User login
MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Tenapanor Shows Response in IBS-C Within Weeks: Pooled Data Analysis
“Although onset of action occurs within the first week, continued therapy allows for a greater percentage of patients to achieve a meaningful response,” wrote Brian Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, and co-authors in an abstract.
Dr. Lacy presented the results of this work at the annual scientific meeting of the American College of Gastroenterology (ACG) in Vancouver, Canada.
Tenapanor acts as an inhibitor of the sodium-hydrogen exchanger 3 (NHE3) and works to reduce dietary sodium absorption, which, in turn, leads to retention of fluid in the intestinal lumen, resulting in softer stool and accelerated intestinal transit, he explained.
Tenapanor is approved by the US Food and Drug Administration for adults with IBS-C.
The major goal of the analysis presented at ACG was to identify times to responses for individual symptoms, said Dr. Lacy in an email exchange with GI & Hepatology News.
Prior studies focused on global improvement in IBS-C symptoms using the FDA-approved definition of a responder: A patient who experienced at least a 30% reduction in the weekly average abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least 6 of the first 12 treatment weeks.
“Thus, we thought it important to pool all of the data together for this post-hoc analysis, as clinicians and patients often wonder when an individual symptom will respond,” Dr. Lacy wrote in an email.
Dr. Lacy and colleagues conducted a post hoc analysis of pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies to evaluate time to onset of tenapanor effect on bowel function and on individual and global abdominal symptoms in patients with IBS-C.
This resulted in a pooled population of 1372 intent-to-treat patients (688 placebo, 684 on the study drug), with demographics generally similar across the studies, they said.
They found that the median time to CSBM was 2 weeks, with an estimated response probability of 52.3% by week 2, 72.5% by week 8, and 76.7% by week 12.
The median time to abdominal pain response was 4 weeks; the estimated response probability was 54.6% by week 4, 67.9% by week 8, and 72.3% by week 12.
The median time to abdominal bloating response was 5 weeks; the estimated response probability was 48.1% by week 4, 61.9% by week 8, and 67.7% by week 12.
“The teaching message to patients and providers is not to give up too early; staying on this medication allowed 25% more people to improve symptoms,” Dr. Lacy wrote.
In separate interviews, two other researchers Anthony Lembo, MD, AGAF, director of research for Cleveland Clinic’s Digestive Disease & Surgery Institute, and Brooks D. Cash, MD, AGAF, chief for gastroenterology, hepatology, and nutrition at the University of Texas Health Science Center at Houston, agreed with Dr. Lacy’s message.
The study will help in counseling patients who may need to wait a bit to see a response from tenapanor, Dr. Lembo said.
“You wish patients would get better right away of course,” he said, but there can be some delay, even in cases where a drug will ultimately work for a patient.
Patients want to know if they should continue and if it is worth getting another prescription for another month if they haven’t had a significant improvement response, Dr. Lembo said.
Both Dr. Lembo and Dr. Cash said that it takes time for many drugs, not just these medications, to produce a noticeable effect for patients.
Still, “disorders of the gut-brain interaction likely do require a longer runway time to really assess their effects on multiple symptoms,” Dr. Cash said.
The tenapanor research presented at ACG will help in conveying that message to patients, Dr. Cash said.
“It also reinforces for clinicians not to be impatient,” he said.
Dr. Lacy and co-authors directed the development of the poster, and medical writing support was provided by Ashfield MedComms, an Inizio company, and funded by Ardelyx. Dr. Lacy has financial and consulting relationships with AbbVie, Ardelyx, Gernelli, Ironwood Pharmaceuticals, Salix, and Sanofi, Co-authors are employees of Ardelyx. Dr. Lembo and Dr. Cash have financial relationships with Ardelyx and other makers of IBS drugs.
“Although onset of action occurs within the first week, continued therapy allows for a greater percentage of patients to achieve a meaningful response,” wrote Brian Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, and co-authors in an abstract.
Dr. Lacy presented the results of this work at the annual scientific meeting of the American College of Gastroenterology (ACG) in Vancouver, Canada.
Tenapanor acts as an inhibitor of the sodium-hydrogen exchanger 3 (NHE3) and works to reduce dietary sodium absorption, which, in turn, leads to retention of fluid in the intestinal lumen, resulting in softer stool and accelerated intestinal transit, he explained.
Tenapanor is approved by the US Food and Drug Administration for adults with IBS-C.
The major goal of the analysis presented at ACG was to identify times to responses for individual symptoms, said Dr. Lacy in an email exchange with GI & Hepatology News.
Prior studies focused on global improvement in IBS-C symptoms using the FDA-approved definition of a responder: A patient who experienced at least a 30% reduction in the weekly average abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least 6 of the first 12 treatment weeks.
“Thus, we thought it important to pool all of the data together for this post-hoc analysis, as clinicians and patients often wonder when an individual symptom will respond,” Dr. Lacy wrote in an email.
Dr. Lacy and colleagues conducted a post hoc analysis of pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies to evaluate time to onset of tenapanor effect on bowel function and on individual and global abdominal symptoms in patients with IBS-C.
This resulted in a pooled population of 1372 intent-to-treat patients (688 placebo, 684 on the study drug), with demographics generally similar across the studies, they said.
They found that the median time to CSBM was 2 weeks, with an estimated response probability of 52.3% by week 2, 72.5% by week 8, and 76.7% by week 12.
The median time to abdominal pain response was 4 weeks; the estimated response probability was 54.6% by week 4, 67.9% by week 8, and 72.3% by week 12.
The median time to abdominal bloating response was 5 weeks; the estimated response probability was 48.1% by week 4, 61.9% by week 8, and 67.7% by week 12.
