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Fewer than 1 out of 4 patients with HCV-related liver cancer receive antivirals
, and rates aren’t much better for patients seen by specialists, based on a retrospective analysis of private insurance claims.
The study also showed that patients receiving DAAs lived significantly longer, emphasizing the importance of prescribing these medications to all eligible patients, reported principal investigator Mindie H. Nguyen, MD, AGAF,, of Stanford University Medical Center, Palo Alto, California, and colleagues.
“Prior studies have shown evidence of improved survival among HCV-related HCC patients who received DAA treatment, but not much is known about the current DAA utilization among these patients in the general US population,” said lead author Leslie Y. Kam, MD, a postdoctoral scholar in gastroenterology at Stanford Medicine, who presented the findings in November at the annual meeting of the American Association for the Study of Liver Diseases.
To generate real-world data, the investigators analyzed medical records from 3922 patients in Optum’s Clinformatics Data Mart Database. All patients had private medical insurance and received care for HCV-related HCC between 2015 and 2021.
“Instead of using institutional databases which tend to bias toward highly specialized tertiary care center patients, our study uses a large, national sample of HCV-HCC patients that represents real-world DAA treatment rates and survival outcomes,” Dr. Kam said in a written comment.
Within this cohort, fewer than one out of four patients (23.5%) received DAA, a rate that Dr. Kam called “dismally low.”
Patients with either compensated or decompensated cirrhosis had higher treatment rates than those without cirrhosis (24.2% or 24.5%, respectively, vs. 16.2%; P = .001). The investigators noted that more than half of the patients had decompensated cirrhosis, suggesting that HCV-related HCC was diagnosed late in the disease course.
Receiving care from a gastroenterologist or infectious disease physician also was associated with a higher treatment rate. Patients managed by a gastroenterologist alone had a treatment rate of 27.0%, while those who received care from a gastroenterologist or infectious disease doctor alongside an oncologist had a treatment rate of 25.6%, versus just 9.4% for those who received care from an oncologist alone, and 12.4% among those who did not see a specialist of any kind (P = .005).
These findings highlight “the need for a multidisciplinary approach to care in this population,” Dr. Kam suggested.
Echoing previous research, DAAs were associated with extended survival. A significantly greater percentage of patients who received DAA were alive after 5 years, compared with patients who did not receive DAA (47.2% vs. 35.2%; P less than .001). After adjustment for comorbidities, HCC treatment, race/ethnicity, sex, and age, DAAs were associated with a 39% reduction in risk of death (adjusted hazard ratio, 0.61; 0.53-0.69; P less than .001).
“There were also racial ethnic disparities in patient survival whether patients received DAA or not, with Black patients having worse survival,” Dr. Kam said. “As such, our study highlights that awareness of HCV remains low as does the use of DAA treatment. Therefore, culturally appropriate efforts to improve awareness of HCV must continue among the general public and health care workers as well as efforts to provide point of care accurate and rapid screening tests for HCV so that DAA treatment can be initiated in a timely manner for eligible patients. Continual education on the use of DAA treatment is also needed.”
Robert John Fontana, MD, AGAF, professor of medicine and transplant hepatologist at the University of Michigan, Ann Arbor, described the findings as “frustrating,” and “not the kind of stuff I like to hear about.
“Treatment rates are so low,” Dr. Fontana said, noting that even among gastroenterologists and infectious disease doctors, who should be well-versed in DAAs, antivirals were prescribed less than 30% of the time.
In an interview, Dr. Fontana highlighted the benefits of DAAs, including their ease-of-use and effectiveness.
“Hepatitis C was the leading reason that we had to do liver transplants in the United States for years,” he said. “Then once these really amazing drugs called direct-acting antivirals came out, they changed the landscape very quickly. It really was a game changer for my whole practice, and, nationally, the practice of transplant.”
Yet, this study and others suggest that these practice-altering agents are being underutilized, Dr. Fontana said. A variety of reasons could explain suboptimal usage, he suggested, including lack of awareness among medical professionals and the public, the recency of DAA approvals, low HCV testing rates, lack of symptoms in HCV-positive patients, and medication costs.
This latter barrier, at least, is dissolving, Dr. Fontana said. Some payers initially restricted which providers could prescribe DAAs, but now the economic consensus has swung in their favor, since curing patients of HCV brings significant health care savings down the line. This financial advantage—theoretically multiplied across 4-5 million Americans living with HCV—has bolstered a multi-institutional effort toward universal HCV screening, with testing recommended at least once in every person’s lifetime.
“It’s highly cost effective,” Dr. Fontana said. “Even though the drugs are super expensive, you will reduce cost by preventing the people streaming towards liver cancer or streaming towards liver transplant. That’s why all the professional societies—the USPSTF, the CDC—they all say, ‘OK, screen everyone.’ ”
Screening may be getting easier soon, Dr. Fontana predicted, as at-home HCV-testing kits are on the horizon, with development and adoption likely accelerated by the success of at-home viral testing during the COVID-19 pandemic.
Beyond broader screening, Dr. Fontana suggested that greater awareness of DAAs is needed both within and beyond the medical community.
He advised health care providers who don’t yet feel comfortable diagnosing or treating HCV to refer to their local specialist.
“That’s the main message,” Dr. Fontana said. “I’m always eternally hopeful that every little message helps.”
The investigators and Dr. Fontana disclosed no conflicts of interest.
, and rates aren’t much better for patients seen by specialists, based on a retrospective analysis of private insurance claims.
The study also showed that patients receiving DAAs lived significantly longer, emphasizing the importance of prescribing these medications to all eligible patients, reported principal investigator Mindie H. Nguyen, MD, AGAF,, of Stanford University Medical Center, Palo Alto, California, and colleagues.
“Prior studies have shown evidence of improved survival among HCV-related HCC patients who received DAA treatment, but not much is known about the current DAA utilization among these patients in the general US population,” said lead author Leslie Y. Kam, MD, a postdoctoral scholar in gastroenterology at Stanford Medicine, who presented the findings in November at the annual meeting of the American Association for the Study of Liver Diseases.
To generate real-world data, the investigators analyzed medical records from 3922 patients in Optum’s Clinformatics Data Mart Database. All patients had private medical insurance and received care for HCV-related HCC between 2015 and 2021.
“Instead of using institutional databases which tend to bias toward highly specialized tertiary care center patients, our study uses a large, national sample of HCV-HCC patients that represents real-world DAA treatment rates and survival outcomes,” Dr. Kam said in a written comment.
Within this cohort, fewer than one out of four patients (23.5%) received DAA, a rate that Dr. Kam called “dismally low.”
Patients with either compensated or decompensated cirrhosis had higher treatment rates than those without cirrhosis (24.2% or 24.5%, respectively, vs. 16.2%; P = .001). The investigators noted that more than half of the patients had decompensated cirrhosis, suggesting that HCV-related HCC was diagnosed late in the disease course.
Receiving care from a gastroenterologist or infectious disease physician also was associated with a higher treatment rate. Patients managed by a gastroenterologist alone had a treatment rate of 27.0%, while those who received care from a gastroenterologist or infectious disease doctor alongside an oncologist had a treatment rate of 25.6%, versus just 9.4% for those who received care from an oncologist alone, and 12.4% among those who did not see a specialist of any kind (P = .005).
These findings highlight “the need for a multidisciplinary approach to care in this population,” Dr. Kam suggested.
Echoing previous research, DAAs were associated with extended survival. A significantly greater percentage of patients who received DAA were alive after 5 years, compared with patients who did not receive DAA (47.2% vs. 35.2%; P less than .001). After adjustment for comorbidities, HCC treatment, race/ethnicity, sex, and age, DAAs were associated with a 39% reduction in risk of death (adjusted hazard ratio, 0.61; 0.53-0.69; P less than .001).
“There were also racial ethnic disparities in patient survival whether patients received DAA or not, with Black patients having worse survival,” Dr. Kam said. “As such, our study highlights that awareness of HCV remains low as does the use of DAA treatment. Therefore, culturally appropriate efforts to improve awareness of HCV must continue among the general public and health care workers as well as efforts to provide point of care accurate and rapid screening tests for HCV so that DAA treatment can be initiated in a timely manner for eligible patients. Continual education on the use of DAA treatment is also needed.”
Robert John Fontana, MD, AGAF, professor of medicine and transplant hepatologist at the University of Michigan, Ann Arbor, described the findings as “frustrating,” and “not the kind of stuff I like to hear about.
“Treatment rates are so low,” Dr. Fontana said, noting that even among gastroenterologists and infectious disease doctors, who should be well-versed in DAAs, antivirals were prescribed less than 30% of the time.
In an interview, Dr. Fontana highlighted the benefits of DAAs, including their ease-of-use and effectiveness.
“Hepatitis C was the leading reason that we had to do liver transplants in the United States for years,” he said. “Then once these really amazing drugs called direct-acting antivirals came out, they changed the landscape very quickly. It really was a game changer for my whole practice, and, nationally, the practice of transplant.”
Yet, this study and others suggest that these practice-altering agents are being underutilized, Dr. Fontana said. A variety of reasons could explain suboptimal usage, he suggested, including lack of awareness among medical professionals and the public, the recency of DAA approvals, low HCV testing rates, lack of symptoms in HCV-positive patients, and medication costs.
This latter barrier, at least, is dissolving, Dr. Fontana said. Some payers initially restricted which providers could prescribe DAAs, but now the economic consensus has swung in their favor, since curing patients of HCV brings significant health care savings down the line. This financial advantage—theoretically multiplied across 4-5 million Americans living with HCV—has bolstered a multi-institutional effort toward universal HCV screening, with testing recommended at least once in every person’s lifetime.
“It’s highly cost effective,” Dr. Fontana said. “Even though the drugs are super expensive, you will reduce cost by preventing the people streaming towards liver cancer or streaming towards liver transplant. That’s why all the professional societies—the USPSTF, the CDC—they all say, ‘OK, screen everyone.’ ”
Screening may be getting easier soon, Dr. Fontana predicted, as at-home HCV-testing kits are on the horizon, with development and adoption likely accelerated by the success of at-home viral testing during the COVID-19 pandemic.
Beyond broader screening, Dr. Fontana suggested that greater awareness of DAAs is needed both within and beyond the medical community.
He advised health care providers who don’t yet feel comfortable diagnosing or treating HCV to refer to their local specialist.
“That’s the main message,” Dr. Fontana said. “I’m always eternally hopeful that every little message helps.”
The investigators and Dr. Fontana disclosed no conflicts of interest.
, and rates aren’t much better for patients seen by specialists, based on a retrospective analysis of private insurance claims.
The study also showed that patients receiving DAAs lived significantly longer, emphasizing the importance of prescribing these medications to all eligible patients, reported principal investigator Mindie H. Nguyen, MD, AGAF,, of Stanford University Medical Center, Palo Alto, California, and colleagues.
“Prior studies have shown evidence of improved survival among HCV-related HCC patients who received DAA treatment, but not much is known about the current DAA utilization among these patients in the general US population,” said lead author Leslie Y. Kam, MD, a postdoctoral scholar in gastroenterology at Stanford Medicine, who presented the findings in November at the annual meeting of the American Association for the Study of Liver Diseases.
To generate real-world data, the investigators analyzed medical records from 3922 patients in Optum’s Clinformatics Data Mart Database. All patients had private medical insurance and received care for HCV-related HCC between 2015 and 2021.
“Instead of using institutional databases which tend to bias toward highly specialized tertiary care center patients, our study uses a large, national sample of HCV-HCC patients that represents real-world DAA treatment rates and survival outcomes,” Dr. Kam said in a written comment.
Within this cohort, fewer than one out of four patients (23.5%) received DAA, a rate that Dr. Kam called “dismally low.”
Patients with either compensated or decompensated cirrhosis had higher treatment rates than those without cirrhosis (24.2% or 24.5%, respectively, vs. 16.2%; P = .001). The investigators noted that more than half of the patients had decompensated cirrhosis, suggesting that HCV-related HCC was diagnosed late in the disease course.
Receiving care from a gastroenterologist or infectious disease physician also was associated with a higher treatment rate. Patients managed by a gastroenterologist alone had a treatment rate of 27.0%, while those who received care from a gastroenterologist or infectious disease doctor alongside an oncologist had a treatment rate of 25.6%, versus just 9.4% for those who received care from an oncologist alone, and 12.4% among those who did not see a specialist of any kind (P = .005).
These findings highlight “the need for a multidisciplinary approach to care in this population,” Dr. Kam suggested.
Echoing previous research, DAAs were associated with extended survival. A significantly greater percentage of patients who received DAA were alive after 5 years, compared with patients who did not receive DAA (47.2% vs. 35.2%; P less than .001). After adjustment for comorbidities, HCC treatment, race/ethnicity, sex, and age, DAAs were associated with a 39% reduction in risk of death (adjusted hazard ratio, 0.61; 0.53-0.69; P less than .001).
“There were also racial ethnic disparities in patient survival whether patients received DAA or not, with Black patients having worse survival,” Dr. Kam said. “As such, our study highlights that awareness of HCV remains low as does the use of DAA treatment. Therefore, culturally appropriate efforts to improve awareness of HCV must continue among the general public and health care workers as well as efforts to provide point of care accurate and rapid screening tests for HCV so that DAA treatment can be initiated in a timely manner for eligible patients. Continual education on the use of DAA treatment is also needed.”
Robert John Fontana, MD, AGAF, professor of medicine and transplant hepatologist at the University of Michigan, Ann Arbor, described the findings as “frustrating,” and “not the kind of stuff I like to hear about.
“Treatment rates are so low,” Dr. Fontana said, noting that even among gastroenterologists and infectious disease doctors, who should be well-versed in DAAs, antivirals were prescribed less than 30% of the time.
In an interview, Dr. Fontana highlighted the benefits of DAAs, including their ease-of-use and effectiveness.
“Hepatitis C was the leading reason that we had to do liver transplants in the United States for years,” he said. “Then once these really amazing drugs called direct-acting antivirals came out, they changed the landscape very quickly. It really was a game changer for my whole practice, and, nationally, the practice of transplant.”
Yet, this study and others suggest that these practice-altering agents are being underutilized, Dr. Fontana said. A variety of reasons could explain suboptimal usage, he suggested, including lack of awareness among medical professionals and the public, the recency of DAA approvals, low HCV testing rates, lack of symptoms in HCV-positive patients, and medication costs.
