assessment Calculator.

A question that Dr. Arron said dermatologists and transplant specialists have wrangled with: How early can they intervene to prevent further lesions?

In the 2022 decision framework paper in Transplant International, Dr. Bottomley and dermatology colleagues from around the world attempted to better delineate when and how clinicians should intervene when a cSCC is first detected. That first cSCC “should be regarded as a ‘red flag’ heralding an increased risk of further skin cancers and possibly internal malignancies,” the authors wrote. That moment is “a key opportunity to proactively consider secondary preventive strategies,” they wrote, but noted that the best interventions and “their sequencing remain unclear,” indicating the need for further research.
 

Coordinating With the Transplant Team

A key strategy to help prevent cSCC development — suggested in Dr. Bottomley’s paper, and by Dr. Arron and Dr. Christensen — is to consult with the transplant team on potentially changing a patient’s immunosuppressive medication or reducing the dose.

Dr. Arron said that a decade ago, it was somewhat of a novel concept, requiring data-sharing and making personal connections with the transplant team to forge trusting relationships. By the time she left UCSF a few years ago, she said, “the transplant program was very much on board with preventing and treating skin cancer and oftentimes they were making changes even before I would suggest them.”

Suggesting a change or dose reduction is not undertaken lightly. “Our transplant physician colleagues are balancing multiple problems in very sick patients, of which skin cancer might be one, but not the most pressing one in the setting of other transplant complications,” said Dr. Arron.

Dr. Bottomley said that “as transplant physicians, we very much respect and value the input of our dermatology colleagues,” but agreed that many factors “outside malignancy risk” must be weighed when considering changing an immunosuppressive regimen.

In a Delphi Consensus Statement on prevention of cSCC in organ transplant recipients, published in 2021 in JAMA Dermatology, the authors recommended having discussions about immunosuppression with transplant specialists, but did not make a recommendation on what strategy to use. The consensus panel said it preferred “to defer this decision to transplant physicians.”

Acitretin a Go, Nicotinamide Not So Much

Outside of changing an immunosuppressive regimen, among the interventions for secondary prevention are acitretin, the systemic retinoid, and nicotinamide, a form of niacin.

Dr. Christensen conducted a small retrospective investigation evaluating the effectiveness of acitretin in reducing cSCC in both immunocompromised and immunocompetent patients who had received care at Yale, which was recently published in the Journal of the American Academy of Dermatology. Acitretin reduced invasive cSCC by about 75% in both patient groups — a surprising result for the immunocompetent group, but well-established in patients who have had a solid organ transplant. But acitretin had no effect on cSCC in situ or basal cell carcinoma. “The benefit of acitretin is primarily in preventing the invasive SCC,” said Dr. Christensen, which is why he tends to reserve it for patients who have already had several cSCCs.

“It’s not a completely benign medication,” he said, noting the need for monitoring for cholesterol and liver function.

Several years ago, a study in immunocompetent patients, published in the New England Journal of Medicine, found that nicotinamide (also known as niacinamide) reduced the rate of nonmelonoma skin cancer by 23%, giving clinicians hope that it might also be a low-risk, low-cost cancer preventive for solid organ transplant patients. But enthusiasm has dampened since a 2023 study in the New England Journal of Medicine found that the vitamin did not reduce cSCCs in transplant recipients.

Dr. Christensen said he believes the most-recent study wasn’t powered to detect a 25% reduction in cancers. “It’s certainly possible that it still works exactly the same way in transplant patients that it does in immunocompetent patients,” he said. “There’s very little risk of recommending it to patients for general prevention. But it probably has a very modest effect in many,” he said.

Dr. Arron agreed, saying, “it may be that we simply need bigger studies to achieve that statistical significance.” Even so, she said she would not use the therapy “until there is more evidence supporting the use of nicotinamide in transplant recipients.”

Immune checkpoint inhibitors such as cemiplimab and pembrolizumab have been approved by the US Food and Drug Administration for advanced cSCC; nivolumab is another drug in the same class that has not yet been approved for cSCC. But “there’s always been a fear — and a legitimate fear — that if you gave those to organ transplant recipients they would reject their organ,” said Dr. Christensen.

Patients who take the checkpoint inhibitors may first have to stop taking their antirejection drugs, leaving them at risk. It also appears that the checkpoint inhibitors themselves contribute to organ rejection. Recent studies suggest that “the rate of organ rejection is only about 30% to 40%,” with the checkpoint inhibitors, said Dr. Christensen. “Obviously that’s still not an ideal outcome,” he said, but noted that with patients who have inoperable metastatic cSCC, “immune therapy can be a good option.”

Dr. Christensen reported no disclosures. Dr. Bottomley has previously received speaker fees and an educational grant from Astellas. Dr. Arron disclosed ties with Regeneron, Castle Biosciences, and Enspectra Health, not specific to transplantation.

The patient had an advanced cutaneous squamous cell carcinoma (cSCC) on the face that seemed to be affecting the facial nerve, ruling out aggressive surgery. When Mohs surgery failed to clear the tumor, radiation was ordered. But the best option — an immune checkpoint inhibitor — could not be administered because the patient was a lung transplant recipient.

Although approved for metastatic cSCC, immune checkpoint inhibitors are associated with a higher potential for rejection of an organ transplant.

“The feeling is that the risk of rejection is just too great if we were to try to give an immune checkpoint inhibitor,” said Sean Christensen, MD, PhD, director of dermatologic surgery at Yale Dermatology–Branford, in Connecticut, who was treating the patient. Dr. Christensen consulted with the transplant team, and together they decided to switch the patient to sirolimus, an immunosuppressant that has been shown to have less risk of promoting skin cancer in those who take the medication. Sirolimus, however, is not as well tolerated as the usual first-line immunosuppressant, tacrolimus.

Dr. Christensen

Dr. Bottomley

Reducing Risk Factors

Dr. Bottomley said that there’s also been renewed effort to identify how to reduce cSCC risk in transplant recipients through recently developed consensus guidelines and a proposed decision framework developed by Dr. Bottomley and colleagues. The evidence will help clinicians have “greater confidence in making early interventions,” he said.

Currently, solid organ transplant patients are told to reduce sun exposure, in part because the majority of cSCCs occur in sun-exposed areas, such as the head and neck, and ultraviolet radiation leads to mutations. “Sun protection is critical,” Dr. Christensen said. That’s especially true in younger transplant recipients, who may have decades of sun exposure, he said.