“The teaching message to patients and providers is not to give up too early; staying on this medication allowed 25% more people to improve symptoms,” Dr. Lacy wrote.
In separate interviews, two other researchers Anthony Lembo, MD, AGAF, director of research for Cleveland Clinic’s Digestive Disease & Surgery Institute, and Brooks D. Cash, MD, AGAF, chief for gastroenterology, hepatology, and nutrition at the University of Texas Health Science Center at Houston, agreed with Dr. Lacy’s message.
The study will help in counseling patients who may need to wait a bit to see a response from tenapanor, Dr. Lembo said.
“You wish patients would get better right away of course,” he said, but there can be some delay, even in cases where a drug will ultimately work for a patient.
Patients want to know if they should continue and if it is worth getting another prescription for another month if they haven’t had a significant improvement response, Dr. Lembo said.
Both Dr. Lembo and Dr. Cash said that it takes time for many drugs, not just these medications, to produce a noticeable effect for patients.
Still, “disorders of the gut-brain interaction likely do require a longer runway time to really assess their effects on multiple symptoms,” Dr. Cash said.
The tenapanor research presented at ACG will help in conveying that message to patients, Dr. Cash said.
“It also reinforces for clinicians not to be impatient,” he said.
Dr. Lacy and co-authors directed the development of the poster, and medical writing support was provided by Ashfield MedComms, an Inizio company, and funded by Ardelyx. Dr. Lacy has financial and consulting relationships with AbbVie, Ardelyx, Gernelli, Ironwood Pharmaceuticals, Salix, and Sanofi, Co-authors are employees of Ardelyx. Dr. Lembo and Dr. Cash have financial relationships with Ardelyx and other makers of IBS drugs.
“Although onset of action occurs within the first week, continued therapy allows for a greater percentage of patients to achieve a meaningful response,” wrote Brian Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, and co-authors in an abstract.
Dr. Lacy presented the results of this work at the annual scientific meeting of the American College of Gastroenterology (ACG) in Vancouver, Canada.
Tenapanor acts as an inhibitor of the sodium-hydrogen exchanger 3 (NHE3) and works to reduce dietary sodium absorption, which, in turn, leads to retention of fluid in the intestinal lumen, resulting in softer stool and accelerated intestinal transit, he explained.
Tenapanor is approved by the US Food and Drug Administration for adults with IBS-C.
The major goal of the analysis presented at ACG was to identify times to responses for individual symptoms, said Dr. Lacy in an email exchange with GI & Hepatology News.
Prior studies focused on global improvement in IBS-C symptoms using the FDA-approved definition of a responder: A patient who experienced at least a 30% reduction in the weekly average abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least 6 of the first 12 treatment weeks.
“Thus, we thought it important to pool all of the data together for this post-hoc analysis, as clinicians and patients often wonder when an individual symptom will respond,” Dr. Lacy wrote in an email.
Dr. Lacy and colleagues conducted a post hoc analysis of pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies to evaluate time to onset of tenapanor effect on bowel function and on individual and global abdominal symptoms in patients with IBS-C.
This resulted in a pooled population of 1372 intent-to-treat patients (688 placebo, 684 on the study drug), with demographics generally similar across the studies, they said.
They found that the median time to CSBM was 2 weeks, with an estimated response probability of 52.3% by week 2, 72.5% by week 8, and 76.7% by week 12.
The median time to abdominal pain response was 4 weeks; the estimated response probability was 54.6% by week 4, 67.9% by week 8, and 72.3% by week 12.
The median time to abdominal bloating response was 5 weeks; the estimated response probability was 48.1% by week 4, 61.9% by week 8, and 67.7% by week 12.
“The teaching message to patients and providers is not to give up too early; staying on this medication allowed 25% more people to improve symptoms,” Dr. Lacy wrote.
In separate interviews, two other researchers Anthony Lembo, MD, AGAF, director of research for Cleveland Clinic’s Digestive Disease & Surgery Institute, and Brooks D. Cash, MD, AGAF, chief for gastroenterology, hepatology, and nutrition at the University of Texas Health Science Center at Houston, agreed with Dr. Lacy’s message.
The study will help in counseling patients who may need to wait a bit to see a response from tenapanor, Dr. Lembo said.
“You wish patients would get better right away of course,” he said, but there can be some delay, even in cases where a drug will ultimately work for a patient.
Patients want to know if they should continue and if it is worth getting another prescription for another month if they haven’t had a significant improvement response, Dr. Lembo said.
Both Dr. Lembo and Dr. Cash said that it takes time for many drugs, not just these medications, to produce a noticeable effect for patients.
Still, “disorders of the gut-brain interaction likely do require a longer runway time to really assess their effects on multiple symptoms,” Dr. Cash said.
The tenapanor research presented at ACG will help in conveying that message to patients, Dr. Cash said.
“It also reinforces for clinicians not to be impatient,” he said.
Dr. Lacy and co-authors directed the development of the poster, and medical writing support was provided by Ashfield MedComms, an Inizio company, and funded by Ardelyx. Dr. Lacy has financial and consulting relationships with AbbVie, Ardelyx, Gernelli, Ironwood Pharmaceuticals, Salix, and Sanofi, Co-authors are employees of Ardelyx. Dr. Lembo and Dr. Cash have financial relationships with Ardelyx and other makers of IBS drugs.
FROM ACG 2023
Hair Loss in Children: How to Spot and Treat Different Causes
ORLANDO, FLORIDA — There are subtleties and nuances to diagnosing, treating, and monitoring the progress of treatment of hair loss in children. Moreover, hair loss in children can be challenging because it can be caused by a range of conditions, some common and others relatively rare.