This latter barrier, at least, is dissolving, Dr. Fontana said. Some payers initially restricted which providers could prescribe DAAs, but now the economic consensus has swung in their favor, since curing patients of HCV brings significant health care savings down the line. This financial advantage—theoretically multiplied across 4-5 million Americans living with HCV—has bolstered a multi-institutional effort toward universal HCV screening, with testing recommended at least once in every person’s lifetime.
“It’s highly cost effective,” Dr. Fontana said. “Even though the drugs are super expensive, you will reduce cost by preventing the people streaming towards liver cancer or streaming towards liver transplant. That’s why all the professional societies—the USPSTF, the CDC—they all say, ‘OK, screen everyone.’ ”
Screening may be getting easier soon, Dr. Fontana predicted, as at-home HCV-testing kits are on the horizon, with development and adoption likely accelerated by the success of at-home viral testing during the COVID-19 pandemic.
Beyond broader screening, Dr. Fontana suggested that greater awareness of DAAs is needed both within and beyond the medical community.
He advised health care providers who don’t yet feel comfortable diagnosing or treating HCV to refer to their local specialist.
“That’s the main message,” Dr. Fontana said. “I’m always eternally hopeful that every little message helps.”
The investigators and Dr. Fontana disclosed no conflicts of interest.
AT THE LIVER MEETING
Taste and smell changes linked with worse QOL and cognition in cirrhosis, renal failure
than those who do not exhibit these sensory changes, according to investigators.
Clinicians should screen for changes in taste and smell among patients at risk of cognitive changes, and offer nutritional interventions to support body weight and QOL, reported principal investigator Jasmohan S. Bajaj, MD, AGAF, of Virginia Commonwealth University, Richmond, and colleagues.
“Cirrhosis is linked with poor nutrition, which could partly be due to anorexia in hepatic encephalopathy (HE) and coexistent renal failure,” the investigators wrote in their abstract, which Dr. Bajaj presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“We wanted to measure how changes in the brain in cirrhosis affect patients’ abilities to smell and taste, and study how that affects their quality of life,” Dr. Bajaj said in a written comment.
To this end, the investigators conducted an observational study involving 59 participants, among whom 22 were healthy, 21 had cirrhosis, and 16 had renal failure requiring dialysis.
“Prior studies individually have shown changes in taste and smell for these two organ failures,” Dr. Bajaj said. “We studied them together as well and linked these to quality of life and individual cognitive tests.”
Of note, individuals with past or current COVID-19, or with current or recent alcohol or tobacco use, were excluded.
Compared with healthy individuals, participants with cirrhosis or renal failure had significantly worse performance on a taste discrimination test, with perceptions of sweet and sour most affected.
Cognitive measurement with Psychometric Hepatic Encephalopathy Score (PHES) and Stroop tests showed that scores were worse for patients with disease than those without. Taste discrimination significantly correlated with both cognitive test scores, regardless of HE or dialysis, whereas smell only correlated with the Stroop test.
Multivariable analysis revealed that better PHES scores and smell discrimination were linked with better taste discrimination. Similarly, better PHES scores and taste discrimination contributed to better smell discrimination. Eating impairment was associated with worse Stroop scores and worse olfactory-related QOL, suggesting that sensory changes, cognitive changes, and eating behaviors were all correlated.
“Health care providers ought to be alert to changes in patients’ eating habits, diet and weight as their liver and kidney disease worsen and as their brain function changes,” Dr. Bajaj said. “Nutritionists and others may be able to assist patients with a healthy diet and suggest ways to improve patients’ reports of their quality of life. Taste and smell are just a few aspects of the complicated assessment of health-related quality of life, brain dysfunction, and nutritional compromise in cirrhosis. We need to be mindful to not just focus on these aspects but to individualize care.”
Adrian M. Di Bisceglie, MD, hepatologist and emeritus professor of internal medicine at Saint Louis University, said the study was “well done,” and called the findings “an interesting little tidbit” that would probably not change his practice as a physician, but could be valuable for designing nutritional interventions.
In an interview, Dr. Di Bisceglie explained that a well-balanced diet with adequate caloric intake can help slow the muscle wasting that occurs with the condition, but creating a tasty menu can be challenging when patients are asked to restrict their sodium intake as a means of reducing fluid retention.
“Salt contributes substantially to the enjoyment of food,” Dr. Di Bisceglie said.
Although the study did not specifically report the salt level in patients’ diets, Dr. Di Bisceglie said the findings highlight the need for low-salt strategies to improve palatability. For example, he suggested increasing umami, or savory flavor, as this can be accomplished without adding a significant amount of salt.
When asked if changes in taste or smell might be used as simple screening tools to detect cognitive impairment in patients with cirrhosis, Dr. Di Bisceglie said that this might be “possible,” but is probably unnecessary.
“There is an easy bedside test that we’ve been using for decades [to predict hepatic encephalopathy], which is reading,” Dr. Di Bisceglie said, noting that patients with cognitive deficits often describe reading paragraphs repeatedly without comprehending what they have read.
The investigators and Dr. Di Bisceglie disclosed no conflicts of interest.
than those who do not exhibit these sensory changes, according to investigators.
Clinicians should screen for changes in taste and smell among patients at risk of cognitive changes, and offer nutritional interventions to support body weight and QOL, reported principal investigator Jasmohan S. Bajaj, MD, AGAF, of Virginia Commonwealth University, Richmond, and colleagues.
“Cirrhosis is linked with poor nutrition, which could partly be due to anorexia in hepatic encephalopathy (HE) and coexistent renal failure,” the investigators wrote in their abstract, which Dr. Bajaj presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“We wanted to measure how changes in the brain in cirrhosis affect patients’ abilities to smell and taste, and study how that affects their quality of life,” Dr. Bajaj said in a written comment.
To this end, the investigators conducted an observational study involving 59 participants, among whom 22 were healthy, 21 had cirrhosis, and 16 had renal failure requiring dialysis.
“Prior studies individually have shown changes in taste and smell for these two organ failures,” Dr. Bajaj said. “We studied them together as well and linked these to quality of life and individual cognitive tests.”
Of note, individuals with past or current COVID-19, or with current or recent alcohol or tobacco use, were excluded.
Compared with healthy individuals, participants with cirrhosis or renal failure had significantly worse performance on a taste discrimination test, with perceptions of sweet and sour most affected.
Cognitive measurement with Psychometric Hepatic Encephalopathy Score (PHES) and Stroop tests showed that scores were worse for patients with disease than those without. Taste discrimination significantly correlated with both cognitive test scores, regardless of HE or dialysis, whereas smell only correlated with the Stroop test.
Multivariable analysis revealed that better PHES scores and smell discrimination were linked with better taste discrimination. Similarly, better PHES scores and taste discrimination contributed to better smell discrimination. Eating impairment was associated with worse Stroop scores and worse olfactory-related QOL, suggesting that sensory changes, cognitive changes, and eating behaviors were all correlated.
“Health care providers ought to be alert to changes in patients’ eating habits, diet and weight as their liver and kidney disease worsen and as their brain function changes,” Dr. Bajaj said. “Nutritionists and others may be able to assist patients with a healthy diet and suggest ways to improve patients’ reports of their quality of life. Taste and smell are just a few aspects of the complicated assessment of health-related quality of life, brain dysfunction, and nutritional compromise in cirrhosis. We need to be mindful to not just focus on these aspects but to individualize care.”
Adrian M. Di Bisceglie, MD, hepatologist and emeritus professor of internal medicine at Saint Louis University, said the study was “well done,” and called the findings “an interesting little tidbit” that would probably not change his practice as a physician, but could be valuable for designing nutritional interventions.
In an interview, Dr. Di Bisceglie explained that a well-balanced diet with adequate caloric intake can help slow the muscle wasting that occurs with the condition, but creating a tasty menu can be challenging when patients are asked to restrict their sodium intake as a means of reducing fluid retention.
“Salt contributes substantially to the enjoyment of food,” Dr. Di Bisceglie said.
Although the study did not specifically report the salt level in patients’ diets, Dr. Di Bisceglie said the findings highlight the need for low-salt strategies to improve palatability. For example, he suggested increasing umami, or savory flavor, as this can be accomplished without adding a significant amount of salt.
When asked if changes in taste or smell might be used as simple screening tools to detect cognitive impairment in patients with cirrhosis, Dr. Di Bisceglie said that this might be “possible,” but is probably unnecessary.
“There is an easy bedside test that we’ve been using for decades [to predict hepatic encephalopathy], which is reading,” Dr. Di Bisceglie said, noting that patients with cognitive deficits often describe reading paragraphs repeatedly without comprehending what they have read.
The investigators and Dr. Di Bisceglie disclosed no conflicts of interest.
than those who do not exhibit these sensory changes, according to investigators.
Clinicians should screen for changes in taste and smell among patients at risk of cognitive changes, and offer nutritional interventions to support body weight and QOL, reported principal investigator Jasmohan S. Bajaj, MD, AGAF, of Virginia Commonwealth University, Richmond, and colleagues.
“Cirrhosis is linked with poor nutrition, which could partly be due to anorexia in hepatic encephalopathy (HE) and coexistent renal failure,” the investigators wrote in their abstract, which Dr. Bajaj presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“We wanted to measure how changes in the brain in cirrhosis affect patients’ abilities to smell and taste, and study how that affects their quality of life,” Dr. Bajaj said in a written comment.
To this end, the investigators conducted an observational study involving 59 participants, among whom 22 were healthy, 21 had cirrhosis, and 16 had renal failure requiring dialysis.
“Prior studies individually have shown changes in taste and smell for these two organ failures,” Dr. Bajaj said. “We studied them together as well and linked these to quality of life and individual cognitive tests.”
Of note, individuals with past or current COVID-19, or with current or recent alcohol or tobacco use, were excluded.
Compared with healthy individuals, participants with cirrhosis or renal failure had significantly worse performance on a taste discrimination test, with perceptions of sweet and sour most affected.
Cognitive measurement with Psychometric Hepatic Encephalopathy Score (PHES) and Stroop tests showed that scores were worse for patients with disease than those without. Taste discrimination significantly correlated with both cognitive test scores, regardless of HE or dialysis, whereas smell only correlated with the Stroop test.
Multivariable analysis revealed that better PHES scores and smell discrimination were linked with better taste discrimination. Similarly, better PHES scores and taste discrimination contributed to better smell discrimination. Eating impairment was associated with worse Stroop scores and worse olfactory-related QOL, suggesting that sensory changes, cognitive changes, and eating behaviors were all correlated.
“Health care providers ought to be alert to changes in patients’ eating habits, diet and weight as their liver and kidney disease worsen and as their brain function changes,” Dr. Bajaj said. “Nutritionists and others may be able to assist patients with a healthy diet and suggest ways to improve patients’ reports of their quality of life. Taste and smell are just a few aspects of the complicated assessment of health-related quality of life, brain dysfunction, and nutritional compromise in cirrhosis. We need to be mindful to not just focus on these aspects but to individualize care.”
Adrian M. Di Bisceglie, MD, hepatologist and emeritus professor of internal medicine at Saint Louis University, said the study was “well done,” and called the findings “an interesting little tidbit” that would probably not change his practice as a physician, but could be valuable for designing nutritional interventions.
In an interview, Dr. Di Bisceglie explained that a well-balanced diet with adequate caloric intake can help slow the muscle wasting that occurs with the condition, but creating a tasty menu can be challenging when patients are asked to restrict their sodium intake as a means of reducing fluid retention.
“Salt contributes substantially to the enjoyment of food,” Dr. Di Bisceglie said.
Although the study did not specifically report the salt level in patients’ diets, Dr. Di Bisceglie said the findings highlight the need for low-salt strategies to improve palatability. For example, he suggested increasing umami, or savory flavor, as this can be accomplished without adding a significant amount of salt.
When asked if changes in taste or smell might be used as simple screening tools to detect cognitive impairment in patients with cirrhosis, Dr. Di Bisceglie said that this might be “possible,” but is probably unnecessary.
“There is an easy bedside test that we’ve been using for decades [to predict hepatic encephalopathy], which is reading,” Dr. Di Bisceglie said, noting that patients with cognitive deficits often describe reading paragraphs repeatedly without comprehending what they have read.
The investigators and Dr. Di Bisceglie disclosed no conflicts of interest.
AT THE LIVER MEETING
Is fructose all to blame for obesity?
A recent article hypothesized that fructose causes more metabolic disease than does sucrose when overfed in the human diet. Fructose intake as high-fructose corn syrup (HFCS) has risen since its use in soft drinks in the United States and parallels the increase in the prevalence of obesity.
The newest hypothesis regarding fructose invokes a genetic survival of the fittest rationale for how fructose-enhanced fat deposition exacerbates the increased caloric consumption from the Western diet to promote metabolic disease especially in our adolescent and young adult population. This theory suggests that fructose consumption causes low adenosine triphosphate, which stimulates energy intake causing an imbalance of energy regulation.
Ongoing interest in the association between the increased use of HFCS and the prevalence of obesity in the United States continues. The use of HFCS in sugary sweetened beverages (SSBs) has reduced the cost of these beverages because of technology in preparing HFCS from corn and the substitution of the cheaper HFCS for sugar in SSBs. Although SSBs haven’t been proven to cause obesity, there has been an increase in the risk for type 2 diabetes, cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and even cancer. Research in HFCS, weight gain, and metabolic disease continues despite little definitive evidence of causation.
The relationship between SSBs consumption and obesity has been attributed to the increase in overall total caloric intake of the diet. These liquid calories do not suppress the intake of other foods to equalize the total amount of calories ingested. This knowledge has been gleaned from work performed by R. Mattes and B. Rolls in the 1990s through the early 2000s.
This research and the current work on HFCS and metabolic disease is important because there are adolescents and young adults in the United States and globally that ingest a large amount of SSBs and therefore are at risk for metabolic disease, type 2 diabetes, NAFLD, and CVD at an early age.
, around 1970-1980.
Researchers noted the association and began to focus on potential reasons to pinpoint HFCS or fructose itself so we have a mechanism of action specific to fructose. Therefore, the public could be warned about the risk of drinking SSBs due to the HFCS and fructose ingested and the possibility of metabolic disease. Perhaps, there is a method to remove harmful HFCS from the food supply much like what has happened with industrially produced trans fatty acids. In 2018, the World Health Organization called for a total ban on trans fats due to causation of 500 million early deaths per year globally.