The immunosuppressive medications also increase cancer risk, for a variety of reasons. One of the more-commonly used immunosuppressants in the past, azathioprine, is itself carcinogenic. Other antirejection medications, such as tacrolimus and mycophenolate, may also induce mutagenic changes that give rise to malignancies, according to the paper by Dr. Bibee, assistant professor of dermatology at Johns Hopkins, Baltimore.

Both Dr. Bibee, in her paper, and Dr. Arron, in an interview, noted that voriconazole, an antifungal used to prevent Aspergillus infection after lung transplant, has been associated with an increase in cSCC in lung transplant recipients.

Dr. Arron

In addition, immunosuppression essentially “blocks the body’s immune system from recognizing that there are abnormal cancerous cells present,” Dr. Arron, a dermatologist in private practice in Burlingame, California, told this news organization.

Previously, while at the High-Risk Skin Cancer Program at University of California, San Francisco (UCSF), Dr. Arron and others studied whether human papillomavirus (HPV) might play a role in spurring the development of cSCC formation in the immunocompromised. HPV is highly prevalent on the skin, but the virus found on the skin tends to be composed of lower-risk strains.

“In our research, we did not find any biologic mechanism by which this virus might be driving these cancers,” said Dr. Arron, although she said that some researchers “feel very strongly that HPV must be in some way a driver.”

Dr. Bottomley believes that HPV’s role has not been completely determined. The excess incidence of cSCC suggests a virus might be involved, as has been seen with excess risk of lymphoma in patients with Epstein-Barr virus, he said.

Some of his research is focusing on whether advanced immune aging is an independent risk factor for subsequent cSCC development in solid organ transplant recipients. The immune system undergoes changes as people age, and the speed of this process varies from patient to patient, which means immune age can be different from chronological age, said Dr. Bottomley. “We’re still exploring why immune aging should predispose you to cSCC,” he said.
 

When to Intervene?

Transplant patients are followed by dermatologists at regular intervals. But guidelines are not consistent on the recommended timing of those intervals.

Dr. Arron and colleagues in 2019 created a risk prediction module that recommended frequency of follow-up based on low, medium, high, or very high risk. The tool is available to clinicians in an app called SUNTRAC, or the Skin and Ultraviolet Neoplasia Transplant Risk Assessment Calculator.

A question that Dr. Arron said dermatologists and transplant specialists have wrangled with: How early can they intervene to prevent further lesions?

In the 2022 decision framework paper in Transplant International, Dr. Bottomley and dermatology colleagues from around the world attempted to better delineate when and how clinicians should intervene when a cSCC is first detected. That first cSCC “should be regarded as a ‘red flag’ heralding an increased risk of further skin cancers and possibly internal malignancies,” the authors wrote. That moment is “a key opportunity to proactively consider secondary preventive strategies,” they wrote, but noted that the best interventions and “their sequencing remain unclear,” indicating the need for further research.
 

Coordinating With the Transplant Team

A key strategy to help prevent cSCC development — suggested in Dr. Bottomley’s paper, and by Dr. Arron and Dr. Christensen — is to consult with the transplant team on potentially changing a patient’s immunosuppressive medication or reducing the dose.

Dr. Arron said that a decade ago, it was somewhat of a novel concept, requiring data-sharing and making personal connections with the transplant team to forge trusting relationships. By the time she left UCSF a few years ago, she said, “the transplant program was very much on board with preventing and treating skin cancer and oftentimes they were making changes even before I would suggest them.”

Suggesting a change or dose reduction is not undertaken lightly. “Our transplant physician colleagues are balancing multiple problems in very sick patients, of which skin cancer might be one, but not the most pressing one in the setting of other transplant complications,” said Dr. Arron.

Dr. Bottomley said that “as transplant physicians, we very much respect and value the input of our dermatology colleagues,” but agreed that many factors “outside malignancy risk” must be weighed when considering changing an immunosuppressive regimen.

In a Delphi Consensus Statement on prevention of cSCC in organ transplant recipients, published in 2021 in JAMA Dermatology, the authors recommended having discussions about immunosuppression with transplant specialists, but did not make a recommendation on what strategy to use. The consensus panel said it preferred “to defer this decision to transplant physicians.”

Acitretin a Go, Nicotinamide Not So Much

Outside of changing an immunosuppressive regimen, among the interventions for secondary prevention are acitretin, the systemic retinoid, and nicotinamide, a form of niacin.

Dr. Christensen conducted a small retrospective investigation evaluating the effectiveness of acitretin in reducing cSCC in both immunocompromised and immunocompetent patients who had received care at Yale, which was recently published in the Journal of the American Academy of Dermatology. Acitretin reduced invasive cSCC by about 75% in both patient groups — a surprising result for the immunocompetent group, but well-established in patients who have had a solid organ transplant. But acitretin had no effect on cSCC in situ or basal cell carcinoma. “The benefit of acitretin is primarily in preventing the invasive SCC,” said Dr. Christensen, which is why he tends to reserve it for patients who have already had several cSCCs.

“It’s not a completely benign medication,” he said, noting the need for monitoring for cholesterol and liver function.

Several years ago, a study in immunocompetent patients, published in the New England Journal of Medicine, found that nicotinamide (also known as niacinamide) reduced the rate of nonmelonoma skin cancer by 23%, giving clinicians hope that it might also be a low-risk, low-cost cancer preventive for solid organ transplant patients. But enthusiasm has dampened since a 2023 study in the New England Journal of Medicine found that the vitamin did not reduce cSCCs in transplant recipients.

Dr. Christensen said he believes the most-recent study wasn’t powered to detect a 25% reduction in cancers. “It’s certainly possible that it still works exactly the same way in transplant patients that it does in immunocompetent patients,” he said. “There’s very little risk of recommending it to patients for general prevention. But it probably has a very modest effect in many,” he said.

Dr. Arron agreed, saying, “it may be that we simply need bigger studies to achieve that statistical significance.” Even so, she said she would not use the therapy “until there is more evidence supporting the use of nicotinamide in transplant recipients.”