Michelle Oboite, MD, shared tips on how to distinguish types of hair loss, when to treat with medications such as topical corticosteroids or Janus kinase (JAK) inhibitors, and why shared decision-making is important, at the ODAC Dermatology, Aesthetic & Surgical Conference.
What these conditions share is that they can negatively affect the quality of life for a child or teenager when the condition leads to anxiety, teasing, or bullying. “It is very isolating to have this condition that everyone in the world can see that you have and judge you for it,” said Dr. Oboite, an attending physician in the dermatology section of Children’s Hospital of Philadelphia.
Others are lichen planopilaris and genetic conditions, including loose anagen syndrome, uncombable hair syndrome, and “something so rare” — it has no acronym — autosomal recessive hypotrichosis with recurrent skin vesicles, Dr. Oboite said.
Alopecia Areata
Alopecia areata can differ from child to child and can appear in different stages: A localized patch stage, a diffuse patchy stage, or alopecia universalis. In this last stage, the child has already lost most or all the hair on the scalp and eyebrows, as well as the eyelashes.
The decision to treat or not to treat, particularly in younger children, should be on the basis of shared decision-making between a healthcare provider and caregiver, said Dr. Oboite, who is also an assistant professor of clinical dermatology at the University of Pennsylvania, Philadelphia.
Some younger children may not experience any negative impact from the condition, so waiting until they are older is an option.
Also, consider the impact of treatment on a child. Some therapies require frequent blood draws for monitoring, and some topical therapies that are applied multiple times a day “can be very overwhelming” for young children, Dr. Oboite said.
Most children with alopecia areata are healthy and do not need extensive screening laboratory testing. However, one exception is if thyroid dysfunction, commonly associated with alopecia areata, is suspected.
For alopecia areata, Dr. Oboite recommends starting with topical therapies, either topical corticosteroids (as first line) or topical JAK inhibitors (either topical ruxolitinib or compounded topical tofacitinib, both off-label for this indication).
Topical corticosteroids can be effective, but “you want to be thoughtful of the strength you’re using, the application frequency, and then the total amount of surface area that you’re treating,” Dr. Oboite said. Too potent or too much of a topical corticosteroid increases the risk for atrophy and systemic absorption, respectively. To reduce the risk, she reserves the use of ultrahigh-potency topical corticosteroids, such as clobetasol, for children ages 10 years or older. For children younger than 10 years, she recommends using mid-high-potency topical corticosteroids instead.
She recommends once-a-day application around bedtime 5 days a week, generally Monday through Friday to make it easier to remember.
“For children who have over 50% of the scalp involved, I do consider systemic therapy,” Dr. Oboite said. This can include oral steroids such as dexamethasone, prednisone, or prednisolone. For children with recalcitrant disease, she is more likely to use the oral JAK inhibitor ritlecitinib because it was recently approved by the Food and Drug Administration for treating severe alopecia areata in children 12 years and older and in adults.
Another strategy Dr. Oboite uses is to add low-dose oral minoxidil as an adjuvant to other systemic therapy. “I find that it helps with faster hair regrowth,” she said.
Tinea Capitis
Oral treatment is indicated for tinea capitis. “Topicals just don’t really clear this,” Dr. Oboite said. Also, talk to patients and families about preventing reinfection with the dermatophyte that causes this condition. “Make sure we’re cleaning hats, combs, brushes, and pillowcases. That is really important.”
Some patients can develop a widespread rash while on treatment. But in most cases, it’s not an adverse reaction to the medication but rather an indication that the body’s response is revving up, she noted.
Griseofulvin 20 mg/kg/d is one treatment option. Another is terbinafine (using weight-based dosing). A tip with terbinafine is that because the tablet needs to be crushed for a young child, “you can put it in anything, besides applesauce or yogurt with fruit on the bottom, which can be acidic and reduce the effectiveness of the medication,” Dr. Oboite said.
For cases of severe, inflammatory tinea capitis such as a kerion, “I will say you have to hold the hands of these patients, the journey can be long,” she added.
Trichotillomania
Trichotillomania occurs when someone cannot stop pulling their own hair, and in the early phases, it can be confused with alopecia areata. A thorough history and examination of the patient can help distinguish the two conditions. Sometimes a child or teen has a history of anxiety-related behaviors like nail biting that points to trichotillomania. Another tip is to use a dermatoscope to help distinguish hair loss conditions because it avoids having to do as many biopsies in children.
Redirection therapy can work for younger children, and cognitive behavioral therapy (CBT) can help older children with trichotillomania. In response to a question during the Q&A period, Dr. Oboite said psychiatrists or psychologists can perform CBT. If it takes time to get an appointment, there are some CBT apps that can help in the meantime, she said.
“One thing really important is to not blame the child,” Dr. Oboite said. “Most children don’t even know that they’re doing this. This is often not a behavior that is being done on purpose.”
Androgenetic Alopecia
Rarely, children and teenagers can also present with androgenetic alopecia, which Dr. Oboite has successfully treated with topical minoxidil, applied once a day before increasing to twice a day if tolerated. “I will tell them that when they pick it up, it will say ‘you should not use in children.’ But it actually can be used in children safely.”
Low-dose oral minoxidil is another option. Both treatments require a commitment by patients and parents because they are “taking this for a long time.”
Loose Anagen and Uncombable Hair Syndromes
A rare genetic form of hair loss is called loose anagen syndrome. Children with this disorder will have thin hair that is easily pulled out without a lot of force. Their hair appears to typically only grow to a certain length (such as to the nape of the neck) and then stops.
Another genetic hair loss condition is uncombable hair syndrome. It can cause hair to grow out of the scalp in all directions, and as the name suggests, it is almost impossible to comb or brush down. Along with loose anagen syndrome, uncombable hair syndrome tends to improve as the child gets older. “The key point here is telling parents that it can get better with time,” Dr. Oboite said.