Similar to the process of making HFCS, most trans fats are formed through an industrial process that alters vegetable oil and creates a shelf stable inexpensive partially hydrogenated oil. Trans fats have been shown to increase low-density lipoprotein (LDL) cholesterol and decrease high-density lipoprotein (HDL) increasing the risk for myocardial infarction and stroke.
What was the pivotal moment for the ban on trans fats? It was tough convincing the scientific community and certainly the industry that trans fats were especially harmful. This is because of the dogma that margarine and Crisco oils were somehow better for you than were lard and butter. The evidence kept coming in from epidemiological studies showing that people who ate more trans fats had increased levels of LDL and decreased levels of HDL, and the dogma that saturated fat was the villain in heart disease was reinforced. Maybe that pivotal moment was when a researcher with experience testing trans fat deposition in cadavers and pigs sued the US Food and Drug Administration (FDA) for not acting on cumulative evidence sooner.
Do we have this kind of evidence to make a claim for the FDA to ban HFCS? What we have is the time course of HFCS entry into the food supply which occurred in 1970. This coincided with the growing prevalence of obesity between 1960 and 2000.
The excess energy in SSBs can provide a hedonic stimulus that overcomes the natural energy balance regulatory mechanism because SSBs excess energy comes in liquid form and may bypass the satiety signal in the hypothalamus.
We still have to prove this.
Blaming fructose in HFCS as the sole cause for the increase obesity will be much tougher than blaming trans fats for an increase in LDL cholesterol and a decrease in HDL cholesterol.
The prevalence of obesity has increased worldwide, even in countries where SSBs do not contain HFCS.
Still, the proof that HFCS can override the satiety pathway and cause excess calorie intake is intriguing and may have teeth if we can pinpoint the increase in prevalence of obesity in children and adolescents on increased ingestion of HFCS in SSBs. There is no reason nutritionally to add sugar or HFCS to liquids. Plus, if HFCS has a metabolic disadvantage then all the more reason to ban it. Then, it becomes like trans fats: a toxin in the food supply.
Dr. Apovian is a Faculty Member, Department of Medicine; Co-Director, Center for Weight Management and Wellness, Section of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. She has disclosed financial relationships with Altimmune, Inc; Cowen and Company, LLC; Currax Pharmaceuticals, LLC; EPG Communication Holdings, Ltd; Gelesis, Srl; L-Nutra, Inc; NeuroBo Pharmaceuticals; and Novo Nordisk, Inc. She has received research grants from the National Institutes of Health; Patient-Centered Outcomes Research Institute; GI Dynamics, Inc.
A version of this article appeared on Medscape.com.
A recent article hypothesized that fructose causes more metabolic disease than does sucrose when overfed in the human diet. Fructose intake as high-fructose corn syrup (HFCS) has risen since its use in soft drinks in the United States and parallels the increase in the prevalence of obesity.
The newest hypothesis regarding fructose invokes a genetic survival of the fittest rationale for how fructose-enhanced fat deposition exacerbates the increased caloric consumption from the Western diet to promote metabolic disease especially in our adolescent and young adult population. This theory suggests that fructose consumption causes low adenosine triphosphate, which stimulates energy intake causing an imbalance of energy regulation.
Ongoing interest in the association between the increased use of HFCS and the prevalence of obesity in the United States continues. The use of HFCS in sugary sweetened beverages (SSBs) has reduced the cost of these beverages because of technology in preparing HFCS from corn and the substitution of the cheaper HFCS for sugar in SSBs. Although SSBs haven’t been proven to cause obesity, there has been an increase in the risk for type 2 diabetes, cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and even cancer. Research in HFCS, weight gain, and metabolic disease continues despite little definitive evidence of causation.
The relationship between SSBs consumption and obesity has been attributed to the increase in overall total caloric intake of the diet. These liquid calories do not suppress the intake of other foods to equalize the total amount of calories ingested. This knowledge has been gleaned from work performed by R. Mattes and B. Rolls in the 1990s through the early 2000s.
This research and the current work on HFCS and metabolic disease is important because there are adolescents and young adults in the United States and globally that ingest a large amount of SSBs and therefore are at risk for metabolic disease, type 2 diabetes, NAFLD, and CVD at an early age.
, around 1970-1980.
Researchers noted the association and began to focus on potential reasons to pinpoint HFCS or fructose itself so we have a mechanism of action specific to fructose. Therefore, the public could be warned about the risk of drinking SSBs due to the HFCS and fructose ingested and the possibility of metabolic disease. Perhaps, there is a method to remove harmful HFCS from the food supply much like what has happened with industrially produced trans fatty acids. In 2018, the World Health Organization called for a total ban on trans fats due to causation of 500 million early deaths per year globally.
Similar to the process of making HFCS, most trans fats are formed through an industrial process that alters vegetable oil and creates a shelf stable inexpensive partially hydrogenated oil. Trans fats have been shown to increase low-density lipoprotein (LDL) cholesterol and decrease high-density lipoprotein (HDL) increasing the risk for myocardial infarction and stroke.
What was the pivotal moment for the ban on trans fats? It was tough convincing the scientific community and certainly the industry that trans fats were especially harmful. This is because of the dogma that margarine and Crisco oils were somehow better for you than were lard and butter. The evidence kept coming in from epidemiological studies showing that people who ate more trans fats had increased levels of LDL and decreased levels of HDL, and the dogma that saturated fat was the villain in heart disease was reinforced. Maybe that pivotal moment was when a researcher with experience testing trans fat deposition in cadavers and pigs sued the US Food and Drug Administration (FDA) for not acting on cumulative evidence sooner.
Do we have this kind of evidence to make a claim for the FDA to ban HFCS? What we have is the time course of HFCS entry into the food supply which occurred in 1970. This coincided with the growing prevalence of obesity between 1960 and 2000.
The excess energy in SSBs can provide a hedonic stimulus that overcomes the natural energy balance regulatory mechanism because SSBs excess energy comes in liquid form and may bypass the satiety signal in the hypothalamus.
We still have to prove this.
Blaming fructose in HFCS as the sole cause for the increase obesity will be much tougher than blaming trans fats for an increase in LDL cholesterol and a decrease in HDL cholesterol.
The prevalence of obesity has increased worldwide, even in countries where SSBs do not contain HFCS.
Still, the proof that HFCS can override the satiety pathway and cause excess calorie intake is intriguing and may have teeth if we can pinpoint the increase in prevalence of obesity in children and adolescents on increased ingestion of HFCS in SSBs. There is no reason nutritionally to add sugar or HFCS to liquids. Plus, if HFCS has a metabolic disadvantage then all the more reason to ban it. Then, it becomes like trans fats: a toxin in the food supply.
Dr. Apovian is a Faculty Member, Department of Medicine; Co-Director, Center for Weight Management and Wellness, Section of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. She has disclosed financial relationships with Altimmune, Inc; Cowen and Company, LLC; Currax Pharmaceuticals, LLC; EPG Communication Holdings, Ltd; Gelesis, Srl; L-Nutra, Inc; NeuroBo Pharmaceuticals; and Novo Nordisk, Inc. She has received research grants from the National Institutes of Health; Patient-Centered Outcomes Research Institute; GI Dynamics, Inc.
A version of this article appeared on Medscape.com.
A recent article hypothesized that fructose causes more metabolic disease than does sucrose when overfed in the human diet. Fructose intake as high-fructose corn syrup (HFCS) has risen since its use in soft drinks in the United States and parallels the increase in the prevalence of obesity.
The newest hypothesis regarding fructose invokes a genetic survival of the fittest rationale for how fructose-enhanced fat deposition exacerbates the increased caloric consumption from the Western diet to promote metabolic disease especially in our adolescent and young adult population. This theory suggests that fructose consumption causes low adenosine triphosphate, which stimulates energy intake causing an imbalance of energy regulation.
Ongoing interest in the association between the increased use of HFCS and the prevalence of obesity in the United States continues. The use of HFCS in sugary sweetened beverages (SSBs) has reduced the cost of these beverages because of technology in preparing HFCS from corn and the substitution of the cheaper HFCS for sugar in SSBs. Although SSBs haven’t been proven to cause obesity, there has been an increase in the risk for type 2 diabetes, cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and even cancer. Research in HFCS, weight gain, and metabolic disease continues despite little definitive evidence of causation.
The relationship between SSBs consumption and obesity has been attributed to the increase in overall total caloric intake of the diet. These liquid calories do not suppress the intake of other foods to equalize the total amount of calories ingested. This knowledge has been gleaned from work performed by R. Mattes and B. Rolls in the 1990s through the early 2000s.
This research and the current work on HFCS and metabolic disease is important because there are adolescents and young adults in the United States and globally that ingest a large amount of SSBs and therefore are at risk for metabolic disease, type 2 diabetes, NAFLD, and CVD at an early age.
, around 1970-1980.
Researchers noted the association and began to focus on potential reasons to pinpoint HFCS or fructose itself so we have a mechanism of action specific to fructose. Therefore, the public could be warned about the risk of drinking SSBs due to the HFCS and fructose ingested and the possibility of metabolic disease. Perhaps, there is a method to remove harmful HFCS from the food supply much like what has happened with industrially produced trans fatty acids. In 2018, the World Health Organization called for a total ban on trans fats due to causation of 500 million early deaths per year globally.
Similar to the process of making HFCS, most trans fats are formed through an industrial process that alters vegetable oil and creates a shelf stable inexpensive partially hydrogenated oil. Trans fats have been shown to increase low-density lipoprotein (LDL) cholesterol and decrease high-density lipoprotein (HDL) increasing the risk for myocardial infarction and stroke.
What was the pivotal moment for the ban on trans fats? It was tough convincing the scientific community and certainly the industry that trans fats were especially harmful. This is because of the dogma that margarine and Crisco oils were somehow better for you than were lard and butter. The evidence kept coming in from epidemiological studies showing that people who ate more trans fats had increased levels of LDL and decreased levels of HDL, and the dogma that saturated fat was the villain in heart disease was reinforced. Maybe that pivotal moment was when a researcher with experience testing trans fat deposition in cadavers and pigs sued the US Food and Drug Administration (FDA) for not acting on cumulative evidence sooner.
Do we have this kind of evidence to make a claim for the FDA to ban HFCS? What we have is the time course of HFCS entry into the food supply which occurred in 1970. This coincided with the growing prevalence of obesity between 1960 and 2000.
The excess energy in SSBs can provide a hedonic stimulus that overcomes the natural energy balance regulatory mechanism because SSBs excess energy comes in liquid form and may bypass the satiety signal in the hypothalamus.
We still have to prove this.
Blaming fructose in HFCS as the sole cause for the increase obesity will be much tougher than blaming trans fats for an increase in LDL cholesterol and a decrease in HDL cholesterol.
The prevalence of obesity has increased worldwide, even in countries where SSBs do not contain HFCS.
Still, the proof that HFCS can override the satiety pathway and cause excess calorie intake is intriguing and may have teeth if we can pinpoint the increase in prevalence of obesity in children and adolescents on increased ingestion of HFCS in SSBs. There is no reason nutritionally to add sugar or HFCS to liquids. Plus, if HFCS has a metabolic disadvantage then all the more reason to ban it. Then, it becomes like trans fats: a toxin in the food supply.
Dr. Apovian is a Faculty Member, Department of Medicine; Co-Director, Center for Weight Management and Wellness, Section of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. She has disclosed financial relationships with Altimmune, Inc; Cowen and Company, LLC; Currax Pharmaceuticals, LLC; EPG Communication Holdings, Ltd; Gelesis, Srl; L-Nutra, Inc; NeuroBo Pharmaceuticals; and Novo Nordisk, Inc. She has received research grants from the National Institutes of Health; Patient-Centered Outcomes Research Institute; GI Dynamics, Inc.
A version of this article appeared on Medscape.com.
COVID livers are safe for transplant
, based on a national study with the longest follow-up to date.
Using livers from deceased patients with COVID-19 could be an opportunity expand organ availability, reported principal investigator Nadim Mahmud, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
Findings were presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“During the COVID-19 pandemic, a few centers trialed transplanting solid organs from COVID-19 positive donors with promising initial results,” presenting author Roy X. Wang, MD, of the University of Pennsylvania, said in a written comment. “However, these were smaller experiences with short follow-up that were not exclusively focused on liver transplantation. We wanted to explore the safety of liver transplantation from COVID-19 positive donors using a large national dataset with the longest follow up time to date.”
The dataset included 13,096 COVID-negative donors and 299 COVID-positive donors who died between July 2020 and July 2022, with cases and controls matched via propensity scoring. COVID-positive donors were significantly more likely to be younger and have died of brain death. Beyond this difference in age, no significant demographic differences were detected.
After 1 year of follow-up, no statistically significant differences in patient survival (subhazard ratio, 1.11; log-rank P = .70) or allograft survival (hazard ratio, 1.44; log-rank P = .14) were detected when comparing livers transplanted from positive versus negative donors.
“Our findings support and expand upon the results from earlier studies,” Dr. Wang concluded. “Liver transplant from COVID-19-positive donors has acceptable short-term outcomes and may represent an opportunity to expand organ access.”
Still, more work is needed to assess other clinical metrics and long-term outcomes, he added.
“While we were able to show similar patient and graft survival post-transplant between COVID-19-positive and negative donors, rates of other complications were not investigated such as episodes of rejection, liver injury, and hospitalizations,” Dr. Wang said. “Due to data limitations, we are only able to report on outcomes up to 1 year post transplant. Additional investigation will be needed to continue monitoring future outcomes and identifying any differences between recipients of COVID-19-positive and negative donors.”
Timucin Taner, MD, PhD, division chair of transplant surgery at Mayo Clinic, Rochester, Minnesota, said the study is important because it reaffirms the majority opinion among transplant physicians: These livers are safe.
In an interview, Dr. Taner suggested that Dr. Wang’s call for longer term data is “mostly science speak,” since 1 year of follow-up should be sufficient to determine liver viability.
“If a liver from a COVID-19 donor behaved well for a year, then chances are it’s not going to behave badly [later on] because of the virus at the time of donation,” Dr. Taner said.
He said the reported trends in usage of COVID-positive livers reflect early hesitancy that waned with rising vaccination rates, and recognition that the virus could not be spread via liver donation.