Immune checkpoint inhibitors such as cemiplimab and pembrolizumab have been approved by the US Food and Drug Administration for advanced cSCC; nivolumab is another drug in the same class that has not yet been approved for cSCC. But “there’s always been a fear — and a legitimate fear — that if you gave those to organ transplant recipients they would reject their organ,” said Dr. Christensen.

Patients who take the checkpoint inhibitors may first have to stop taking their antirejection drugs, leaving them at risk. It also appears that the checkpoint inhibitors themselves contribute to organ rejection. Recent studies suggest that “the rate of organ rejection is only about 30% to 40%,” with the checkpoint inhibitors, said Dr. Christensen. “Obviously that’s still not an ideal outcome,” he said, but noted that with patients who have inoperable metastatic cSCC, “immune therapy can be a good option.”

Dr. Christensen reported no disclosures. Dr. Bottomley has previously received speaker fees and an educational grant from Astellas. Dr. Arron disclosed ties with Regeneron, Castle Biosciences, and Enspectra Health, not specific to transplantation.

The patient had an advanced cutaneous squamous cell carcinoma (cSCC) on the face that seemed to be affecting the facial nerve, ruling out aggressive surgery. When Mohs surgery failed to clear the tumor, radiation was ordered. But the best option — an immune checkpoint inhibitor — could not be administered because the patient was a lung transplant recipient.

Although approved for metastatic cSCC, immune checkpoint inhibitors are associated with a higher potential for rejection of an organ transplant.

“The feeling is that the risk of rejection is just too great if we were to try to give an immune checkpoint inhibitor,” said Sean Christensen, MD, PhD, director of dermatologic surgery at Yale Dermatology–Branford, in Connecticut, who was treating the patient. Dr. Christensen consulted with the transplant team, and together they decided to switch the patient to sirolimus, an immunosuppressant that has been shown to have less risk of promoting skin cancer in those who take the medication. Sirolimus, however, is not as well tolerated as the usual first-line immunosuppressant, tacrolimus.

Dr. Christensen

Dr. Bottomley

Reducing Risk Factors

Dr. Bottomley said that there’s also been renewed effort to identify how to reduce cSCC risk in transplant recipients through recently developed consensus guidelines and a proposed decision framework developed by Dr. Bottomley and colleagues. The evidence will help clinicians have “greater confidence in making early interventions,” he said.

Currently, solid organ transplant patients are told to reduce sun exposure, in part because the majority of cSCCs occur in sun-exposed areas, such as the head and neck, and ultraviolet radiation leads to mutations. “Sun protection is critical,” Dr. Christensen said. That’s especially true in younger transplant recipients, who may have decades of sun exposure, he said.

The immunosuppressive medications also increase cancer risk, for a variety of reasons. One of the more-commonly used immunosuppressants in the past, azathioprine, is itself carcinogenic. Other antirejection medications, such as tacrolimus and mycophenolate, may also induce mutagenic changes that give rise to malignancies, according to the paper by Dr. Bibee, assistant professor of dermatology at Johns Hopkins, Baltimore.

Both Dr. Bibee, in her paper, and Dr. Arron, in an interview, noted that voriconazole, an antifungal used to prevent Aspergillus infection after lung transplant, has been associated with an increase in cSCC in lung transplant recipients.

Dr. Arron

In addition, immunosuppression essentially “blocks the body’s immune system from recognizing that there are abnormal cancerous cells present,” Dr. Arron, a dermatologist in private practice in Burlingame, California, told this news organization.

Previously, while at the High-Risk Skin Cancer Program at University of California, San Francisco (UCSF), Dr. Arron and others studied whether human papillomavirus (HPV) might play a role in spurring the development of cSCC formation in the immunocompromised. HPV is highly prevalent on the skin, but the virus found on the skin tends to be composed of lower-risk strains.

“In our research, we did not find any biologic mechanism by which this virus might be driving these cancers,” said Dr. Arron, although she said that some researchers “feel very strongly that HPV must be in some way a driver.”

Dr. Bottomley believes that HPV’s role has not been completely determined. The excess incidence of cSCC suggests a virus might be involved, as has been seen with excess risk of lymphoma in patients with Epstein-Barr virus, he said.

Some of his research is focusing on whether advanced immune aging is an independent risk factor for subsequent cSCC development in solid organ transplant recipients. The immune system undergoes changes as people age, and the speed of this process varies from patient to patient, which means immune age can be different from chronological age, said Dr. Bottomley. “We’re still exploring why immune aging should predispose you to cSCC,” he said.
 

When to Intervene?

Transplant patients are followed by dermatologists at regular intervals. But guidelines are not consistent on the recommended timing of those intervals.

Dr. Arron and colleagues in 2019 created a risk prediction module that recommended frequency of follow-up based on low, medium, high, or very high risk. The tool is available to clinicians in an app called SUNTRAC, or the Skin and Ultraviolet Neoplasia Transplant Risk Assessment Calculator.

A question that Dr. Arron said dermatologists and transplant specialists have wrangled with: How early can they intervene to prevent further lesions?

In the 2022 decision framework paper in Transplant International, Dr. Bottomley and dermatology colleagues from around the world attempted to better delineate when and how clinicians should intervene when a cSCC is first detected. That first cSCC “should be regarded as a ‘red flag’ heralding an increased risk of further skin cancers and possibly internal malignancies,” the authors wrote. That moment is “a key opportunity to proactively consider secondary preventive strategies,” they wrote, but noted that the best interventions and “their sequencing remain unclear,” indicating the need for further research.
 

Coordinating With the Transplant Team

A key strategy to help prevent cSCC development — suggested in Dr. Bottomley’s paper, and by Dr. Arron and Dr. Christensen — is to consult with the transplant team on potentially changing a patient’s immunosuppressive medication or reducing the dose.

Dr. Arron said that a decade ago, it was somewhat of a novel concept, requiring data-sharing and making personal connections with the transplant team to forge trusting relationships. By the time she left UCSF a few years ago, she said, “the transplant program was very much on board with preventing and treating skin cancer and oftentimes they were making changes even before I would suggest them.”

Suggesting a change or dose reduction is not undertaken lightly. “Our transplant physician colleagues are balancing multiple problems in very sick patients, of which skin cancer might be one, but not the most pressing one in the setting of other transplant complications,” said Dr. Arron.

Dr. Bottomley said that “as transplant physicians, we very much respect and value the input of our dermatology colleagues,” but agreed that many factors “outside malignancy risk” must be weighed when considering changing an immunosuppressive regimen.