A Condition With No Well-Known Acronym
She described a child she treated who had hair that never grew and was easily broken. The patient’s skin was prone to bruising, and her fingernails would easily fall off after trauma; her dentist noted that she had no buds for adult teeth on x-rays. These different presentations are important because hair, teeth, and nails all come from the same ectoderm germ line in embryo development, Dr. Oboite said.
Exome sequencing revealed the girl had a very rare diagnosis called autosomal recessive hypotrichosis with recurrent skin vesicles. “So, it is really important to recognize that children who are presenting with hair issues can have a genetic, underlying condition,” she said. Examining the skin, nails, and teeth, in addition to the hair, can be clues to these very rare diagnoses.
Some of these hair loss conditions in children can be challenging to diagnose and manage, Dr. Oboite said. “So don’t be afraid to ask for help on complex or rare cases.” Pediatric dermatologists “are always happy to help you. Hair loss is daunting, and hair loss in children can be even more daunting,” but the rewards of accurate diagnosis and successful treatment can be great, she said.
Dr. Oboite reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
ORLANDO, FLORIDA — There are subtleties and nuances to diagnosing, treating, and monitoring the progress of treatment of hair loss in children. Moreover, hair loss in children can be challenging because it can be caused by a range of conditions, some common and others relatively rare.
Michelle Oboite, MD, shared tips on how to distinguish types of hair loss, when to treat with medications such as topical corticosteroids or Janus kinase (JAK) inhibitors, and why shared decision-making is important, at the ODAC Dermatology, Aesthetic & Surgical Conference.
What these conditions share is that they can negatively affect the quality of life for a child or teenager when the condition leads to anxiety, teasing, or bullying. “It is very isolating to have this condition that everyone in the world can see that you have and judge you for it,” said Dr. Oboite, an attending physician in the dermatology section of Children’s Hospital of Philadelphia.
Others are lichen planopilaris and genetic conditions, including loose anagen syndrome, uncombable hair syndrome, and “something so rare” — it has no acronym — autosomal recessive hypotrichosis with recurrent skin vesicles, Dr. Oboite said.
Alopecia Areata
Alopecia areata can differ from child to child and can appear in different stages: A localized patch stage, a diffuse patchy stage, or alopecia universalis. In this last stage, the child has already lost most or all the hair on the scalp and eyebrows, as well as the eyelashes.
The decision to treat or not to treat, particularly in younger children, should be on the basis of shared decision-making between a healthcare provider and caregiver, said Dr. Oboite, who is also an assistant professor of clinical dermatology at the University of Pennsylvania, Philadelphia.
Some younger children may not experience any negative impact from the condition, so waiting until they are older is an option.
Also, consider the impact of treatment on a child. Some therapies require frequent blood draws for monitoring, and some topical therapies that are applied multiple times a day “can be very overwhelming” for young children, Dr. Oboite said.
Most children with alopecia areata are healthy and do not need extensive screening laboratory testing. However, one exception is if thyroid dysfunction, commonly associated with alopecia areata, is suspected.
For alopecia areata, Dr. Oboite recommends starting with topical therapies, either topical corticosteroids (as first line) or topical JAK inhibitors (either topical ruxolitinib or compounded topical tofacitinib, both off-label for this indication).
Topical corticosteroids can be effective, but “you want to be thoughtful of the strength you’re using, the application frequency, and then the total amount of surface area that you’re treating,” Dr. Oboite said. Too potent or too much of a topical corticosteroid increases the risk for atrophy and systemic absorption, respectively. To reduce the risk, she reserves the use of ultrahigh-potency topical corticosteroids, such as clobetasol, for children ages 10 years or older. For children younger than 10 years, she recommends using mid-high-potency topical corticosteroids instead.
She recommends once-a-day application around bedtime 5 days a week, generally Monday through Friday to make it easier to remember.
“For children who have over 50% of the scalp involved, I do consider systemic therapy,” Dr. Oboite said. This can include oral steroids such as dexamethasone, prednisone, or prednisolone. For children with recalcitrant disease, she is more likely to use the oral JAK inhibitor ritlecitinib because it was recently approved by the Food and Drug Administration for treating severe alopecia areata in children 12 years and older and in adults.
Another strategy Dr. Oboite uses is to add low-dose oral minoxidil as an adjuvant to other systemic therapy. “I find that it helps with faster hair regrowth,” she said.
Tinea Capitis
Oral treatment is indicated for tinea capitis. “Topicals just don’t really clear this,” Dr. Oboite said. Also, talk to patients and families about preventing reinfection with the dermatophyte that causes this condition. “Make sure we’re cleaning hats, combs, brushes, and pillowcases. That is really important.”
Some patients can develop a widespread rash while on treatment. But in most cases, it’s not an adverse reaction to the medication but rather an indication that the body’s response is revving up, she noted.
Griseofulvin 20 mg/kg/d is one treatment option. Another is terbinafine (using weight-based dosing). A tip with terbinafine is that because the tablet needs to be crushed for a young child, “you can put it in anything, besides applesauce or yogurt with fruit on the bottom, which can be acidic and reduce the effectiveness of the medication,” Dr. Oboite said.
For cases of severe, inflammatory tinea capitis such as a kerion, “I will say you have to hold the hands of these patients, the journey can be long,” she added.
Trichotillomania
Trichotillomania occurs when someone cannot stop pulling their own hair, and in the early phases, it can be confused with alopecia areata. A thorough history and examination of the patient can help distinguish the two conditions. Sometimes a child or teen has a history of anxiety-related behaviors like nail biting that points to trichotillomania. Another tip is to use a dermatoscope to help distinguish hair loss conditions because it avoids having to do as many biopsies in children.