“To date, the only transmission [of SARS-CoV-2] from a transplant has been from a lung transplant,” Dr. Taner said, “and that was back in the days that we didn’t know about this. Other organs don’t transmit the disease, so they are easily usable.”
These new data should further increase confidence among both health care providers and patients, he added.
“[This study is] reassuring to the patients on the waitlist that these organs are very safe to use,” Dr. Taner said. “We as the transplant society are comfortable using them without any hesitation.”
The investigators and Dr. Taner disclosed no conflicts of interest.
, based on a national study with the longest follow-up to date.
Using livers from deceased patients with COVID-19 could be an opportunity expand organ availability, reported principal investigator Nadim Mahmud, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
Findings were presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“During the COVID-19 pandemic, a few centers trialed transplanting solid organs from COVID-19 positive donors with promising initial results,” presenting author Roy X. Wang, MD, of the University of Pennsylvania, said in a written comment. “However, these were smaller experiences with short follow-up that were not exclusively focused on liver transplantation. We wanted to explore the safety of liver transplantation from COVID-19 positive donors using a large national dataset with the longest follow up time to date.”
The dataset included 13,096 COVID-negative donors and 299 COVID-positive donors who died between July 2020 and July 2022, with cases and controls matched via propensity scoring. COVID-positive donors were significantly more likely to be younger and have died of brain death. Beyond this difference in age, no significant demographic differences were detected.
After 1 year of follow-up, no statistically significant differences in patient survival (subhazard ratio, 1.11; log-rank P = .70) or allograft survival (hazard ratio, 1.44; log-rank P = .14) were detected when comparing livers transplanted from positive versus negative donors.
“Our findings support and expand upon the results from earlier studies,” Dr. Wang concluded. “Liver transplant from COVID-19-positive donors has acceptable short-term outcomes and may represent an opportunity to expand organ access.”
Still, more work is needed to assess other clinical metrics and long-term outcomes, he added.
“While we were able to show similar patient and graft survival post-transplant between COVID-19-positive and negative donors, rates of other complications were not investigated such as episodes of rejection, liver injury, and hospitalizations,” Dr. Wang said. “Due to data limitations, we are only able to report on outcomes up to 1 year post transplant. Additional investigation will be needed to continue monitoring future outcomes and identifying any differences between recipients of COVID-19-positive and negative donors.”
Timucin Taner, MD, PhD, division chair of transplant surgery at Mayo Clinic, Rochester, Minnesota, said the study is important because it reaffirms the majority opinion among transplant physicians: These livers are safe.
In an interview, Dr. Taner suggested that Dr. Wang’s call for longer term data is “mostly science speak,” since 1 year of follow-up should be sufficient to determine liver viability.
“If a liver from a COVID-19 donor behaved well for a year, then chances are it’s not going to behave badly [later on] because of the virus at the time of donation,” Dr. Taner said.
He said the reported trends in usage of COVID-positive livers reflect early hesitancy that waned with rising vaccination rates, and recognition that the virus could not be spread via liver donation.
“To date, the only transmission [of SARS-CoV-2] from a transplant has been from a lung transplant,” Dr. Taner said, “and that was back in the days that we didn’t know about this. Other organs don’t transmit the disease, so they are easily usable.”
These new data should further increase confidence among both health care providers and patients, he added.
“[This study is] reassuring to the patients on the waitlist that these organs are very safe to use,” Dr. Taner said. “We as the transplant society are comfortable using them without any hesitation.”
The investigators and Dr. Taner disclosed no conflicts of interest.
, based on a national study with the longest follow-up to date.
Using livers from deceased patients with COVID-19 could be an opportunity expand organ availability, reported principal investigator Nadim Mahmud, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
Findings were presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“During the COVID-19 pandemic, a few centers trialed transplanting solid organs from COVID-19 positive donors with promising initial results,” presenting author Roy X. Wang, MD, of the University of Pennsylvania, said in a written comment. “However, these were smaller experiences with short follow-up that were not exclusively focused on liver transplantation. We wanted to explore the safety of liver transplantation from COVID-19 positive donors using a large national dataset with the longest follow up time to date.”
The dataset included 13,096 COVID-negative donors and 299 COVID-positive donors who died between July 2020 and July 2022, with cases and controls matched via propensity scoring. COVID-positive donors were significantly more likely to be younger and have died of brain death. Beyond this difference in age, no significant demographic differences were detected.
After 1 year of follow-up, no statistically significant differences in patient survival (subhazard ratio, 1.11; log-rank P = .70) or allograft survival (hazard ratio, 1.44; log-rank P = .14) were detected when comparing livers transplanted from positive versus negative donors.
“Our findings support and expand upon the results from earlier studies,” Dr. Wang concluded. “Liver transplant from COVID-19-positive donors has acceptable short-term outcomes and may represent an opportunity to expand organ access.”
Still, more work is needed to assess other clinical metrics and long-term outcomes, he added.
“While we were able to show similar patient and graft survival post-transplant between COVID-19-positive and negative donors, rates of other complications were not investigated such as episodes of rejection, liver injury, and hospitalizations,” Dr. Wang said. “Due to data limitations, we are only able to report on outcomes up to 1 year post transplant. Additional investigation will be needed to continue monitoring future outcomes and identifying any differences between recipients of COVID-19-positive and negative donors.”
Timucin Taner, MD, PhD, division chair of transplant surgery at Mayo Clinic, Rochester, Minnesota, said the study is important because it reaffirms the majority opinion among transplant physicians: These livers are safe.
In an interview, Dr. Taner suggested that Dr. Wang’s call for longer term data is “mostly science speak,” since 1 year of follow-up should be sufficient to determine liver viability.
“If a liver from a COVID-19 donor behaved well for a year, then chances are it’s not going to behave badly [later on] because of the virus at the time of donation,” Dr. Taner said.
He said the reported trends in usage of COVID-positive livers reflect early hesitancy that waned with rising vaccination rates, and recognition that the virus could not be spread via liver donation.
“To date, the only transmission [of SARS-CoV-2] from a transplant has been from a lung transplant,” Dr. Taner said, “and that was back in the days that we didn’t know about this. Other organs don’t transmit the disease, so they are easily usable.”
These new data should further increase confidence among both health care providers and patients, he added.
“[This study is] reassuring to the patients on the waitlist that these organs are very safe to use,” Dr. Taner said. “We as the transplant society are comfortable using them without any hesitation.”
The investigators and Dr. Taner disclosed no conflicts of interest.
AT THE LIVER MEETING
More than one-third of adults in the US could have NAFLD by 2050
, according to investigators.
These findings suggest that health care systems should prepare for “large increases” in cases of hepatocellular carcinoma (HCC) and need for liver transplants, reported lead author Phuc Le, PhD, MPH, of the Cleveland Clinic, and colleagues.
“Following the alarming rise in prevalence of obesity and diabetes, NAFLD is projected to become the leading indication for liver transplant in the United States in the next decade,” Dr. Le and colleagues wrote in their abstract for the annual meeting of the American Association for the Study of Liver Diseases. “A better understanding of the clinical burden associated with NAFLD will enable health systems to prepare to meet this imminent demand from patients.”
To this end, Dr. Le and colleagues developed an agent-based state transition model to predict future prevalence of NAFLD and associated outcomes.
In the first part of the model, the investigators simulated population growth in the United States using Census Bureau data, including new births and immigration, from the year 2000 onward. The second part of the model simulated natural progression of NAFLD in adults via 14 associated conditions and events, including steatosis, nonalcoholic steatohepatitis (NASH), HCC, liver transplants, liver-related mortality, and others.
By first comparing simulated findings with actual findings between 2000 and 2018, the investigators confirmed that their model could reliably predict the intended epidemiological parameters.
Next, they turned their model toward the future.
It predicted that the prevalence of NAFLD among US adults will rise from 27.8% in 2020 to 34.3% in 2050. Over the same timeframe, prevalence of NASH is predicted to increase from 20.0% to 21.8%, proportion of NAFLD cases developing cirrhosis is expected to increase from 1.9% to 3.1%, and liver-related mortality is estimated to rise from 0.4% to 1% of all deaths.
The model also predicted that the burden of HCC will increase from 10,400 to 19,300 new cases per year, while liver transplant burden will more than double, from 1,700 to 4,200 transplants per year.
“Our model forecasts substantial clinical burden of NAFLD over the next three decades,” Dr. Le said in a virtual press conference. “And in the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant.”
During the press conference, Norah Terrault, MD, president of the AASLD from the University of Southern California, Los Angeles, noted that all of the reported outcomes, including increasing rates of liver cancer, cirrhosis, and transplants are “potentially preventable.”
Dr. Terrault went on to suggest ways of combating this increasing burden of NAFLD, which she referred to as metabolic dysfunction–associated steatotic liver disease (MASLD), the name now recommended by the AASLD.
“There’s no way we’re going to be able to transplant our way out of this,” Dr. Terrault said. “We need to be bringing greater awareness both to patients, as well as to providers about how we seek out the diagnosis. And we need to bring greater awareness to the population around the things that contribute to MASLD.”
Rates of obesity and diabetes continue to rise, Dr. Terrault said, explaining why MASLD is more common than ever. To counteract these trends, she called for greater awareness of driving factors, such as dietary choices and sedentary lifestyle.
“These are all really important messages that we want to get out to the population, and are really the cornerstones for how we approach the management of patients who have MASLD,” Dr. Terrault said.
In discussion with Dr. Terrault, Dr. Le agreed that increased education may help stem the rising tide of disease, while treatment advances could also increase the odds of a brighter future.
“If we improve our management of NAFLD, or NAFLD-related comorbidities, and if we can develop an effective treatment for NAFLD, then obviously the future would not be so dark,” Dr. Le said, noting promising phase 3 data that would be presented at the meeting. “We are hopeful that the future of disease burden will not be as bad as our model predicts.”
The study was funded by the Agency for Healthcare Research and Quality. The investigators disclosed no conflicts of interest.
, according to investigators.
These findings suggest that health care systems should prepare for “large increases” in cases of hepatocellular carcinoma (HCC) and need for liver transplants, reported lead author Phuc Le, PhD, MPH, of the Cleveland Clinic, and colleagues.
“Following the alarming rise in prevalence of obesity and diabetes, NAFLD is projected to become the leading indication for liver transplant in the United States in the next decade,” Dr. Le and colleagues wrote in their abstract for the annual meeting of the American Association for the Study of Liver Diseases. “A better understanding of the clinical burden associated with NAFLD will enable health systems to prepare to meet this imminent demand from patients.”
To this end, Dr. Le and colleagues developed an agent-based state transition model to predict future prevalence of NAFLD and associated outcomes.
In the first part of the model, the investigators simulated population growth in the United States using Census Bureau data, including new births and immigration, from the year 2000 onward. The second part of the model simulated natural progression of NAFLD in adults via 14 associated conditions and events, including steatosis, nonalcoholic steatohepatitis (NASH), HCC, liver transplants, liver-related mortality, and others.
By first comparing simulated findings with actual findings between 2000 and 2018, the investigators confirmed that their model could reliably predict the intended epidemiological parameters.
Next, they turned their model toward the future.
It predicted that the prevalence of NAFLD among US adults will rise from 27.8% in 2020 to 34.3% in 2050. Over the same timeframe, prevalence of NASH is predicted to increase from 20.0% to 21.8%, proportion of NAFLD cases developing cirrhosis is expected to increase from 1.9% to 3.1%, and liver-related mortality is estimated to rise from 0.4% to 1% of all deaths.
The model also predicted that the burden of HCC will increase from 10,400 to 19,300 new cases per year, while liver transplant burden will more than double, from 1,700 to 4,200 transplants per year.
“Our model forecasts substantial clinical burden of NAFLD over the next three decades,” Dr. Le said in a virtual press conference. “And in the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant.”
During the press conference, Norah Terrault, MD, president of the AASLD from the University of Southern California, Los Angeles, noted that all of the reported outcomes, including increasing rates of liver cancer, cirrhosis, and transplants are “potentially preventable.”
Dr. Terrault went on to suggest ways of combating this increasing burden of NAFLD, which she referred to as metabolic dysfunction–associated steatotic liver disease (MASLD), the name now recommended by the AASLD.
“There’s no way we’re going to be able to transplant our way out of this,” Dr. Terrault said. “We need to be bringing greater awareness both to patients, as well as to providers about how we seek out the diagnosis. And we need to bring greater awareness to the population around the things that contribute to MASLD.”
Rates of obesity and diabetes continue to rise, Dr. Terrault said, explaining why MASLD is more common than ever. To counteract these trends, she called for greater awareness of driving factors, such as dietary choices and sedentary lifestyle.
“These are all really important messages that we want to get out to the population, and are really the cornerstones for how we approach the management of patients who have MASLD,” Dr. Terrault said.
In discussion with Dr. Terrault, Dr. Le agreed that increased education may help stem the rising tide of disease, while treatment advances could also increase the odds of a brighter future.
“If we improve our management of NAFLD, or NAFLD-related comorbidities, and if we can develop an effective treatment for NAFLD, then obviously the future would not be so dark,” Dr. Le said, noting promising phase 3 data that would be presented at the meeting. “We are hopeful that the future of disease burden will not be as bad as our model predicts.”
The study was funded by the Agency for Healthcare Research and Quality. The investigators disclosed no conflicts of interest.
, according to investigators.
These findings suggest that health care systems should prepare for “large increases” in cases of hepatocellular carcinoma (HCC) and need for liver transplants, reported lead author Phuc Le, PhD, MPH, of the Cleveland Clinic, and colleagues.
“Following the alarming rise in prevalence of obesity and diabetes, NAFLD is projected to become the leading indication for liver transplant in the United States in the next decade,” Dr. Le and colleagues wrote in their abstract for the annual meeting of the American Association for the Study of Liver Diseases. “A better understanding of the clinical burden associated with NAFLD will enable health systems to prepare to meet this imminent demand from patients.”
To this end, Dr. Le and colleagues developed an agent-based state transition model to predict future prevalence of NAFLD and associated outcomes.
In the first part of the model, the investigators simulated population growth in the United States using Census Bureau data, including new births and immigration, from the year 2000 onward. The second part of the model simulated natural progression of NAFLD in adults via 14 associated conditions and events, including steatosis, nonalcoholic steatohepatitis (NASH), HCC, liver transplants, liver-related mortality, and others.
By first comparing simulated findings with actual findings between 2000 and 2018, the investigators confirmed that their model could reliably predict the intended epidemiological parameters.