In a Delphi Consensus Statement on prevention of cSCC in organ transplant recipients, published in 2021 in JAMA Dermatology, the authors recommended having discussions about immunosuppression with transplant specialists, but did not make a recommendation on what strategy to use. The consensus panel said it preferred “to defer this decision to transplant physicians.”

Acitretin a Go, Nicotinamide Not So Much

Outside of changing an immunosuppressive regimen, among the interventions for secondary prevention are acitretin, the systemic retinoid, and nicotinamide, a form of niacin.

Dr. Christensen conducted a small retrospective investigation evaluating the effectiveness of acitretin in reducing cSCC in both immunocompromised and immunocompetent patients who had received care at Yale, which was recently published in the Journal of the American Academy of Dermatology. Acitretin reduced invasive cSCC by about 75% in both patient groups — a surprising result for the immunocompetent group, but well-established in patients who have had a solid organ transplant. But acitretin had no effect on cSCC in situ or basal cell carcinoma. “The benefit of acitretin is primarily in preventing the invasive SCC,” said Dr. Christensen, which is why he tends to reserve it for patients who have already had several cSCCs.

“It’s not a completely benign medication,” he said, noting the need for monitoring for cholesterol and liver function.

Several years ago, a study in immunocompetent patients, published in the New England Journal of Medicine, found that nicotinamide (also known as niacinamide) reduced the rate of nonmelonoma skin cancer by 23%, giving clinicians hope that it might also be a low-risk, low-cost cancer preventive for solid organ transplant patients. But enthusiasm has dampened since a 2023 study in the New England Journal of Medicine found that the vitamin did not reduce cSCCs in transplant recipients.

Dr. Christensen said he believes the most-recent study wasn’t powered to detect a 25% reduction in cancers. “It’s certainly possible that it still works exactly the same way in transplant patients that it does in immunocompetent patients,” he said. “There’s very little risk of recommending it to patients for general prevention. But it probably has a very modest effect in many,” he said.

Dr. Arron agreed, saying, “it may be that we simply need bigger studies to achieve that statistical significance.” Even so, she said she would not use the therapy “until there is more evidence supporting the use of nicotinamide in transplant recipients.”

Immune checkpoint inhibitors such as cemiplimab and pembrolizumab have been approved by the US Food and Drug Administration for advanced cSCC; nivolumab is another drug in the same class that has not yet been approved for cSCC. But “there’s always been a fear — and a legitimate fear — that if you gave those to organ transplant recipients they would reject their organ,” said Dr. Christensen.

Patients who take the checkpoint inhibitors may first have to stop taking their antirejection drugs, leaving them at risk. It also appears that the checkpoint inhibitors themselves contribute to organ rejection. Recent studies suggest that “the rate of organ rejection is only about 30% to 40%,” with the checkpoint inhibitors, said Dr. Christensen. “Obviously that’s still not an ideal outcome,” he said, but noted that with patients who have inoperable metastatic cSCC, “immune therapy can be a good option.”

Dr. Christensen reported no disclosures. Dr. Bottomley has previously received speaker fees and an educational grant from Astellas. Dr. Arron disclosed ties with Regeneron, Castle Biosciences, and Enspectra Health, not specific to transplantation.

There is insufficient evidence that drugs targeting the Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway increase the risk of cardiovascular or thrombotic complications in people undergoing treatment for a variety of dermatological conditions, at least in the short term, say the authors of a new meta-analysis published in JAMA Dermatology.

Considering data on over 17,000 patients with different dermatoses from 45 placebo-controlled randomized clinical trials with an average follow up of 16 weeks, they found there was no significant increase in the occurrence of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) in people with dermatoses treated with JAK-STAT inhibitors, compared with placebo.

The I² statistic was 0.00% for both MACE and VTE comparing the two arms, indicating that the results were unlikely to be due to chance. There was no increased risk in MACE between those on placebo and those on JAK-STAT inhibitors, with a risk ratio (RR) of 0.47; or for VTE risk, with an RR of 0.46.

Similar findings were obtained when data were analyzed according to the dermatological condition being treated, mechanism of action of the medication, or whether the medication carried a boxed warning.

These data “suggest inconsistency with established sentiments,” that JAK-STAT inhibitors increase the risk for cardiovascular events, Patrick Ireland, MD, of the University of New South Wales, Randwick, Australia, and coauthors wrote in the article. “This may be owing to the limited time frames in which these rare events could be adequately captured, or the ages of enrolled patients being too young to realize the well established heightened risks of developing MACE and VTE,” they suggested.

However, the findings challenge the notion that the cardiovascular complications of these drugs are the same in all patients; dermatological use may not be associated with the same risks as with use for rheumatologic indications.
 

Class-Wide Boxed Warning

“JAK-STAT [inhibitors] have had some pretty indemnifying data against their use, with the ORAL [Surveillance] study demonstrating increased all-cause mortality, cardiovascular events, venous thromboembolism, and malignancy,” Dr. Ireland said in an interview.

ORAL Surveillance was an open-label, postmarketing trial conducted in patients with rheumatoid arthritis treated with tofacitinib or a tumor necrosis factor (TNF) inhibitor. The results led the US Food and Drug Administration to require information about the risks of serious heart-related events, cancer, blood clots, and death in a boxed warning for JAK-STAT inhibitors in 2022.

“I think it’s important to recognize that these [ORAL Surveillance participants] are very different patients to the typical dermatological patient being treated with a JAK-STAT [inhibitors], with newer studies demonstrating a much safer profile than initially thought,” Dr. Ireland said.
 

Examining Risk in Dermatological Conditions

The meta-analysis performed by Dr. Ireland and associates focused specifically on the risk for MACE and VTE in patients being treated for dermatological conditions, and included trials published up until June 2023. Only trials that had included a placebo arm were considered; pooled analyses, long-term extension trial data, post hoc analyses, and pediatric-specific trials were excluded.

Most (25) of the trials were phase 2b or phase 3 trials, 18 were phase 2 to 2b, and two were phase 1 trials. The studies included 12,996 participants, mostly with atopic dermatitis or psoriasis, who were treated with JAK-STAT inhibitors, which included baricitinib (2846 patients), tofacitinib (2470), upadacitinib (2218), abrocitinib (1904), and deucravacitinib (1492), among others. There were 4925 patients on placebo.