Redirection therapy can work for younger children, and cognitive behavioral therapy (CBT) can help older children with trichotillomania. In response to a question during the Q&A period, Dr. Oboite said psychiatrists or psychologists can perform CBT. If it takes time to get an appointment, there are some CBT apps that can help in the meantime, she said.
“One thing really important is to not blame the child,” Dr. Oboite said. “Most children don’t even know that they’re doing this. This is often not a behavior that is being done on purpose.”
Androgenetic Alopecia
Rarely, children and teenagers can also present with androgenetic alopecia, which Dr. Oboite has successfully treated with topical minoxidil, applied once a day before increasing to twice a day if tolerated. “I will tell them that when they pick it up, it will say ‘you should not use in children.’ But it actually can be used in children safely.”
Low-dose oral minoxidil is another option. Both treatments require a commitment by patients and parents because they are “taking this for a long time.”
Loose Anagen and Uncombable Hair Syndromes
A rare genetic form of hair loss is called loose anagen syndrome. Children with this disorder will have thin hair that is easily pulled out without a lot of force. Their hair appears to typically only grow to a certain length (such as to the nape of the neck) and then stops.
Another genetic hair loss condition is uncombable hair syndrome. It can cause hair to grow out of the scalp in all directions, and as the name suggests, it is almost impossible to comb or brush down. Along with loose anagen syndrome, uncombable hair syndrome tends to improve as the child gets older. “The key point here is telling parents that it can get better with time,” Dr. Oboite said.
A Condition With No Well-Known Acronym
She described a child she treated who had hair that never grew and was easily broken. The patient’s skin was prone to bruising, and her fingernails would easily fall off after trauma; her dentist noted that she had no buds for adult teeth on x-rays. These different presentations are important because hair, teeth, and nails all come from the same ectoderm germ line in embryo development, Dr. Oboite said.
Exome sequencing revealed the girl had a very rare diagnosis called autosomal recessive hypotrichosis with recurrent skin vesicles. “So, it is really important to recognize that children who are presenting with hair issues can have a genetic, underlying condition,” she said. Examining the skin, nails, and teeth, in addition to the hair, can be clues to these very rare diagnoses.
Some of these hair loss conditions in children can be challenging to diagnose and manage, Dr. Oboite said. “So don’t be afraid to ask for help on complex or rare cases.” Pediatric dermatologists “are always happy to help you. Hair loss is daunting, and hair loss in children can be even more daunting,” but the rewards of accurate diagnosis and successful treatment can be great, she said.
Dr. Oboite reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
ORLANDO, FLORIDA — There are subtleties and nuances to diagnosing, treating, and monitoring the progress of treatment of hair loss in children. Moreover, hair loss in children can be challenging because it can be caused by a range of conditions, some common and others relatively rare.
Michelle Oboite, MD, shared tips on how to distinguish types of hair loss, when to treat with medications such as topical corticosteroids or Janus kinase (JAK) inhibitors, and why shared decision-making is important, at the ODAC Dermatology, Aesthetic & Surgical Conference.
What these conditions share is that they can negatively affect the quality of life for a child or teenager when the condition leads to anxiety, teasing, or bullying. “It is very isolating to have this condition that everyone in the world can see that you have and judge you for it,” said Dr. Oboite, an attending physician in the dermatology section of Children’s Hospital of Philadelphia.
Others are lichen planopilaris and genetic conditions, including loose anagen syndrome, uncombable hair syndrome, and “something so rare” — it has no acronym — autosomal recessive hypotrichosis with recurrent skin vesicles, Dr. Oboite said.
Alopecia Areata
Alopecia areata can differ from child to child and can appear in different stages: A localized patch stage, a diffuse patchy stage, or alopecia universalis. In this last stage, the child has already lost most or all the hair on the scalp and eyebrows, as well as the eyelashes.
The decision to treat or not to treat, particularly in younger children, should be on the basis of shared decision-making between a healthcare provider and caregiver, said Dr. Oboite, who is also an assistant professor of clinical dermatology at the University of Pennsylvania, Philadelphia.
Some younger children may not experience any negative impact from the condition, so waiting until they are older is an option.
Also, consider the impact of treatment on a child. Some therapies require frequent blood draws for monitoring, and some topical therapies that are applied multiple times a day “can be very overwhelming” for young children, Dr. Oboite said.
Most children with alopecia areata are healthy and do not need extensive screening laboratory testing. However, one exception is if thyroid dysfunction, commonly associated with alopecia areata, is suspected.
For alopecia areata, Dr. Oboite recommends starting with topical therapies, either topical corticosteroids (as first line) or topical JAK inhibitors (either topical ruxolitinib or compounded topical tofacitinib, both off-label for this indication).
Topical corticosteroids can be effective, but “you want to be thoughtful of the strength you’re using, the application frequency, and then the total amount of surface area that you’re treating,” Dr. Oboite said. Too potent or too much of a topical corticosteroid increases the risk for atrophy and systemic absorption, respectively. To reduce the risk, she reserves the use of ultrahigh-potency topical corticosteroids, such as clobetasol, for children ages 10 years or older. For children younger than 10 years, she recommends using mid-high-potency topical corticosteroids instead.
She recommends once-a-day application around bedtime 5 days a week, generally Monday through Friday to make it easier to remember.
“For children who have over 50% of the scalp involved, I do consider systemic therapy,” Dr. Oboite said. This can include oral steroids such as dexamethasone, prednisone, or prednisolone. For children with recalcitrant disease, she is more likely to use the oral JAK inhibitor ritlecitinib because it was recently approved by the Food and Drug Administration for treating severe alopecia areata in children 12 years and older and in adults.