Next, they turned their model toward the future.
It predicted that the prevalence of NAFLD among US adults will rise from 27.8% in 2020 to 34.3% in 2050. Over the same timeframe, prevalence of NASH is predicted to increase from 20.0% to 21.8%, proportion of NAFLD cases developing cirrhosis is expected to increase from 1.9% to 3.1%, and liver-related mortality is estimated to rise from 0.4% to 1% of all deaths.
The model also predicted that the burden of HCC will increase from 10,400 to 19,300 new cases per year, while liver transplant burden will more than double, from 1,700 to 4,200 transplants per year.
“Our model forecasts substantial clinical burden of NAFLD over the next three decades,” Dr. Le said in a virtual press conference. “And in the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant.”
During the press conference, Norah Terrault, MD, president of the AASLD from the University of Southern California, Los Angeles, noted that all of the reported outcomes, including increasing rates of liver cancer, cirrhosis, and transplants are “potentially preventable.”
Dr. Terrault went on to suggest ways of combating this increasing burden of NAFLD, which she referred to as metabolic dysfunction–associated steatotic liver disease (MASLD), the name now recommended by the AASLD.
“There’s no way we’re going to be able to transplant our way out of this,” Dr. Terrault said. “We need to be bringing greater awareness both to patients, as well as to providers about how we seek out the diagnosis. And we need to bring greater awareness to the population around the things that contribute to MASLD.”
Rates of obesity and diabetes continue to rise, Dr. Terrault said, explaining why MASLD is more common than ever. To counteract these trends, she called for greater awareness of driving factors, such as dietary choices and sedentary lifestyle.
“These are all really important messages that we want to get out to the population, and are really the cornerstones for how we approach the management of patients who have MASLD,” Dr. Terrault said.
In discussion with Dr. Terrault, Dr. Le agreed that increased education may help stem the rising tide of disease, while treatment advances could also increase the odds of a brighter future.
“If we improve our management of NAFLD, or NAFLD-related comorbidities, and if we can develop an effective treatment for NAFLD, then obviously the future would not be so dark,” Dr. Le said, noting promising phase 3 data that would be presented at the meeting. “We are hopeful that the future of disease burden will not be as bad as our model predicts.”
The study was funded by the Agency for Healthcare Research and Quality. The investigators disclosed no conflicts of interest.
AT THE LIVER MEETING
Food insecurity increases risk of adolescent MASLD
, according to a recent study.
These findings suggest that more work is needed to ensure that eligible adolescents can access Supplemental Nutrition Assistance Program (SNAP) benefits and have opportunities to engage in physical activities through school-associated programs, reported principal investigator Zobair M. Younossi, MD, MPH, professor and chairman of the Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, and colleagues.
Dr. Younossi presented the findings in November during a press conference at the annual meeting of the American Association for the Study of Liver Diseases.
“Food insecurity among children is about 10.2% in the United States,” Dr. Younossi said. “[Food insecurity has] been shown to be a risk factor for MASLD among adults, but the data and children and adolescents are really lacking at the moment.”
To address this knowledge gap, Dr. Younossi and colleagues analyzed data from 771 adolescents aged 12-18 years in the National Health and Nutrition Examination Survey (2017-2018). Among these participants, 9.8% reported food insecurity and 10.8% had MASLD. Rates of obesity and central obesity were 22.5% and 45.4%, respectively, while 1.0% had diabetes and 20.9% had prediabetes.
Among adolescents facing food insecurity, more than half (51.5%) did not eat enough food, a vast majority (93.2%) could not access a balanced meal, and almost all (98.9%) relied upon low-cost food for daily sustenance.
The prevalence of MASLD in the food insecure group was almost twice as high as in the food secure group (18.7% vs 9.9%), and advanced fibrosis was about 9 times more common (2.8% vs. 0.3%). Food insecure participants were also more likely to come from a low-income household (70.4% vs. 25.7%) and participate in SNAP (62.4% vs. 25.1%).
Adjusting for SNAP participation, demographic factors, and metabolic disease showed that food insecurity independently increased risk of MASLD by more than twofold (odds ratio [OR], 2.62; 95% CI, 1.07–6.41). The negative effect of food insecurity was almost twice as strong in participants living in a low-income household (OR, 4.79; 95% CI, 1.44–15.86).
“The association between food insecurity and MASLD/NAFLD is most likely the result of not being able to eat a balanced meal and more likely having to purchase low-cost food,” Dr. Younossi said. “Together, these factors may lead to a cycle of overeating along with the overconsumption of ultra-processed foods and sugar-sweetened food and beverages.”
He went on to suggest that more work is needed to remove “systemic and structural barriers” that prevent eligible adolescents from participating in SNAP, while offering support so they can participate in “more physical activity in school and in after-school programs.”
Elliot Benjamin Tapper, MD, associate professor of medicine at the University of Michigan, Ann Arbor, recently published a similar study in the Journal of Clinical Gastroenterology linking food scarcity and MASLD in adults.
In an interview, Dr. Tapper praised this new study by Dr. Younossi and colleagues because it “identifies a serious unmet need” among younger individuals, who may stand to benefit most from early intervention.
“The goal [of screening] is to prevent the development of progressive disease,” Dr. Tapper said. “Our current guidelines for screening for advanced liver disease and people with risk factors focus exclusively on adults. If you waited longer, then there’s a risk that these [younger] people [in the study] would have progressed to a later stage of disease.”
Dr. Tapper predicted increased enthusiasm for MAFLD screening among adolescents in response to these findings, but he cautioned that conventional educational intervention is unlikely to yield significant benefit.
“If you’re food insecure, you can’t go out and buy salmon and olive oil to follow the Mediterranean diet,” Dr. Tapper said. In this era, where the people who are at risk tomorrow are young and food insecure, we have to come up with a way of tailoring our interventions to the means that are available to these patients.”
To this end, health care providers need to collaborate with individuals who have personally dealt with food scarcity to implement practicable interventions.
“Referral to social work has to be paired with some kind of standard teaching,” Dr. Tapper said. “How would I use social and nutritional assistance programs to eat in a liver-healthy way? What can I avoid? [Educational materials] should be written by and edited by people with lived experience; i.e., people who have food insecurity or have walked a mile in those shoes.”
Dr. Younossi disclosed relationships with Merck, Abbott, AstraZeneca, and others. Dr. Tapper disclosed relationships with Takeda, Novo Nordisk, Madrigal, and others.
, according to a recent study.
These findings suggest that more work is needed to ensure that eligible adolescents can access Supplemental Nutrition Assistance Program (SNAP) benefits and have opportunities to engage in physical activities through school-associated programs, reported principal investigator Zobair M. Younossi, MD, MPH, professor and chairman of the Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, and colleagues.
Dr. Younossi presented the findings in November during a press conference at the annual meeting of the American Association for the Study of Liver Diseases.
“Food insecurity among children is about 10.2% in the United States,” Dr. Younossi said. “[Food insecurity has] been shown to be a risk factor for MASLD among adults, but the data and children and adolescents are really lacking at the moment.”
To address this knowledge gap, Dr. Younossi and colleagues analyzed data from 771 adolescents aged 12-18 years in the National Health and Nutrition Examination Survey (2017-2018). Among these participants, 9.8% reported food insecurity and 10.8% had MASLD. Rates of obesity and central obesity were 22.5% and 45.4%, respectively, while 1.0% had diabetes and 20.9% had prediabetes.
Among adolescents facing food insecurity, more than half (51.5%) did not eat enough food, a vast majority (93.2%) could not access a balanced meal, and almost all (98.9%) relied upon low-cost food for daily sustenance.
The prevalence of MASLD in the food insecure group was almost twice as high as in the food secure group (18.7% vs 9.9%), and advanced fibrosis was about 9 times more common (2.8% vs. 0.3%). Food insecure participants were also more likely to come from a low-income household (70.4% vs. 25.7%) and participate in SNAP (62.4% vs. 25.1%).
Adjusting for SNAP participation, demographic factors, and metabolic disease showed that food insecurity independently increased risk of MASLD by more than twofold (odds ratio [OR], 2.62; 95% CI, 1.07–6.41). The negative effect of food insecurity was almost twice as strong in participants living in a low-income household (OR, 4.79; 95% CI, 1.44–15.86).
“The association between food insecurity and MASLD/NAFLD is most likely the result of not being able to eat a balanced meal and more likely having to purchase low-cost food,” Dr. Younossi said. “Together, these factors may lead to a cycle of overeating along with the overconsumption of ultra-processed foods and sugar-sweetened food and beverages.”
He went on to suggest that more work is needed to remove “systemic and structural barriers” that prevent eligible adolescents from participating in SNAP, while offering support so they can participate in “more physical activity in school and in after-school programs.”
Elliot Benjamin Tapper, MD, associate professor of medicine at the University of Michigan, Ann Arbor, recently published a similar study in the Journal of Clinical Gastroenterology linking food scarcity and MASLD in adults.
In an interview, Dr. Tapper praised this new study by Dr. Younossi and colleagues because it “identifies a serious unmet need” among younger individuals, who may stand to benefit most from early intervention.
“The goal [of screening] is to prevent the development of progressive disease,” Dr. Tapper said. “Our current guidelines for screening for advanced liver disease and people with risk factors focus exclusively on adults. If you waited longer, then there’s a risk that these [younger] people [in the study] would have progressed to a later stage of disease.”
Dr. Tapper predicted increased enthusiasm for MAFLD screening among adolescents in response to these findings, but he cautioned that conventional educational intervention is unlikely to yield significant benefit.
“If you’re food insecure, you can’t go out and buy salmon and olive oil to follow the Mediterranean diet,” Dr. Tapper said. In this era, where the people who are at risk tomorrow are young and food insecure, we have to come up with a way of tailoring our interventions to the means that are available to these patients.”
To this end, health care providers need to collaborate with individuals who have personally dealt with food scarcity to implement practicable interventions.
“Referral to social work has to be paired with some kind of standard teaching,” Dr. Tapper said. “How would I use social and nutritional assistance programs to eat in a liver-healthy way? What can I avoid? [Educational materials] should be written by and edited by people with lived experience; i.e., people who have food insecurity or have walked a mile in those shoes.”
Dr. Younossi disclosed relationships with Merck, Abbott, AstraZeneca, and others. Dr. Tapper disclosed relationships with Takeda, Novo Nordisk, Madrigal, and others.
, according to a recent study.
These findings suggest that more work is needed to ensure that eligible adolescents can access Supplemental Nutrition Assistance Program (SNAP) benefits and have opportunities to engage in physical activities through school-associated programs, reported principal investigator Zobair M. Younossi, MD, MPH, professor and chairman of the Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, and colleagues.
Dr. Younossi presented the findings in November during a press conference at the annual meeting of the American Association for the Study of Liver Diseases.
“Food insecurity among children is about 10.2% in the United States,” Dr. Younossi said. “[Food insecurity has] been shown to be a risk factor for MASLD among adults, but the data and children and adolescents are really lacking at the moment.”
To address this knowledge gap, Dr. Younossi and colleagues analyzed data from 771 adolescents aged 12-18 years in the National Health and Nutrition Examination Survey (2017-2018). Among these participants, 9.8% reported food insecurity and 10.8% had MASLD. Rates of obesity and central obesity were 22.5% and 45.4%, respectively, while 1.0% had diabetes and 20.9% had prediabetes.
Among adolescents facing food insecurity, more than half (51.5%) did not eat enough food, a vast majority (93.2%) could not access a balanced meal, and almost all (98.9%) relied upon low-cost food for daily sustenance.
The prevalence of MASLD in the food insecure group was almost twice as high as in the food secure group (18.7% vs 9.9%), and advanced fibrosis was about 9 times more common (2.8% vs. 0.3%). Food insecure participants were also more likely to come from a low-income household (70.4% vs. 25.7%) and participate in SNAP (62.4% vs. 25.1%).
Adjusting for SNAP participation, demographic factors, and metabolic disease showed that food insecurity independently increased risk of MASLD by more than twofold (odds ratio [OR], 2.62; 95% CI, 1.07–6.41). The negative effect of food insecurity was almost twice as strong in participants living in a low-income household (OR, 4.79; 95% CI, 1.44–15.86).
“The association between food insecurity and MASLD/NAFLD is most likely the result of not being able to eat a balanced meal and more likely having to purchase low-cost food,” Dr. Younossi said. “Together, these factors may lead to a cycle of overeating along with the overconsumption of ultra-processed foods and sugar-sweetened food and beverages.”
He went on to suggest that more work is needed to remove “systemic and structural barriers” that prevent eligible adolescents from participating in SNAP, while offering support so they can participate in “more physical activity in school and in after-school programs.”
Elliot Benjamin Tapper, MD, associate professor of medicine at the University of Michigan, Ann Arbor, recently published a similar study in the Journal of Clinical Gastroenterology linking food scarcity and MASLD in adults.
In an interview, Dr. Tapper praised this new study by Dr. Younossi and colleagues because it “identifies a serious unmet need” among younger individuals, who may stand to benefit most from early intervention.
“The goal [of screening] is to prevent the development of progressive disease,” Dr. Tapper said. “Our current guidelines for screening for advanced liver disease and people with risk factors focus exclusively on adults. If you waited longer, then there’s a risk that these [younger] people [in the study] would have progressed to a later stage of disease.”
Dr. Tapper predicted increased enthusiasm for MAFLD screening among adolescents in response to these findings, but he cautioned that conventional educational intervention is unlikely to yield significant benefit.
“If you’re food insecure, you can’t go out and buy salmon and olive oil to follow the Mediterranean diet,” Dr. Tapper said. In this era, where the people who are at risk tomorrow are young and food insecure, we have to come up with a way of tailoring our interventions to the means that are available to these patients.”
To this end, health care providers need to collaborate with individuals who have personally dealt with food scarcity to implement practicable interventions.
“Referral to social work has to be paired with some kind of standard teaching,” Dr. Tapper said. “How would I use social and nutritional assistance programs to eat in a liver-healthy way? What can I avoid? [Educational materials] should be written by and edited by people with lived experience; i.e., people who have food insecurity or have walked a mile in those shoes.”
Dr. Younossi disclosed relationships with Merck, Abbott, AstraZeneca, and others. Dr. Tapper disclosed relationships with Takeda, Novo Nordisk, Madrigal, and others.