Overall, MACE — defined as a combined endpoint of acute myocardial infarction, stroke, cardiovascular mortality, heart failure, and unstable angina, as well as arterial embolism — occurred in 13 of the JAK-STAT inhibitor-treated patients and in four of those on placebo. VTE — defined as deep vein thrombosis, pulmonary embolism, and any unusual site thrombosis — was reported in eight JAK-STAT inhibitor-treated patients and in one patient on placebo.

The pooled incidence ratios for MACE and VTE were calculated as 0.20 per 100 person exposure years (PEY) for JAK-STAT inhibitor treatment and 0.13 PEY for placebo. The pooled RRs comparing the two treatment groups were a respective 1.13 for MACE and 2.79 for VTE, but neither RR reached statistical significance.

No difference was seen between the treatment arms in terms of treatment emergent adverse events (RR, 1.05), serious adverse events (RR, 0.92), or study discontinuation because of adverse events (RR, 0.94).
 

Reassuring Results?

Dr. Ireland and coauthors said the finding should help to reassure clinicians that the short-term use of JAK-STAT inhibitors in patients with dermatological conditions with low cardiovascular risk profiles “appears to be both safe and well tolerated.” They cautioned, however, that “clinicians must remain judicious” when using these medications for longer periods and in high-risk patient populations.

This was a pragmatic meta-analysis that provides useful information for dermatologists, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, said in an interview.

“When there are safety concerns, I think that’s where data like this are so important to not just allay the fears of practitioners, but also to arm the practitioner with information for when they discuss a possible treatment with a patient,” said Dr. Friedman, who was not involved in the study.

“What’s unique here is that they’re looking at any possible use of JAK inhibitors for dermatological disease,” so this represents patients that dermatologists would be seeing, he added.

“The limitation here is time, we only can say so much about the safety of the medication with the data that we have,” Dr. Friedman said. Almost 4 months is “a good amount of time” to know about the cardiovascular risks, he said, but added, what happens then? Will the risk increase and will patients need to be switched to another medication?

“There’s no line in the sand,” with regard to using a JAK-STAT inhibitor. “If you look at the label, they’re not meant to be used incrementally,” but as ongoing treatment, while considering the needs of the patient and the relative risks and benefits, he said.

With that in mind, “the open label extension studies for all these [JAK-STAT inhibitors] are really, really important to get a sense of ‘do new signals emerge down the road.’ ”

The meta-analysis received no commercial funding. One author of the work reported personal fees from several pharmaceutical companies which were done outside of analysis. Dr. Friedman has received research funding from or acted as a consultant for several pharmaceutical companies including, Incyte, Pfizer, Eli Lily, and AbbVie.

There is insufficient evidence that drugs targeting the Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway increase the risk of cardiovascular or thrombotic complications in people undergoing treatment for a variety of dermatological conditions, at least in the short term, say the authors of a new meta-analysis published in JAMA Dermatology.

Considering data on over 17,000 patients with different dermatoses from 45 placebo-controlled randomized clinical trials with an average follow up of 16 weeks, they found there was no significant increase in the occurrence of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) in people with dermatoses treated with JAK-STAT inhibitors, compared with placebo.

The I² statistic was 0.00% for both MACE and VTE comparing the two arms, indicating that the results were unlikely to be due to chance. There was no increased risk in MACE between those on placebo and those on JAK-STAT inhibitors, with a risk ratio (RR) of 0.47; or for VTE risk, with an RR of 0.46.

Similar findings were obtained when data were analyzed according to the dermatological condition being treated, mechanism of action of the medication, or whether the medication carried a boxed warning.

These data “suggest inconsistency with established sentiments,” that JAK-STAT inhibitors increase the risk for cardiovascular events, Patrick Ireland, MD, of the University of New South Wales, Randwick, Australia, and coauthors wrote in the article. “This may be owing to the limited time frames in which these rare events could be adequately captured, or the ages of enrolled patients being too young to realize the well established heightened risks of developing MACE and VTE,” they suggested.

However, the findings challenge the notion that the cardiovascular complications of these drugs are the same in all patients; dermatological use may not be associated with the same risks as with use for rheumatologic indications.
 

Class-Wide Boxed Warning

“JAK-STAT [inhibitors] have had some pretty indemnifying data against their use, with the ORAL [Surveillance] study demonstrating increased all-cause mortality, cardiovascular events, venous thromboembolism, and malignancy,” Dr. Ireland said in an interview.

ORAL Surveillance was an open-label, postmarketing trial conducted in patients with rheumatoid arthritis treated with tofacitinib or a tumor necrosis factor (TNF) inhibitor. The results led the US Food and Drug Administration to require information about the risks of serious heart-related events, cancer, blood clots, and death in a boxed warning for JAK-STAT inhibitors in 2022.

“I think it’s important to recognize that these [ORAL Surveillance participants] are very different patients to the typical dermatological patient being treated with a JAK-STAT [inhibitors], with newer studies demonstrating a much safer profile than initially thought,” Dr. Ireland said.
 

Examining Risk in Dermatological Conditions

The meta-analysis performed by Dr. Ireland and associates focused specifically on the risk for MACE and VTE in patients being treated for dermatological conditions, and included trials published up until June 2023. Only trials that had included a placebo arm were considered; pooled analyses, long-term extension trial data, post hoc analyses, and pediatric-specific trials were excluded.

Most (25) of the trials were phase 2b or phase 3 trials, 18 were phase 2 to 2b, and two were phase 1 trials. The studies included 12,996 participants, mostly with atopic dermatitis or psoriasis, who were treated with JAK-STAT inhibitors, which included baricitinib (2846 patients), tofacitinib (2470), upadacitinib (2218), abrocitinib (1904), and deucravacitinib (1492), among others. There were 4925 patients on placebo.

Overall, MACE — defined as a combined endpoint of acute myocardial infarction, stroke, cardiovascular mortality, heart failure, and unstable angina, as well as arterial embolism — occurred in 13 of the JAK-STAT inhibitor-treated patients and in four of those on placebo. VTE — defined as deep vein thrombosis, pulmonary embolism, and any unusual site thrombosis — was reported in eight JAK-STAT inhibitor-treated patients and in one patient on placebo.