Another strategy Dr. Oboite uses is to add low-dose oral minoxidil as an adjuvant to other systemic therapy. “I find that it helps with faster hair regrowth,” she said.
Tinea Capitis
Oral treatment is indicated for tinea capitis. “Topicals just don’t really clear this,” Dr. Oboite said. Also, talk to patients and families about preventing reinfection with the dermatophyte that causes this condition. “Make sure we’re cleaning hats, combs, brushes, and pillowcases. That is really important.”
Some patients can develop a widespread rash while on treatment. But in most cases, it’s not an adverse reaction to the medication but rather an indication that the body’s response is revving up, she noted.
Griseofulvin 20 mg/kg/d is one treatment option. Another is terbinafine (using weight-based dosing). A tip with terbinafine is that because the tablet needs to be crushed for a young child, “you can put it in anything, besides applesauce or yogurt with fruit on the bottom, which can be acidic and reduce the effectiveness of the medication,” Dr. Oboite said.
For cases of severe, inflammatory tinea capitis such as a kerion, “I will say you have to hold the hands of these patients, the journey can be long,” she added.
Trichotillomania
Trichotillomania occurs when someone cannot stop pulling their own hair, and in the early phases, it can be confused with alopecia areata. A thorough history and examination of the patient can help distinguish the two conditions. Sometimes a child or teen has a history of anxiety-related behaviors like nail biting that points to trichotillomania. Another tip is to use a dermatoscope to help distinguish hair loss conditions because it avoids having to do as many biopsies in children.
Redirection therapy can work for younger children, and cognitive behavioral therapy (CBT) can help older children with trichotillomania. In response to a question during the Q&A period, Dr. Oboite said psychiatrists or psychologists can perform CBT. If it takes time to get an appointment, there are some CBT apps that can help in the meantime, she said.
“One thing really important is to not blame the child,” Dr. Oboite said. “Most children don’t even know that they’re doing this. This is often not a behavior that is being done on purpose.”
Androgenetic Alopecia
Rarely, children and teenagers can also present with androgenetic alopecia, which Dr. Oboite has successfully treated with topical minoxidil, applied once a day before increasing to twice a day if tolerated. “I will tell them that when they pick it up, it will say ‘you should not use in children.’ But it actually can be used in children safely.”
Low-dose oral minoxidil is another option. Both treatments require a commitment by patients and parents because they are “taking this for a long time.”
Loose Anagen and Uncombable Hair Syndromes
A rare genetic form of hair loss is called loose anagen syndrome. Children with this disorder will have thin hair that is easily pulled out without a lot of force. Their hair appears to typically only grow to a certain length (such as to the nape of the neck) and then stops.
Another genetic hair loss condition is uncombable hair syndrome. It can cause hair to grow out of the scalp in all directions, and as the name suggests, it is almost impossible to comb or brush down. Along with loose anagen syndrome, uncombable hair syndrome tends to improve as the child gets older. “The key point here is telling parents that it can get better with time,” Dr. Oboite said.
A Condition With No Well-Known Acronym
She described a child she treated who had hair that never grew and was easily broken. The patient’s skin was prone to bruising, and her fingernails would easily fall off after trauma; her dentist noted that she had no buds for adult teeth on x-rays. These different presentations are important because hair, teeth, and nails all come from the same ectoderm germ line in embryo development, Dr. Oboite said.
Exome sequencing revealed the girl had a very rare diagnosis called autosomal recessive hypotrichosis with recurrent skin vesicles. “So, it is really important to recognize that children who are presenting with hair issues can have a genetic, underlying condition,” she said. Examining the skin, nails, and teeth, in addition to the hair, can be clues to these very rare diagnoses.
Some of these hair loss conditions in children can be challenging to diagnose and manage, Dr. Oboite said. “So don’t be afraid to ask for help on complex or rare cases.” Pediatric dermatologists “are always happy to help you. Hair loss is daunting, and hair loss in children can be even more daunting,” but the rewards of accurate diagnosis and successful treatment can be great, she said.
Dr. Oboite reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
AT ODAC 2024
A Look at the Evidence Linking Diet to Skin Conditions
ORLANDO, FLORIDA — Amid all the hype, claims, and confusion, there is evidence linking some foods and drinks to an increased risk for acne, psoriasis, atopic dermatitis, rosacea, and other common skin conditions. So, what is the connection in each case? And how can people with any of these skin conditions potentially improve their health and quality of life with dietary changes?
What is clear is that there has been an explosion of interest in learning which foods can improve or worsen skin issues in recent years. It’s a good idea to familiarize yourself with the research and also to Google ‘diet’ and ‘skin’, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas for Medical Sciences, Little Rock. “As practitioners, we should be well prepared to talk about what patients want to talk about.”
Acne
One of the major areas of interest is diet and acne. “We’ve all heard sugar and dairy are bad, and the Western diet is high in sugar and dairy,” Dr. Shi said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dairy, red meat, and carbohydrates can break down into leucine, an essential amino acid found in protein. Leucine and sugar together, in turn, can produce insulin and insulin-like growth factor 1 (IGF-1), which, through different pathways, can reach the androgen receptors throughout the body, including the skin. This results in sebogenesis, lipogenesis, and keratinization, which triggers follicular inflammation and results in more of the acne-causing bacteria Cutibacterium acnes.
Milk and other dairy products also can increase IGF-1 levels, which can alter hormonal mediators and increase acne.
Not all types of dairy milk are created equal, however, when it comes to acne. Dr. Shi wondered why 2% milk has overall color and nutritional content very similar to that of whole milk. “I looked into this.” She discovered that when milk manufacturers remove the fat, they often add whey proteins to restore some nutrients. Whey protein can increase acne, Dr. Shi added.