AT THE LIVER MEETING
Pedunculated Verrucous Tumor on the Buttock
The Diagnosis: Giant Acrochordon
Based on the clinical and histologic findings, our patient was diagnosed with a giant acrochordon. Acrochordons (also known as fibroepithelial polyps or skin tags) are among the most commonly identified skin lesions and are believed to affect up to 46% of the general population.1,2 These benign growths typically appear after middle age in men and women alike and are believed to be of ectodermal and mesenchymal origin.3 The most common locations include the axillae, neck, and inguinal folds. They generally are small, measuring only a few millimeters, and frequently present as multiple lesions that are called giant acrochordons when their size exceeds 5 cm in length.2 Acrochordons are benign lesions with only rare reports of the presence of basal or squamous cell carcinoma within the lesion on pathology.4 In addition to being cosmetically unsightly, patients with acrochordons often report pruritus. These lesions are easily removed in an outpatient setting via snip excision, cryosurgery, or electrodesiccation. Once removed, recurrence is unlikely. Despite the prevalence of fibroepithelial polyps worldwide, reports of giant acrochordons are limited. The histopathology of giant acrochordons is similar to smaller acrochordons, with features including epidermal acanthosis and a central core of fibrovascular tissue without adnexal structures (Figure).4
The differential diagnosis of giant acrochordon includes neurofibroma, nodular melanoma, squamous cell carcinoma, and giant condylomata acuminata (Buschke-Löwenstein tumor).1 It is important to consider the clinical presentation and histopathologic findings to differentiate giant acrochordons from these other entities.
Neurofibromas typically present as multiple flesh-colored to brown nodules that invaginate into the skin when minimal external pressure is applied.5 Histopathology demonstrates a discrete, nonencapsulated, dermal collection of small nerve fibers and loosely arranged spindle cells. In contrast, giant acrochordons typically present as large, fleshcolored, pedunculated, verrucous tumors with a central stalk. Histopathology reveals epidermal acanthosis and a central core of fibrovascular tissue without adnexal structures.
Nodular melanomas usually are blue to black and grow rapidly over the course of several months.6 They have signs of hemorrhagic crust, and histopathology reveals atypical melanocytes, frequent mitoses, pleomorphic tumor cells, and irregular clumping of chromatin within the nuclei. Giant acrochordons are flesh colored, benign, and do not have these malignant features.
Squamous cell carcinoma often presents as an erythematous scaly patch or red plaque on sun-exposed areas of the skin.1 Histopathology of squamous cell carcinoma shows atypical keratinocytes with an invasive growth pattern; giant acrochordon does not show keratinocytic atypia or invasive epidermal growth.
Giant condylomata acuminata (Buschke-Löwenstein tumor) is a locally destructive verrucous plaque that typically appears on the penis but can occur elsewhere in the anogenital region.7 Histopathologic features include epidermal hyperplasia, papillomatosis, and koilocytes. In contrast, giant acrochordons typically are located on the buttocks and do not present with these epidermal changes.
Based on the clinical and histologic findings, our patient was diagnosed with a giant acrochordon, a rare variant of the common skin lesion. Excisional removal was critical for both diagnostic and treatment purposes. By considering the clinical presentation and histopathologic features of other conditions in the differential, giant acrochordons can be distinguished from other similar entities. Diagnosis and prompt surgical removal are important for management of these neoplasms and prevention of misdiagnosis.
- Alkhalili E, Prapasiri S, Russell J. Giant acrochordon of the axilla. BMJ Case Rep. 2015:bcr2015210623. doi:10.1136/bcr-2015-210623
- Banik R, Lubach D. Skin tags: localization and frequencies according to sex and age. Dermatologica. 1987;174:180-183. doi:10.1159/000249169
- Can B, Yildrim Ozluk A. Giant fibroepithelial polyps: why do they grow excessively? Med Bull Sisli Etfal Hastan Tip Bul. 2020;54:257-260. doi:10.14744/SEMB.2018.33603
- Ghosh SK, Bandyopadhyay D, Chatterjee G, et al. Giant skin tags on unusual locations. J Eur Acad Dermatol Venereol. 2009;23:233. doi:10.1111/j.1468-3083.2008.02816.x
- Messersmith L, Krauland K. Neurofibroma. StatPearls [Internet]. StatPearls Publishing; 2023.
- Saaiq M, Ashraf B, Siddiqui S. Nodular melanoma. Iran J Med Sci. 2016;41:164-165.
- Spinu D, Ra˘dulescu A, Bratu O, et al. Giant condyloma acuminatum. Buschke-Lowenstein disease: a literature review. Chirurgia (Bucur). 2014;109:445-450.
The Diagnosis: Giant Acrochordon
Based on the clinical and histologic findings, our patient was diagnosed with a giant acrochordon. Acrochordons (also known as fibroepithelial polyps or skin tags) are among the most commonly identified skin lesions and are believed to affect up to 46% of the general population.1,2 These benign growths typically appear after middle age in men and women alike and are believed to be of ectodermal and mesenchymal origin.3 The most common locations include the axillae, neck, and inguinal folds. They generally are small, measuring only a few millimeters, and frequently present as multiple lesions that are called giant acrochordons when their size exceeds 5 cm in length.2 Acrochordons are benign lesions with only rare reports of the presence of basal or squamous cell carcinoma within the lesion on pathology.4 In addition to being cosmetically unsightly, patients with acrochordons often report pruritus. These lesions are easily removed in an outpatient setting via snip excision, cryosurgery, or electrodesiccation. Once removed, recurrence is unlikely. Despite the prevalence of fibroepithelial polyps worldwide, reports of giant acrochordons are limited. The histopathology of giant acrochordons is similar to smaller acrochordons, with features including epidermal acanthosis and a central core of fibrovascular tissue without adnexal structures (Figure).4
The differential diagnosis of giant acrochordon includes neurofibroma, nodular melanoma, squamous cell carcinoma, and giant condylomata acuminata (Buschke-Löwenstein tumor).1 It is important to consider the clinical presentation and histopathologic findings to differentiate giant acrochordons from these other entities.
Neurofibromas typically present as multiple flesh-colored to brown nodules that invaginate into the skin when minimal external pressure is applied.5 Histopathology demonstrates a discrete, nonencapsulated, dermal collection of small nerve fibers and loosely arranged spindle cells. In contrast, giant acrochordons typically present as large, fleshcolored, pedunculated, verrucous tumors with a central stalk. Histopathology reveals epidermal acanthosis and a central core of fibrovascular tissue without adnexal structures.
Nodular melanomas usually are blue to black and grow rapidly over the course of several months.6 They have signs of hemorrhagic crust, and histopathology reveals atypical melanocytes, frequent mitoses, pleomorphic tumor cells, and irregular clumping of chromatin within the nuclei. Giant acrochordons are flesh colored, benign, and do not have these malignant features.
Squamous cell carcinoma often presents as an erythematous scaly patch or red plaque on sun-exposed areas of the skin.1 Histopathology of squamous cell carcinoma shows atypical keratinocytes with an invasive growth pattern; giant acrochordon does not show keratinocytic atypia or invasive epidermal growth.
Giant condylomata acuminata (Buschke-Löwenstein tumor) is a locally destructive verrucous plaque that typically appears on the penis but can occur elsewhere in the anogenital region.7 Histopathologic features include epidermal hyperplasia, papillomatosis, and koilocytes. In contrast, giant acrochordons typically are located on the buttocks and do not present with these epidermal changes.
Based on the clinical and histologic findings, our patient was diagnosed with a giant acrochordon, a rare variant of the common skin lesion. Excisional removal was critical for both diagnostic and treatment purposes. By considering the clinical presentation and histopathologic features of other conditions in the differential, giant acrochordons can be distinguished from other similar entities. Diagnosis and prompt surgical removal are important for management of these neoplasms and prevention of misdiagnosis.
The Diagnosis: Giant Acrochordon
Based on the clinical and histologic findings, our patient was diagnosed with a giant acrochordon. Acrochordons (also known as fibroepithelial polyps or skin tags) are among the most commonly identified skin lesions and are believed to affect up to 46% of the general population.1,2 These benign growths typically appear after middle age in men and women alike and are believed to be of ectodermal and mesenchymal origin.3 The most common locations include the axillae, neck, and inguinal folds. They generally are small, measuring only a few millimeters, and frequently present as multiple lesions that are called giant acrochordons when their size exceeds 5 cm in length.2 Acrochordons are benign lesions with only rare reports of the presence of basal or squamous cell carcinoma within the lesion on pathology.4 In addition to being cosmetically unsightly, patients with acrochordons often report pruritus. These lesions are easily removed in an outpatient setting via snip excision, cryosurgery, or electrodesiccation. Once removed, recurrence is unlikely. Despite the prevalence of fibroepithelial polyps worldwide, reports of giant acrochordons are limited. The histopathology of giant acrochordons is similar to smaller acrochordons, with features including epidermal acanthosis and a central core of fibrovascular tissue without adnexal structures (Figure).4
The differential diagnosis of giant acrochordon includes neurofibroma, nodular melanoma, squamous cell carcinoma, and giant condylomata acuminata (Buschke-Löwenstein tumor).1 It is important to consider the clinical presentation and histopathologic findings to differentiate giant acrochordons from these other entities.
Neurofibromas typically present as multiple flesh-colored to brown nodules that invaginate into the skin when minimal external pressure is applied.5 Histopathology demonstrates a discrete, nonencapsulated, dermal collection of small nerve fibers and loosely arranged spindle cells. In contrast, giant acrochordons typically present as large, fleshcolored, pedunculated, verrucous tumors with a central stalk. Histopathology reveals epidermal acanthosis and a central core of fibrovascular tissue without adnexal structures.
Nodular melanomas usually are blue to black and grow rapidly over the course of several months.6 They have signs of hemorrhagic crust, and histopathology reveals atypical melanocytes, frequent mitoses, pleomorphic tumor cells, and irregular clumping of chromatin within the nuclei. Giant acrochordons are flesh colored, benign, and do not have these malignant features.
Squamous cell carcinoma often presents as an erythematous scaly patch or red plaque on sun-exposed areas of the skin.1 Histopathology of squamous cell carcinoma shows atypical keratinocytes with an invasive growth pattern; giant acrochordon does not show keratinocytic atypia or invasive epidermal growth.
Giant condylomata acuminata (Buschke-Löwenstein tumor) is a locally destructive verrucous plaque that typically appears on the penis but can occur elsewhere in the anogenital region.7 Histopathologic features include epidermal hyperplasia, papillomatosis, and koilocytes. In contrast, giant acrochordons typically are located on the buttocks and do not present with these epidermal changes.
Based on the clinical and histologic findings, our patient was diagnosed with a giant acrochordon, a rare variant of the common skin lesion. Excisional removal was critical for both diagnostic and treatment purposes. By considering the clinical presentation and histopathologic features of other conditions in the differential, giant acrochordons can be distinguished from other similar entities. Diagnosis and prompt surgical removal are important for management of these neoplasms and prevention of misdiagnosis.
- Alkhalili E, Prapasiri S, Russell J. Giant acrochordon of the axilla. BMJ Case Rep. 2015:bcr2015210623. doi:10.1136/bcr-2015-210623
- Banik R, Lubach D. Skin tags: localization and frequencies according to sex and age. Dermatologica. 1987;174:180-183. doi:10.1159/000249169
- Can B, Yildrim Ozluk A. Giant fibroepithelial polyps: why do they grow excessively? Med Bull Sisli Etfal Hastan Tip Bul. 2020;54:257-260. doi:10.14744/SEMB.2018.33603
- Ghosh SK, Bandyopadhyay D, Chatterjee G, et al. Giant skin tags on unusual locations. J Eur Acad Dermatol Venereol. 2009;23:233. doi:10.1111/j.1468-3083.2008.02816.x
- Messersmith L, Krauland K. Neurofibroma. StatPearls [Internet]. StatPearls Publishing; 2023.
- Saaiq M, Ashraf B, Siddiqui S. Nodular melanoma. Iran J Med Sci. 2016;41:164-165.
- Spinu D, Ra˘dulescu A, Bratu O, et al. Giant condyloma acuminatum. Buschke-Lowenstein disease: a literature review. Chirurgia (Bucur). 2014;109:445-450.
- Alkhalili E, Prapasiri S, Russell J. Giant acrochordon of the axilla. BMJ Case Rep. 2015:bcr2015210623. doi:10.1136/bcr-2015-210623
- Banik R, Lubach D. Skin tags: localization and frequencies according to sex and age. Dermatologica. 1987;174:180-183. doi:10.1159/000249169
- Can B, Yildrim Ozluk A. Giant fibroepithelial polyps: why do they grow excessively? Med Bull Sisli Etfal Hastan Tip Bul. 2020;54:257-260. doi:10.14744/SEMB.2018.33603
- Ghosh SK, Bandyopadhyay D, Chatterjee G, et al. Giant skin tags on unusual locations. J Eur Acad Dermatol Venereol. 2009;23:233. doi:10.1111/j.1468-3083.2008.02816.x
- Messersmith L, Krauland K. Neurofibroma. StatPearls [Internet]. StatPearls Publishing; 2023.
- Saaiq M, Ashraf B, Siddiqui S. Nodular melanoma. Iran J Med Sci. 2016;41:164-165.
- Spinu D, Ra˘dulescu A, Bratu O, et al. Giant condyloma acuminatum. Buschke-Lowenstein disease: a literature review. Chirurgia (Bucur). 2014;109:445-450.
A 40-year-old man presented to our dermatology clinic with a growth on the left buttock of more than 22 years’ duration that progressively increased in size. He was otherwise in good health and reported no ongoing medical problems. Physical examination revealed a 19×12-cm, flesh-colored, pedunculated, verrucous tumor with a central stalk. The patient underwent an excisional removal, and the specimen was sent for histopathologic evaluation.
FDA approves pirtobrutinib for previously treated CLL/SLL
The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.
Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.
Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.
“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release.
Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.
Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.
A version of this article first appeared on Medscape.com.
The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.
Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.
Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.
“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release.
Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.
Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.
A version of this article first appeared on Medscape.com.
The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.
Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.
Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.
“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release.
Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.
Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.
A version of this article first appeared on Medscape.com.
Eight wealth tips just for doctors
The average physician makes $352,000, and some earn well into the $500,000s. So, doctors don’t have to worry about money, right?
You know the answer to that.