The pooled incidence ratios for MACE and VTE were calculated as 0.20 per 100 person exposure years (PEY) for JAK-STAT inhibitor treatment and 0.13 PEY for placebo. The pooled RRs comparing the two treatment groups were a respective 1.13 for MACE and 2.79 for VTE, but neither RR reached statistical significance.

No difference was seen between the treatment arms in terms of treatment emergent adverse events (RR, 1.05), serious adverse events (RR, 0.92), or study discontinuation because of adverse events (RR, 0.94).
 

Reassuring Results?

Dr. Ireland and coauthors said the finding should help to reassure clinicians that the short-term use of JAK-STAT inhibitors in patients with dermatological conditions with low cardiovascular risk profiles “appears to be both safe and well tolerated.” They cautioned, however, that “clinicians must remain judicious” when using these medications for longer periods and in high-risk patient populations.

This was a pragmatic meta-analysis that provides useful information for dermatologists, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, said in an interview.

“When there are safety concerns, I think that’s where data like this are so important to not just allay the fears of practitioners, but also to arm the practitioner with information for when they discuss a possible treatment with a patient,” said Dr. Friedman, who was not involved in the study.

“What’s unique here is that they’re looking at any possible use of JAK inhibitors for dermatological disease,” so this represents patients that dermatologists would be seeing, he added.

“The limitation here is time, we only can say so much about the safety of the medication with the data that we have,” Dr. Friedman said. Almost 4 months is “a good amount of time” to know about the cardiovascular risks, he said, but added, what happens then? Will the risk increase and will patients need to be switched to another medication?

“There’s no line in the sand,” with regard to using a JAK-STAT inhibitor. “If you look at the label, they’re not meant to be used incrementally,” but as ongoing treatment, while considering the needs of the patient and the relative risks and benefits, he said.

With that in mind, “the open label extension studies for all these [JAK-STAT inhibitors] are really, really important to get a sense of ‘do new signals emerge down the road.’ ”

The meta-analysis received no commercial funding. One author of the work reported personal fees from several pharmaceutical companies which were done outside of analysis. Dr. Friedman has received research funding from or acted as a consultant for several pharmaceutical companies including, Incyte, Pfizer, Eli Lily, and AbbVie.

There is insufficient evidence that drugs targeting the Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway increase the risk of cardiovascular or thrombotic complications in people undergoing treatment for a variety of dermatological conditions, at least in the short term, say the authors of a new meta-analysis published in JAMA Dermatology.

Considering data on over 17,000 patients with different dermatoses from 45 placebo-controlled randomized clinical trials with an average follow up of 16 weeks, they found there was no significant increase in the occurrence of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) in people with dermatoses treated with JAK-STAT inhibitors, compared with placebo.

The I² statistic was 0.00% for both MACE and VTE comparing the two arms, indicating that the results were unlikely to be due to chance. There was no increased risk in MACE between those on placebo and those on JAK-STAT inhibitors, with a risk ratio (RR) of 0.47; or for VTE risk, with an RR of 0.46.

Similar findings were obtained when data were analyzed according to the dermatological condition being treated, mechanism of action of the medication, or whether the medication carried a boxed warning.

These data “suggest inconsistency with established sentiments,” that JAK-STAT inhibitors increase the risk for cardiovascular events, Patrick Ireland, MD, of the University of New South Wales, Randwick, Australia, and coauthors wrote in the article. “This may be owing to the limited time frames in which these rare events could be adequately captured, or the ages of enrolled patients being too young to realize the well established heightened risks of developing MACE and VTE,” they suggested.

However, the findings challenge the notion that the cardiovascular complications of these drugs are the same in all patients; dermatological use may not be associated with the same risks as with use for rheumatologic indications.
 

Class-Wide Boxed Warning

“JAK-STAT [inhibitors] have had some pretty indemnifying data against their use, with the ORAL [Surveillance] study demonstrating increased all-cause mortality, cardiovascular events, venous thromboembolism, and malignancy,” Dr. Ireland said in an interview.

ORAL Surveillance was an open-label, postmarketing trial conducted in patients with rheumatoid arthritis treated with tofacitinib or a tumor necrosis factor (TNF) inhibitor. The results led the US Food and Drug Administration to require information about the risks of serious heart-related events, cancer, blood clots, and death in a boxed warning for JAK-STAT inhibitors in 2022.

“I think it’s important to recognize that these [ORAL Surveillance participants] are very different patients to the typical dermatological patient being treated with a JAK-STAT [inhibitors], with newer studies demonstrating a much safer profile than initially thought,” Dr. Ireland said.
 

Examining Risk in Dermatological Conditions

The meta-analysis performed by Dr. Ireland and associates focused specifically on the risk for MACE and VTE in patients being treated for dermatological conditions, and included trials published up until June 2023. Only trials that had included a placebo arm were considered; pooled analyses, long-term extension trial data, post hoc analyses, and pediatric-specific trials were excluded.

Most (25) of the trials were phase 2b or phase 3 trials, 18 were phase 2 to 2b, and two were phase 1 trials. The studies included 12,996 participants, mostly with atopic dermatitis or psoriasis, who were treated with JAK-STAT inhibitors, which included baricitinib (2846 patients), tofacitinib (2470), upadacitinib (2218), abrocitinib (1904), and deucravacitinib (1492), among others. There were 4925 patients on placebo.

Overall, MACE — defined as a combined endpoint of acute myocardial infarction, stroke, cardiovascular mortality, heart failure, and unstable angina, as well as arterial embolism — occurred in 13 of the JAK-STAT inhibitor-treated patients and in four of those on placebo. VTE — defined as deep vein thrombosis, pulmonary embolism, and any unusual site thrombosis — was reported in eight JAK-STAT inhibitor-treated patients and in one patient on placebo.

The pooled incidence ratios for MACE and VTE were calculated as 0.20 per 100 person exposure years (PEY) for JAK-STAT inhibitor treatment and 0.13 PEY for placebo. The pooled RRs comparing the two treatment groups were a respective 1.13 for MACE and 2.79 for VTE, but neither RR reached statistical significance.

No difference was seen between the treatment arms in terms of treatment emergent adverse events (RR, 1.05), serious adverse events (RR, 0.92), or study discontinuation because of adverse events (RR, 0.94).
 

Reassuring Results?