“So, if you’re going to choose any milk to drink, I think from an acne perspective, it’s better to use whole milk. If you can get it organic, even better.” Skim milk is the most acnegenic, she said.
Psoriasis
A systematic review of 55 studies evaluating diet and psoriasis found obesity can be an exacerbating factor. The strongest evidence for dietary weight reduction points to a hypocaloric diet in people with overweight or obesity, according to the review. Other evidence suggests alcohol can lower response to treatment and is linked with more severe psoriasis. Furthermore, a gluten-free diet or vitamin D supplements can help some subpopulations of people with psoriasis.
“An overwhelming majority of our psoriasis patients are vitamin D deficient,” Dr. Shi said.
The National Psoriasis Foundation (NPF) publishes dietary modification guidelines, updated as recently as November 2023. The NPF states that “there is no diet that will cure psoriatic disease, but there are many ways in which eating healthful food may lessen the severity of symptoms and play a role in lowering the likelihood of developing comorbidities.”
Healthier choices include fruits, vegetables, whole grains, and fat-free or low-fat dairy products. Include lean meats, poultry, fish, beans, eggs, and nuts. Adherence to a Mediterranean diet has been linked to a lower severity of psoriasis.
Atopic Dermatitis
Atopic dermatitis (AD) is “one of the prototypical diseases related to diet,” Dr. Shi said. A different meta-analysis looked at randomized controlled trials of synbiotics (a combination of prebiotics and probiotics) for treatment of AD.
These researchers found that synbiotics do not prevent AD, but they can help treat it in adults and children older than 1 year. In addition, synbiotics are more beneficial than probiotics in treating the condition, although there are no head-to-head comparison studies. In addition, the meta-analysis found that prebiotics alone can lower AD severity.
However, Dr. Shi said, there are no recommendations from the American Academy of Dermatology (AAD) on prebiotics or probiotics for AD, and the AAD does not recommend any supplement or essential oil for AD.
In a 2022 review, investigators ranked the efficacy of different supplements for AD based on available evidence. They found the greatest benefit associated with vitamin D supplementation, followed by vitamin E, probiotics, hemp seed oil, histidine, and oolong tea. They also noted the ‘Six Food Elimination Diet and Autoimmune Protocol’ featured the least amount of evidence to back it up.
Rosacea
Rosacea appears to be caused by “all the fun things in life” like sunlight, alcohol, chocolate, spicy foods, and caffeine, Dr. Shi said. In people with rosacea, they can cause facial flushing, edema, burning, and an inflammatory response.
Certain foods can activate skin receptors and sensory neurons, which can release neuropeptides that act on mast cells in blood that lead to flushing. The skin-gut axis may also be involved, evidence suggests. “And that is why food has a pretty profound impact on rosacea,” Dr. Shi said.
Dr. Shi reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
ORLANDO, FLORIDA — Amid all the hype, claims, and confusion, there is evidence linking some foods and drinks to an increased risk for acne, psoriasis, atopic dermatitis, rosacea, and other common skin conditions. So, what is the connection in each case? And how can people with any of these skin conditions potentially improve their health and quality of life with dietary changes?
What is clear is that there has been an explosion of interest in learning which foods can improve or worsen skin issues in recent years. It’s a good idea to familiarize yourself with the research and also to Google ‘diet’ and ‘skin’, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas for Medical Sciences, Little Rock. “As practitioners, we should be well prepared to talk about what patients want to talk about.”
Acne
One of the major areas of interest is diet and acne. “We’ve all heard sugar and dairy are bad, and the Western diet is high in sugar and dairy,” Dr. Shi said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dairy, red meat, and carbohydrates can break down into leucine, an essential amino acid found in protein. Leucine and sugar together, in turn, can produce insulin and insulin-like growth factor 1 (IGF-1), which, through different pathways, can reach the androgen receptors throughout the body, including the skin. This results in sebogenesis, lipogenesis, and keratinization, which triggers follicular inflammation and results in more of the acne-causing bacteria Cutibacterium acnes.
Milk and other dairy products also can increase IGF-1 levels, which can alter hormonal mediators and increase acne.
Not all types of dairy milk are created equal, however, when it comes to acne. Dr. Shi wondered why 2% milk has overall color and nutritional content very similar to that of whole milk. “I looked into this.” She discovered that when milk manufacturers remove the fat, they often add whey proteins to restore some nutrients. Whey protein can increase acne, Dr. Shi added.
“So, if you’re going to choose any milk to drink, I think from an acne perspective, it’s better to use whole milk. If you can get it organic, even better.” Skim milk is the most acnegenic, she said.
Psoriasis
A systematic review of 55 studies evaluating diet and psoriasis found obesity can be an exacerbating factor. The strongest evidence for dietary weight reduction points to a hypocaloric diet in people with overweight or obesity, according to the review. Other evidence suggests alcohol can lower response to treatment and is linked with more severe psoriasis. Furthermore, a gluten-free diet or vitamin D supplements can help some subpopulations of people with psoriasis.
“An overwhelming majority of our psoriasis patients are vitamin D deficient,” Dr. Shi said.
The National Psoriasis Foundation (NPF) publishes dietary modification guidelines, updated as recently as November 2023. The NPF states that “there is no diet that will cure psoriatic disease, but there are many ways in which eating healthful food may lessen the severity of symptoms and play a role in lowering the likelihood of developing comorbidities.”
Healthier choices include fruits, vegetables, whole grains, and fat-free or low-fat dairy products. Include lean meats, poultry, fish, beans, eggs, and nuts. Adherence to a Mediterranean diet has been linked to a lower severity of psoriasis.