One thing all physicians have in common about money, says James M. Dahle, MD, FACEP, founder of The White Coat Investor, is that they don’t receive any training in business, personal finance, or investing throughout their schooling or careers unless they seek it out. This leaves many unprepared to make the best investing and money-saving decisions, while others get too frustrated about their lack of knowledge to even dip their toe into the investing pool.
Exhibit A: Four out of 10 physicians have a net worth below $1 million, according to the Medscape Physician Wealth & Debt Report 2023. Elizabeth Chiang, MD, PhD, an oculoplastic surgeon and a physician money coach at Grow Your Wealthy Mindset, notes that many of those doctors are over age 65, “which means they essentially can’t retire.”
And that’s just one pain point.
Physicians have money concerns specific to their profession and background. Luckily, some fellow doctors also serve as financial and wealth advisors just for other doctors.
Blind Spot #1
The early lean years skew doctors’ money outlook. “We have an extended training period, which commonly consists of taking on a large amount of debt, followed by 3 to 8 years of being paid a modest salary, and then finally a large boost in income,” explains Dr. Chiang. This can lay a shaky foundation for the earning years to come, and as a result, a lot of doctors just don’t think about money in healthy ways. Once their incomes increase, physicians may be surprised, for example, that making a multiple six-figure salary means paying six figures in taxes.
The Fix
Treat financial health like physical health. That means money cannot be a taboo subject. “The misguided mindset is that we didn’t become physicians to make money, we did it to help people,” explains Jordan Frey, MD, creator of the blog, The Prudent Plastic Surgeon.
Dr. Frey acknowledges that the desire to help is certainly true. But the result is a false idea that “to think about our personal finances makes us a worse doctor.”
Blind Spot #2
Because doctors know a lot about one thing (medicine), they might assume they know a lot about everything (such as investing). “Totally different fields with a different language and different way to think about it,” Dahle explains. This overconfidence could lead to some negligent or risky financial decisions.
The Fix
Educate yourself. There are several books on personal finance and investing written by physicians for physicians. Dr. Chiang recommends The Physician Philosopher’s Guide to Personal Finance, by James Turner, MD; Financial Freedom Rx, by Chirag Shah, MD, and Jayanth Sridhar, MD; and The Physician’s Guide to Finance, by Nicholas Christian and Amanda Christian, MD. There are also podcasts, blogs, and courses to help educate doctors on finance, such as the Fire Your Financial Advisor course by The White Coat Investor.
Blind Spot #3
Undersaving. Retirement saving is one thing, but 24% of doctors say they don’t even put money away in a taxable savings account, according to the Wealth & Debt Report.
Cobin Soelberg, MD, JD, a board-certified anesthesiologist and founder and principal advisor with Greeley Wealth Management, is the treasurer of his anesthesiology group. “I get to see every month how much people are saving, and even on an anesthesiologist salary, where everyone’s making about $400,000 a year, a lot of people are not saving anything, which is crazy.”
Undersaving can be both a time issue and a mindset one.
Time: Doctors often start investing in their retirement accounts later than the average professional, says Dr. Chiang. “A lot of physicians will max out their 401k or 403b,” she explains. “But if you’re putting in $20,000 a year and only starting when you’re in your early 30s, that’s not enough to get you to retirement.”
Mindset: Doctors also see people of all ages who are sick, dying, and injured. “They all know someone who worked hard and saved and then dropped dead at 55,” explains Dr. Dahle. This, he says, can lead to a bit of a “you only live once” attitude that prioritizes spending over saving.
The Fix
Shoot for 20%. If you can’t save 20% of your gross now, strive to get to that point. Think of it as telling a patient they have to change their behavior or trouble will come - not if, but when. “Develop a written investing plan and then stick with it through thick and thin,” says Dr. Dahle. “Once you have a reasonable plan, all you have to do is fund it adequately by saving 20% of your gross income, and a doctor will easily retire as a multimillionaire.”
Blind Spot #4
Bad investment strategies. Thirty-six percent of doctors experience their largest financial losses from lousy investments, according to the Wealth & Debt Report. Meanwhile, 17% of PCPs and 12% of specialists say they haven’t made any investments at all. That’s a terrible mix of doing the wrong thing and doing a worse thing.
The Fix
Don’t overthink investing, but don’t underthink it either. “As high-income earners, doctors just don’t need to take this high level of risk to reach their financial goals,” Dr. Frey says. A good investment plan doesn’t require you to time the stock market or predict individual stock winners. Consider what Vanguard founder Jack Bogle once said about investing: “Be bored by the process but elated by the outcome.”
Dr. Frey suggests going super-simple: index funds. Ignore investing strategies with actively managed mutual funds or individual stocks, as well as risky alternative investments such as cryptocurrency and angel investments. Everyone assumes doctors have money to burn, and they will push sketchy investment ideas at them. Avoid.
Blind Spot #5
Not taking debt seriously enough. The average medical student debt is $250,000 and can exceed $500,000, says Dr. Soelberg. Many doctors spend the first 10 to 20 years of their careers paying this off. Today’s graduates are paying more than 7% on their loans.
And it’s not just student debt: 39% of physicians carry five or more credit cards, and 34% have mortgages larger than $300,000 (with half of those are more than than $500K), per the Wealth & Debt Report.
The Fix
Treat debt like cancer. It’s a lethal enemy you can’t get rid of right away, but a steady, aggressive, long-term attack will have the best results. Dr. Soelberg suggests allocating the most you can afford per month, whether that’s $1000 or $5000, toward debt. Raise the amount as your income grows. Do the same with your 401k or retirement plan. Whatever is left, you can spend. Five to 10 years later, you will realize, “Wow. I’m debt free.”
Blind Spot #6
Not putting in the work to improve your situation. Seventy-one percent of doctors admit they haven’t done anything to reduce major expenses, according to the Wealth & Debt Report. Are you leaving major money on the table?
The Fix
Audit yourself in major areas like housing and taxes. While the average professional may need to put 10% to 20% down on a home, physicians can qualify for physician mortgage loans and can often put down 3% or less, says Dr. Chiang. If you can afford the higher mortgage payment, excess savings earmarked for a larger down payment can be put toward debt or invested.
Another trick, if you’re able, is to seek an area that is less in demand at a higher salary. “Physicians in places like New York City or San Francisco tend to make less than physicians in the Midwest or the South,” Dr. Chiang explains. A colleague of hers moved to rural Pennsylvania, where he made a high salary and had a low cost of living for 3½ years, paid off his student debt, and then relocated to an area where he wanted to live long term.
As for taxes, become familiar with tax law. Research things like, “What is considered a business expense for doctors?” says Brett Mollard, MD, a diagnostic radiologist who provides financial advice to younger physicians. “What will your estimated total tax burden be at the end of the year? Will you need to make extra payments to prevent owing a large sum of money from underpaying or to avoid tax penalties?”
Blind Spot #7
Living like a rock star on a doctor’s income. Getting caught up in trying to live the same lifestyle as your colleagues is a classic bear trap. “Sitting in the doctor’s lounge, it’s so crazy,” Dr. Soelberg says. He describes conversations like, “‘Where did you go on your trip?’ ‘What new toys are you buying?’” There’s pressure to live up to an image of what a doctor’s life is supposed to look like before you’ve sorted the basic things like paying off debt.
The Fix
Live like a resident even if you haven’t been one for years, at least until you’re in a better financial position. “You’re already used to living a life of lower means, and you’re an expert when it comes to delaying gratification,” says Dr. Mollard. “Do it a little longer.” Live frugally and spend only on things that bring you joy. “A lot of physicians are trying to be really rich in all areas of their life instead of the ones that actually matter to them,” Dr. Soelberg says. Identify what’s important to you and only splurge on that.
Blind Spot #8
Never asking for help. The right financial planner can provide expert help. Emphasis on right. “Doctors can be very trusting of other professionals, even when they should not be,” says Dr. Dahle. He notes that in financial services, many people masquerade as knowledgeable advisors who are really just salespeople. While legitimate financial advisors strive to make their clients money, they are also ultimately out to line their pockets and love to work with physician salaries. Thus, doctors can end up working with financial planners that don’t specifically understand their situations or end up taking too much from their clients.
The Fix
Find a planner who specializes in, or at least understands, physicians. Ask them how they make money, says Dr. Chiang. If someone hesitates to tell you about their fee structure or if it sounds like a lot, shop around and ask colleagues for recommendations.
“Ultimately, the path to wealth is to create and grow the margin between what you make and what you spend,” says Dr. Frey. Throw some investing into the mix and physicians can set themselves up on a path for a stress-free financial life.
A version of this article appeared on Medscape.com.
The average physician makes $352,000, and some earn well into the $500,000s. So, doctors don’t have to worry about money, right?
You know the answer to that.
One thing all physicians have in common about money, says James M. Dahle, MD, FACEP, founder of The White Coat Investor, is that they don’t receive any training in business, personal finance, or investing throughout their schooling or careers unless they seek it out. This leaves many unprepared to make the best investing and money-saving decisions, while others get too frustrated about their lack of knowledge to even dip their toe into the investing pool.
Exhibit A: Four out of 10 physicians have a net worth below $1 million, according to the Medscape Physician Wealth & Debt Report 2023. Elizabeth Chiang, MD, PhD, an oculoplastic surgeon and a physician money coach at Grow Your Wealthy Mindset, notes that many of those doctors are over age 65, “which means they essentially can’t retire.”
And that’s just one pain point.
Physicians have money concerns specific to their profession and background. Luckily, some fellow doctors also serve as financial and wealth advisors just for other doctors.
Blind Spot #1
The early lean years skew doctors’ money outlook. “We have an extended training period, which commonly consists of taking on a large amount of debt, followed by 3 to 8 years of being paid a modest salary, and then finally a large boost in income,” explains Dr. Chiang. This can lay a shaky foundation for the earning years to come, and as a result, a lot of doctors just don’t think about money in healthy ways. Once their incomes increase, physicians may be surprised, for example, that making a multiple six-figure salary means paying six figures in taxes.
The Fix
Treat financial health like physical health. That means money cannot be a taboo subject. “The misguided mindset is that we didn’t become physicians to make money, we did it to help people,” explains Jordan Frey, MD, creator of the blog, The Prudent Plastic Surgeon.
Dr. Frey acknowledges that the desire to help is certainly true. But the result is a false idea that “to think about our personal finances makes us a worse doctor.”
Blind Spot #2
Because doctors know a lot about one thing (medicine), they might assume they know a lot about everything (such as investing). “Totally different fields with a different language and different way to think about it,” Dahle explains. This overconfidence could lead to some negligent or risky financial decisions.
The Fix
Educate yourself. There are several books on personal finance and investing written by physicians for physicians. Dr. Chiang recommends The Physician Philosopher’s Guide to Personal Finance, by James Turner, MD; Financial Freedom Rx, by Chirag Shah, MD, and Jayanth Sridhar, MD; and The Physician’s Guide to Finance, by Nicholas Christian and Amanda Christian, MD. There are also podcasts, blogs, and courses to help educate doctors on finance, such as the Fire Your Financial Advisor course by The White Coat Investor.
Blind Spot #3
Undersaving. Retirement saving is one thing, but 24% of doctors say they don’t even put money away in a taxable savings account, according to the Wealth & Debt Report.
Cobin Soelberg, MD, JD, a board-certified anesthesiologist and founder and principal advisor with Greeley Wealth Management, is the treasurer of his anesthesiology group. “I get to see every month how much people are saving, and even on an anesthesiologist salary, where everyone’s making about $400,000 a year, a lot of people are not saving anything, which is crazy.”
Undersaving can be both a time issue and a mindset one.
Time: Doctors often start investing in their retirement accounts later than the average professional, says Dr. Chiang. “A lot of physicians will max out their 401k or 403b,” she explains. “But if you’re putting in $20,000 a year and only starting when you’re in your early 30s, that’s not enough to get you to retirement.”
Mindset: Doctors also see people of all ages who are sick, dying, and injured. “They all know someone who worked hard and saved and then dropped dead at 55,” explains Dr. Dahle. This, he says, can lead to a bit of a “you only live once” attitude that prioritizes spending over saving.
The Fix
Shoot for 20%. If you can’t save 20% of your gross now, strive to get to that point. Think of it as telling a patient they have to change their behavior or trouble will come - not if, but when. “Develop a written investing plan and then stick with it through thick and thin,” says Dr. Dahle. “Once you have a reasonable plan, all you have to do is fund it adequately by saving 20% of your gross income, and a doctor will easily retire as a multimillionaire.”
Blind Spot #4
Bad investment strategies. Thirty-six percent of doctors experience their largest financial losses from lousy investments, according to the Wealth & Debt Report. Meanwhile, 17% of PCPs and 12% of specialists say they haven’t made any investments at all. That’s a terrible mix of doing the wrong thing and doing a worse thing.
The Fix
Don’t overthink investing, but don’t underthink it either. “As high-income earners, doctors just don’t need to take this high level of risk to reach their financial goals,” Dr. Frey says. A good investment plan doesn’t require you to time the stock market or predict individual stock winners. Consider what Vanguard founder Jack Bogle once said about investing: “Be bored by the process but elated by the outcome.”
Dr. Frey suggests going super-simple: index funds. Ignore investing strategies with actively managed mutual funds or individual stocks, as well as risky alternative investments such as cryptocurrency and angel investments. Everyone assumes doctors have money to burn, and they will push sketchy investment ideas at them. Avoid.
Blind Spot #5
Not taking debt seriously enough. The average medical student debt is $250,000 and can exceed $500,000, says Dr. Soelberg. Many doctors spend the first 10 to 20 years of their careers paying this off. Today’s graduates are paying more than 7% on their loans.
And it’s not just student debt: 39% of physicians carry five or more credit cards, and 34% have mortgages larger than $300,000 (with half of those are more than than $500K), per the Wealth & Debt Report.
The Fix
Treat debt like cancer. It’s a lethal enemy you can’t get rid of right away, but a steady, aggressive, long-term attack will have the best results. Dr. Soelberg suggests allocating the most you can afford per month, whether that’s $1000 or $5000, toward debt. Raise the amount as your income grows. Do the same with your 401k or retirement plan. Whatever is left, you can spend. Five to 10 years later, you will realize, “Wow. I’m debt free.”
Blind Spot #6
Not putting in the work to improve your situation. Seventy-one percent of doctors admit they haven’t done anything to reduce major expenses, according to the Wealth & Debt Report. Are you leaving major money on the table?