Dr. Ireland and coauthors said the finding should help to reassure clinicians that the short-term use of JAK-STAT inhibitors in patients with dermatological conditions with low cardiovascular risk profiles “appears to be both safe and well tolerated.” They cautioned, however, that “clinicians must remain judicious” when using these medications for longer periods and in high-risk patient populations.

This was a pragmatic meta-analysis that provides useful information for dermatologists, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, said in an interview.

“When there are safety concerns, I think that’s where data like this are so important to not just allay the fears of practitioners, but also to arm the practitioner with information for when they discuss a possible treatment with a patient,” said Dr. Friedman, who was not involved in the study.

“What’s unique here is that they’re looking at any possible use of JAK inhibitors for dermatological disease,” so this represents patients that dermatologists would be seeing, he added.

“The limitation here is time, we only can say so much about the safety of the medication with the data that we have,” Dr. Friedman said. Almost 4 months is “a good amount of time” to know about the cardiovascular risks, he said, but added, what happens then? Will the risk increase and will patients need to be switched to another medication?

“There’s no line in the sand,” with regard to using a JAK-STAT inhibitor. “If you look at the label, they’re not meant to be used incrementally,” but as ongoing treatment, while considering the needs of the patient and the relative risks and benefits, he said.

With that in mind, “the open label extension studies for all these [JAK-STAT inhibitors] are really, really important to get a sense of ‘do new signals emerge down the road.’ ”

The meta-analysis received no commercial funding. One author of the work reported personal fees from several pharmaceutical companies which were done outside of analysis. Dr. Friedman has received research funding from or acted as a consultant for several pharmaceutical companies including, Incyte, Pfizer, Eli Lily, and AbbVie.

The AGA Research Foundation plays an important role in medical research by providing grants to young scientists at a critical time in their career. AGA’s flagship award is the Research Scholar Award, which provides career development support for young investigators in gastroenterology and hepatology research. In the last 10 years, the AGA Research Foundation has funded 63 young scientists through a Research Scholar Award grant.

“I want to express my sincere gratitude to the AGA Research Foundation and its benefactors. At this fragile and critical juncture, this AGA Research Scholar Award offers an unmatched opportunity to pursue the type of high-impact scientific work that allows a junior investigator such as myself to achieve the necessary momentum to create a nationally competitive research program,” states Alexander , MD, PhD, the Regent of the University of California, Los Angeles, 2023 AGA Research Scholar Award recipient.

Funded by the generosity of donors, the AGA Research Foundation’s research award program ensures that we are building a community of researchers whose work serves the greater community and benefits all our patients.

By joining others in supporting the AGA Research Foundation, you will ensure that young researchers have opportunities to continue their life-saving work. Your tax-deductible contribution supports the foundation’s research award program, including the Research Scholar Award, which ensures that studies are funded, discoveries are made, and patients are treated. Learn more or make a contribution at www.foundation.gastro.org.

The AGA Research Foundation plays an important role in medical research by providing grants to young scientists at a critical time in their career. AGA’s flagship award is the Research Scholar Award, which provides career development support for young investigators in gastroenterology and hepatology research. In the last 10 years, the AGA Research Foundation has funded 63 young scientists through a Research Scholar Award grant.

“I want to express my sincere gratitude to the AGA Research Foundation and its benefactors. At this fragile and critical juncture, this AGA Research Scholar Award offers an unmatched opportunity to pursue the type of high-impact scientific work that allows a junior investigator such as myself to achieve the necessary momentum to create a nationally competitive research program,” states Alexander , MD, PhD, the Regent of the University of California, Los Angeles, 2023 AGA Research Scholar Award recipient.

Funded by the generosity of donors, the AGA Research Foundation’s research award program ensures that we are building a community of researchers whose work serves the greater community and benefits all our patients.

By joining others in supporting the AGA Research Foundation, you will ensure that young researchers have opportunities to continue their life-saving work. Your tax-deductible contribution supports the foundation’s research award program, including the Research Scholar Award, which ensures that studies are funded, discoveries are made, and patients are treated. Learn more or make a contribution at www.foundation.gastro.org.

The AGA Research Foundation plays an important role in medical research by providing grants to young scientists at a critical time in their career. AGA’s flagship award is the Research Scholar Award, which provides career development support for young investigators in gastroenterology and hepatology research. In the last 10 years, the AGA Research Foundation has funded 63 young scientists through a Research Scholar Award grant.

“I want to express my sincere gratitude to the AGA Research Foundation and its benefactors. At this fragile and critical juncture, this AGA Research Scholar Award offers an unmatched opportunity to pursue the type of high-impact scientific work that allows a junior investigator such as myself to achieve the necessary momentum to create a nationally competitive research program,” states Alexander , MD, PhD, the Regent of the University of California, Los Angeles, 2023 AGA Research Scholar Award recipient.

Funded by the generosity of donors, the AGA Research Foundation’s research award program ensures that we are building a community of researchers whose work serves the greater community and benefits all our patients.

By joining others in supporting the AGA Research Foundation, you will ensure that young researchers have opportunities to continue their life-saving work. Your tax-deductible contribution supports the foundation’s research award program, including the Research Scholar Award, which ensures that studies are funded, discoveries are made, and patients are treated. Learn more or make a contribution at www.foundation.gastro.org.

TOPLINE:

Protein intake within 4 hours before exercise may shorten hypoglycemic episodes during moderate physical activity in teens with type 1 diabetes (T1D).

METHODOLOGY:

• For teenagers with T1D, regular physical activity improves blood sugar, insulin sensitivity, and other health measures, but the risk for hypoglycemia is a major barrier.
• In a secondary analysis of the FLEX study, researchers estimated the association between protein intake within 4 hours before moderate to vigorous physical activity bouts and glycemia during and following physical exercise.
• The final sample size included 447 bouts from 112 adolescents with T1D (median age, 14.5 years; 53.6% female) whose physical activity records and 24-hour dietary recall data were collected at baseline and 6 months.
• Data on continuous glucose monitoring (CGM) was a selection criterium and used to calculate the following measures of glycemia:
• Percentage of time above range (TAR; > 180 mg/dL)
• Percentage of time in range (TIR; 70-180 mg/dL)
• Percentage of time below range (TBR; < 70 mg/dL)

TAKEAWAY:

• There was a small reduction in TBR during physical activity in patients who consumed 10-19.9 g (−4.41%; P = .04) and more than 20 g (−4.83%; P = .02) of protein before moderate to vigorous exercise compared with those who consumed less than 10 g of protein.
• Similarly, protein intakes of 0.125-0.249 g/kg and ≥ 0.25 g/kg were associated with −5.38% (P = .01) and −4.32% (P = .03) reductions in TBR, respectively, compared with less than 0.125 g/kg of protein intake.
• However, the pre-exercise protein consumption was not associated with TAR or TIR during exercise or with any glycemic measurements (TAR, TIR, and TBR) after exercise.
• The benefits of protein intake on glycemia were observed only during moderate-intensity bouts of physical activity, which may reflect differing glycemic trajectories in more high-intensity activity.

IN PRACTICE:

“Consumption of at least 10 g or 0.125 g/kg bodyweight was associated with reduced TBR during moderate to vigorous physical activity, indicating improved safety for adolescents with T1D,” the authors wrote.

SOURCE:

This study, led by Franklin R. Muntis, PhD, Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, North Carolina, was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

Self-reported measures of dietary intake were prone to underreporting, while moderate-to-vigorous physical activity was often overreported among adolescents. Approximately, 26% of identified bouts of moderate to vigorous physical activity were missing adequate CGM data, excluding participants from the analysis, which may have caused selection bias. There was no time-stamped insulin dosing data available.

DISCLOSURES:

The FLEX study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Protein intake within 4 hours before exercise may shorten hypoglycemic episodes during moderate physical activity in teens with type 1 diabetes (T1D).

METHODOLOGY:

• For teenagers with T1D, regular physical activity improves blood sugar, insulin sensitivity, and other health measures, but the risk for hypoglycemia is a major barrier.
• In a secondary analysis of the FLEX study, researchers estimated the association between protein intake within 4 hours before moderate to vigorous physical activity bouts and glycemia during and following physical exercise.
• The final sample size included 447 bouts from 112 adolescents with T1D (median age, 14.5 years; 53.6% female) whose physical activity records and 24-hour dietary recall data were collected at baseline and 6 months.
• Data on continuous glucose monitoring (CGM) was a selection criterium and used to calculate the following measures of glycemia:
• Percentage of time above range (TAR; > 180 mg/dL)
• Percentage of time in range (TIR; 70-180 mg/dL)
• Percentage of time below range (TBR; < 70 mg/dL)

TAKEAWAY:

• There was a small reduction in TBR during physical activity in patients who consumed 10-19.9 g (−4.41%; P = .04) and more than 20 g (−4.83%; P = .02) of protein before moderate to vigorous exercise compared with those who consumed less than 10 g of protein.
• Similarly, protein intakes of 0.125-0.249 g/kg and ≥ 0.25 g/kg were associated with −5.38% (P = .01) and −4.32% (P = .03) reductions in TBR, respectively, compared with less than 0.125 g/kg of protein intake.
• However, the pre-exercise protein consumption was not associated with TAR or TIR during exercise or with any glycemic measurements (TAR, TIR, and TBR) after exercise.
• The benefits of protein intake on glycemia were observed only during moderate-intensity bouts of physical activity, which may reflect differing glycemic trajectories in more high-intensity activity.

IN PRACTICE:

“Consumption of at least 10 g or 0.125 g/kg bodyweight was associated with reduced TBR during moderate to vigorous physical activity, indicating improved safety for adolescents with T1D,” the authors wrote.

SOURCE:

This study, led by Franklin R. Muntis, PhD, Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, North Carolina, was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

Self-reported measures of dietary intake were prone to underreporting, while moderate-to-vigorous physical activity was often overreported among adolescents. Approximately, 26% of identified bouts of moderate to vigorous physical activity were missing adequate CGM data, excluding participants from the analysis, which may have caused selection bias. There was no time-stamped insulin dosing data available.

DISCLOSURES:

The FLEX study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Protein intake within 4 hours before exercise may shorten hypoglycemic episodes during moderate physical activity in teens with type 1 diabetes (T1D).

METHODOLOGY:

• For teenagers with T1D, regular physical activity improves blood sugar, insulin sensitivity, and other health measures, but the risk for hypoglycemia is a major barrier.
• In a secondary analysis of the FLEX study, researchers estimated the association between protein intake within 4 hours before moderate to vigorous physical activity bouts and glycemia during and following physical exercise.
• The final sample size included 447 bouts from 112 adolescents with T1D (median age, 14.5 years; 53.6% female) whose physical activity records and 24-hour dietary recall data were collected at baseline and 6 months.
• Data on continuous glucose monitoring (CGM) was a selection criterium and used to calculate the following measures of glycemia:
• Percentage of time above range (TAR; > 180 mg/dL)
• Percentage of time in range (TIR; 70-180 mg/dL)
• Percentage of time below range (TBR; < 70 mg/dL)

TAKEAWAY:

• There was a small reduction in TBR during physical activity in patients who consumed 10-19.9 g (−4.41%; P = .04) and more than 20 g (−4.83%; P = .02) of protein before moderate to vigorous exercise compared with those who consumed less than 10 g of protein.
• Similarly, protein intakes of 0.125-0.249 g/kg and ≥ 0.25 g/kg were associated with −5.38% (P = .01) and −4.32% (P = .03) reductions in TBR, respectively, compared with less than 0.125 g/kg of protein intake.
• However, the pre-exercise protein consumption was not associated with TAR or TIR during exercise or with any glycemic measurements (TAR, TIR, and TBR) after exercise.
• The benefits of protein intake on glycemia were observed only during moderate-intensity bouts of physical activity, which may reflect differing glycemic trajectories in more high-intensity activity.

IN PRACTICE:

“Consumption of at least 10 g or 0.125 g/kg bodyweight was associated with reduced TBR during moderate to vigorous physical activity, indicating improved safety for adolescents with T1D,” the authors wrote.

SOURCE:

This study, led by Franklin R. Muntis, PhD, Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, North Carolina, was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

Self-reported measures of dietary intake were prone to underreporting, while moderate-to-vigorous physical activity was often overreported among adolescents. Approximately, 26% of identified bouts of moderate to vigorous physical activity were missing adequate CGM data, excluding participants from the analysis, which may have caused selection bias. There was no time-stamped insulin dosing data available.

DISCLOSURES:

The FLEX study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.