The Fix
Audit yourself in major areas like housing and taxes. While the average professional may need to put 10% to 20% down on a home, physicians can qualify for physician mortgage loans and can often put down 3% or less, says Dr. Chiang. If you can afford the higher mortgage payment, excess savings earmarked for a larger down payment can be put toward debt or invested.
Another trick, if you’re able, is to seek an area that is less in demand at a higher salary. “Physicians in places like New York City or San Francisco tend to make less than physicians in the Midwest or the South,” Dr. Chiang explains. A colleague of hers moved to rural Pennsylvania, where he made a high salary and had a low cost of living for 3½ years, paid off his student debt, and then relocated to an area where he wanted to live long term.
As for taxes, become familiar with tax law. Research things like, “What is considered a business expense for doctors?” says Brett Mollard, MD, a diagnostic radiologist who provides financial advice to younger physicians. “What will your estimated total tax burden be at the end of the year? Will you need to make extra payments to prevent owing a large sum of money from underpaying or to avoid tax penalties?”
Blind Spot #7
Living like a rock star on a doctor’s income. Getting caught up in trying to live the same lifestyle as your colleagues is a classic bear trap. “Sitting in the doctor’s lounge, it’s so crazy,” Dr. Soelberg says. He describes conversations like, “‘Where did you go on your trip?’ ‘What new toys are you buying?’” There’s pressure to live up to an image of what a doctor’s life is supposed to look like before you’ve sorted the basic things like paying off debt.
The Fix
Live like a resident even if you haven’t been one for years, at least until you’re in a better financial position. “You’re already used to living a life of lower means, and you’re an expert when it comes to delaying gratification,” says Dr. Mollard. “Do it a little longer.” Live frugally and spend only on things that bring you joy. “A lot of physicians are trying to be really rich in all areas of their life instead of the ones that actually matter to them,” Dr. Soelberg says. Identify what’s important to you and only splurge on that.
Blind Spot #8
Never asking for help. The right financial planner can provide expert help. Emphasis on right. “Doctors can be very trusting of other professionals, even when they should not be,” says Dr. Dahle. He notes that in financial services, many people masquerade as knowledgeable advisors who are really just salespeople. While legitimate financial advisors strive to make their clients money, they are also ultimately out to line their pockets and love to work with physician salaries. Thus, doctors can end up working with financial planners that don’t specifically understand their situations or end up taking too much from their clients.
The Fix
Find a planner who specializes in, or at least understands, physicians. Ask them how they make money, says Dr. Chiang. If someone hesitates to tell you about their fee structure or if it sounds like a lot, shop around and ask colleagues for recommendations.
“Ultimately, the path to wealth is to create and grow the margin between what you make and what you spend,” says Dr. Frey. Throw some investing into the mix and physicians can set themselves up on a path for a stress-free financial life.
A version of this article appeared on Medscape.com.
The average physician makes $352,000, and some earn well into the $500,000s. So, doctors don’t have to worry about money, right?
You know the answer to that.
One thing all physicians have in common about money, says James M. Dahle, MD, FACEP, founder of The White Coat Investor, is that they don’t receive any training in business, personal finance, or investing throughout their schooling or careers unless they seek it out. This leaves many unprepared to make the best investing and money-saving decisions, while others get too frustrated about their lack of knowledge to even dip their toe into the investing pool.
Exhibit A: Four out of 10 physicians have a net worth below $1 million, according to the Medscape Physician Wealth & Debt Report 2023. Elizabeth Chiang, MD, PhD, an oculoplastic surgeon and a physician money coach at Grow Your Wealthy Mindset, notes that many of those doctors are over age 65, “which means they essentially can’t retire.”
And that’s just one pain point.
Physicians have money concerns specific to their profession and background. Luckily, some fellow doctors also serve as financial and wealth advisors just for other doctors.
Blind Spot #1
The early lean years skew doctors’ money outlook. “We have an extended training period, which commonly consists of taking on a large amount of debt, followed by 3 to 8 years of being paid a modest salary, and then finally a large boost in income,” explains Dr. Chiang. This can lay a shaky foundation for the earning years to come, and as a result, a lot of doctors just don’t think about money in healthy ways. Once their incomes increase, physicians may be surprised, for example, that making a multiple six-figure salary means paying six figures in taxes.
The Fix
Treat financial health like physical health. That means money cannot be a taboo subject. “The misguided mindset is that we didn’t become physicians to make money, we did it to help people,” explains Jordan Frey, MD, creator of the blog, The Prudent Plastic Surgeon.
Dr. Frey acknowledges that the desire to help is certainly true. But the result is a false idea that “to think about our personal finances makes us a worse doctor.”
Blind Spot #2
Because doctors know a lot about one thing (medicine), they might assume they know a lot about everything (such as investing). “Totally different fields with a different language and different way to think about it,” Dahle explains. This overconfidence could lead to some negligent or risky financial decisions.
The Fix
Educate yourself. There are several books on personal finance and investing written by physicians for physicians. Dr. Chiang recommends The Physician Philosopher’s Guide to Personal Finance, by James Turner, MD; Financial Freedom Rx, by Chirag Shah, MD, and Jayanth Sridhar, MD; and The Physician’s Guide to Finance, by Nicholas Christian and Amanda Christian, MD. There are also podcasts, blogs, and courses to help educate doctors on finance, such as the Fire Your Financial Advisor course by The White Coat Investor.
Blind Spot #3
Undersaving. Retirement saving is one thing, but 24% of doctors say they don’t even put money away in a taxable savings account, according to the Wealth & Debt Report.
Cobin Soelberg, MD, JD, a board-certified anesthesiologist and founder and principal advisor with Greeley Wealth Management, is the treasurer of his anesthesiology group. “I get to see every month how much people are saving, and even on an anesthesiologist salary, where everyone’s making about $400,000 a year, a lot of people are not saving anything, which is crazy.”
Undersaving can be both a time issue and a mindset one.
Time: Doctors often start investing in their retirement accounts later than the average professional, says Dr. Chiang. “A lot of physicians will max out their 401k or 403b,” she explains. “But if you’re putting in $20,000 a year and only starting when you’re in your early 30s, that’s not enough to get you to retirement.”
Mindset: Doctors also see people of all ages who are sick, dying, and injured. “They all know someone who worked hard and saved and then dropped dead at 55,” explains Dr. Dahle. This, he says, can lead to a bit of a “you only live once” attitude that prioritizes spending over saving.
The Fix
Shoot for 20%. If you can’t save 20% of your gross now, strive to get to that point. Think of it as telling a patient they have to change their behavior or trouble will come - not if, but when. “Develop a written investing plan and then stick with it through thick and thin,” says Dr. Dahle. “Once you have a reasonable plan, all you have to do is fund it adequately by saving 20% of your gross income, and a doctor will easily retire as a multimillionaire.”
Blind Spot #4
Bad investment strategies. Thirty-six percent of doctors experience their largest financial losses from lousy investments, according to the Wealth & Debt Report. Meanwhile, 17% of PCPs and 12% of specialists say they haven’t made any investments at all. That’s a terrible mix of doing the wrong thing and doing a worse thing.
The Fix
Don’t overthink investing, but don’t underthink it either. “As high-income earners, doctors just don’t need to take this high level of risk to reach their financial goals,” Dr. Frey says. A good investment plan doesn’t require you to time the stock market or predict individual stock winners. Consider what Vanguard founder Jack Bogle once said about investing: “Be bored by the process but elated by the outcome.”
Dr. Frey suggests going super-simple: index funds. Ignore investing strategies with actively managed mutual funds or individual stocks, as well as risky alternative investments such as cryptocurrency and angel investments. Everyone assumes doctors have money to burn, and they will push sketchy investment ideas at them. Avoid.
Blind Spot #5
Not taking debt seriously enough. The average medical student debt is $250,000 and can exceed $500,000, says Dr. Soelberg. Many doctors spend the first 10 to 20 years of their careers paying this off. Today’s graduates are paying more than 7% on their loans.
And it’s not just student debt: 39% of physicians carry five or more credit cards, and 34% have mortgages larger than $300,000 (with half of those are more than than $500K), per the Wealth & Debt Report.
The Fix
Treat debt like cancer. It’s a lethal enemy you can’t get rid of right away, but a steady, aggressive, long-term attack will have the best results. Dr. Soelberg suggests allocating the most you can afford per month, whether that’s $1000 or $5000, toward debt. Raise the amount as your income grows. Do the same with your 401k or retirement plan. Whatever is left, you can spend. Five to 10 years later, you will realize, “Wow. I’m debt free.”
Blind Spot #6
Not putting in the work to improve your situation. Seventy-one percent of doctors admit they haven’t done anything to reduce major expenses, according to the Wealth & Debt Report. Are you leaving major money on the table?
The Fix
Audit yourself in major areas like housing and taxes. While the average professional may need to put 10% to 20% down on a home, physicians can qualify for physician mortgage loans and can often put down 3% or less, says Dr. Chiang. If you can afford the higher mortgage payment, excess savings earmarked for a larger down payment can be put toward debt or invested.
Another trick, if you’re able, is to seek an area that is less in demand at a higher salary. “Physicians in places like New York City or San Francisco tend to make less than physicians in the Midwest or the South,” Dr. Chiang explains. A colleague of hers moved to rural Pennsylvania, where he made a high salary and had a low cost of living for 3½ years, paid off his student debt, and then relocated to an area where he wanted to live long term.
As for taxes, become familiar with tax law. Research things like, “What is considered a business expense for doctors?” says Brett Mollard, MD, a diagnostic radiologist who provides financial advice to younger physicians. “What will your estimated total tax burden be at the end of the year? Will you need to make extra payments to prevent owing a large sum of money from underpaying or to avoid tax penalties?”
Blind Spot #7
Living like a rock star on a doctor’s income. Getting caught up in trying to live the same lifestyle as your colleagues is a classic bear trap. “Sitting in the doctor’s lounge, it’s so crazy,” Dr. Soelberg says. He describes conversations like, “‘Where did you go on your trip?’ ‘What new toys are you buying?’” There’s pressure to live up to an image of what a doctor’s life is supposed to look like before you’ve sorted the basic things like paying off debt.
The Fix
Live like a resident even if you haven’t been one for years, at least until you’re in a better financial position. “You’re already used to living a life of lower means, and you’re an expert when it comes to delaying gratification,” says Dr. Mollard. “Do it a little longer.” Live frugally and spend only on things that bring you joy. “A lot of physicians are trying to be really rich in all areas of their life instead of the ones that actually matter to them,” Dr. Soelberg says. Identify what’s important to you and only splurge on that.
Blind Spot #8
Never asking for help. The right financial planner can provide expert help. Emphasis on right. “Doctors can be very trusting of other professionals, even when they should not be,” says Dr. Dahle. He notes that in financial services, many people masquerade as knowledgeable advisors who are really just salespeople. While legitimate financial advisors strive to make their clients money, they are also ultimately out to line their pockets and love to work with physician salaries. Thus, doctors can end up working with financial planners that don’t specifically understand their situations or end up taking too much from their clients.
The Fix
Find a planner who specializes in, or at least understands, physicians. Ask them how they make money, says Dr. Chiang. If someone hesitates to tell you about their fee structure or if it sounds like a lot, shop around and ask colleagues for recommendations.
“Ultimately, the path to wealth is to create and grow the margin between what you make and what you spend,” says Dr. Frey. Throw some investing into the mix and physicians can set themselves up on a path for a stress-free financial life.
A version of this article appeared on Medscape.com.
PFO closure may reduce migraine days and prevent stroke
, according to a discussion at the 2023 Scottsdale Headache Symposium.
In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.
Other right-to-left shunt defects have also been associated with both migraine and stroke, leading Dr. Charles to suggest these defects are more a common denominator.
“Stroke during a migraine is, in fact, very uncommon,” Dr. Charles said. “This raises the possibility that it is not the migraine causing the stroke but rather there is a shared risk factor for stroke and migraine,” said Dr. Charles, referring to PFO as well as other right-to-left shunt defects, such as hereditary hemorrhaging telangiectasia in the lungs.
One Intervention, Two Potential Benefits
Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.
Use of oral contraceptives, which produce a hypercoagulable state, is an example.
“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.
The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
Primary Endpoint Missed in Clinical Trials
The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.
In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).
A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.
There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.
Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.
“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
Migraine Days Might Be a Better Endpoint
For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.
“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.
He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.
One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.
Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.
Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.
“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.
Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”
In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).
The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”
As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.
“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.
Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.
, according to a discussion at the 2023 Scottsdale Headache Symposium.
In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.
Other right-to-left shunt defects have also been associated with both migraine and stroke, leading Dr. Charles to suggest these defects are more a common denominator.
“Stroke during a migraine is, in fact, very uncommon,” Dr. Charles said. “This raises the possibility that it is not the migraine causing the stroke but rather there is a shared risk factor for stroke and migraine,” said Dr. Charles, referring to PFO as well as other right-to-left shunt defects, such as hereditary hemorrhaging telangiectasia in the lungs.
One Intervention, Two Potential Benefits
Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.
Use of oral contraceptives, which produce a hypercoagulable state, is an example.
“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.
The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
Primary Endpoint Missed in Clinical Trials
The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.
In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).
A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.
There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.
Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.
“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
Migraine Days Might Be a Better Endpoint
For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.
“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.
He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.
One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.
Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.
Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.
“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.
Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”
In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).
The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”
As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.
“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.
Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.
, according to a discussion at the 2023 Scottsdale Headache Symposium.
In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.
Other right-to-left shunt defects have also been associated with both migraine and stroke, leading Dr. Charles to suggest these defects are more a common denominator.
“Stroke during a migraine is, in fact, very uncommon,” Dr. Charles said. “This raises the possibility that it is not the migraine causing the stroke but rather there is a shared risk factor for stroke and migraine,” said Dr. Charles, referring to PFO as well as other right-to-left shunt defects, such as hereditary hemorrhaging telangiectasia in the lungs.
One Intervention, Two Potential Benefits
Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.
Use of oral contraceptives, which produce a hypercoagulable state, is an example.
“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.
The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
Primary Endpoint Missed in Clinical Trials
The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.
In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).
A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.
There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.
Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.
“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
Migraine Days Might Be a Better Endpoint
For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.
“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.
He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.
One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.
Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.
Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.
“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.
Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”
In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).
The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”
As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.
“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.
Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.
FROM THE 2023 SCOTTSDALE HEADACHE SYMPOSIUM