Atopic Dermatitis
Atopic dermatitis (AD) is “one of the prototypical diseases related to diet,” Dr. Shi said. A different meta-analysis looked at randomized controlled trials of synbiotics (a combination of prebiotics and probiotics) for treatment of AD.
These researchers found that synbiotics do not prevent AD, but they can help treat it in adults and children older than 1 year. In addition, synbiotics are more beneficial than probiotics in treating the condition, although there are no head-to-head comparison studies. In addition, the meta-analysis found that prebiotics alone can lower AD severity.
However, Dr. Shi said, there are no recommendations from the American Academy of Dermatology (AAD) on prebiotics or probiotics for AD, and the AAD does not recommend any supplement or essential oil for AD.
In a 2022 review, investigators ranked the efficacy of different supplements for AD based on available evidence. They found the greatest benefit associated with vitamin D supplementation, followed by vitamin E, probiotics, hemp seed oil, histidine, and oolong tea. They also noted the ‘Six Food Elimination Diet and Autoimmune Protocol’ featured the least amount of evidence to back it up.
Rosacea
Rosacea appears to be caused by “all the fun things in life” like sunlight, alcohol, chocolate, spicy foods, and caffeine, Dr. Shi said. In people with rosacea, they can cause facial flushing, edema, burning, and an inflammatory response.
Certain foods can activate skin receptors and sensory neurons, which can release neuropeptides that act on mast cells in blood that lead to flushing. The skin-gut axis may also be involved, evidence suggests. “And that is why food has a pretty profound impact on rosacea,” Dr. Shi said.
Dr. Shi reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
ORLANDO, FLORIDA — Amid all the hype, claims, and confusion, there is evidence linking some foods and drinks to an increased risk for acne, psoriasis, atopic dermatitis, rosacea, and other common skin conditions. So, what is the connection in each case? And how can people with any of these skin conditions potentially improve their health and quality of life with dietary changes?
What is clear is that there has been an explosion of interest in learning which foods can improve or worsen skin issues in recent years. It’s a good idea to familiarize yourself with the research and also to Google ‘diet’ and ‘skin’, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas for Medical Sciences, Little Rock. “As practitioners, we should be well prepared to talk about what patients want to talk about.”
Acne
One of the major areas of interest is diet and acne. “We’ve all heard sugar and dairy are bad, and the Western diet is high in sugar and dairy,” Dr. Shi said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dairy, red meat, and carbohydrates can break down into leucine, an essential amino acid found in protein. Leucine and sugar together, in turn, can produce insulin and insulin-like growth factor 1 (IGF-1), which, through different pathways, can reach the androgen receptors throughout the body, including the skin. This results in sebogenesis, lipogenesis, and keratinization, which triggers follicular inflammation and results in more of the acne-causing bacteria Cutibacterium acnes.
Milk and other dairy products also can increase IGF-1 levels, which can alter hormonal mediators and increase acne.
Not all types of dairy milk are created equal, however, when it comes to acne. Dr. Shi wondered why 2% milk has overall color and nutritional content very similar to that of whole milk. “I looked into this.” She discovered that when milk manufacturers remove the fat, they often add whey proteins to restore some nutrients. Whey protein can increase acne, Dr. Shi added.
“So, if you’re going to choose any milk to drink, I think from an acne perspective, it’s better to use whole milk. If you can get it organic, even better.” Skim milk is the most acnegenic, she said.
Psoriasis
A systematic review of 55 studies evaluating diet and psoriasis found obesity can be an exacerbating factor. The strongest evidence for dietary weight reduction points to a hypocaloric diet in people with overweight or obesity, according to the review. Other evidence suggests alcohol can lower response to treatment and is linked with more severe psoriasis. Furthermore, a gluten-free diet or vitamin D supplements can help some subpopulations of people with psoriasis.
“An overwhelming majority of our psoriasis patients are vitamin D deficient,” Dr. Shi said.
The National Psoriasis Foundation (NPF) publishes dietary modification guidelines, updated as recently as November 2023. The NPF states that “there is no diet that will cure psoriatic disease, but there are many ways in which eating healthful food may lessen the severity of symptoms and play a role in lowering the likelihood of developing comorbidities.”
Healthier choices include fruits, vegetables, whole grains, and fat-free or low-fat dairy products. Include lean meats, poultry, fish, beans, eggs, and nuts. Adherence to a Mediterranean diet has been linked to a lower severity of psoriasis.
Atopic Dermatitis
Atopic dermatitis (AD) is “one of the prototypical diseases related to diet,” Dr. Shi said. A different meta-analysis looked at randomized controlled trials of synbiotics (a combination of prebiotics and probiotics) for treatment of AD.
These researchers found that synbiotics do not prevent AD, but they can help treat it in adults and children older than 1 year. In addition, synbiotics are more beneficial than probiotics in treating the condition, although there are no head-to-head comparison studies. In addition, the meta-analysis found that prebiotics alone can lower AD severity.
However, Dr. Shi said, there are no recommendations from the American Academy of Dermatology (AAD) on prebiotics or probiotics for AD, and the AAD does not recommend any supplement or essential oil for AD.
In a 2022 review, investigators ranked the efficacy of different supplements for AD based on available evidence. They found the greatest benefit associated with vitamin D supplementation, followed by vitamin E, probiotics, hemp seed oil, histidine, and oolong tea. They also noted the ‘Six Food Elimination Diet and Autoimmune Protocol’ featured the least amount of evidence to back it up.
Rosacea
Rosacea appears to be caused by “all the fun things in life” like sunlight, alcohol, chocolate, spicy foods, and caffeine, Dr. Shi said. In people with rosacea, they can cause facial flushing, edema, burning, and an inflammatory response.
Certain foods can activate skin receptors and sensory neurons, which can release neuropeptides that act on mast cells in blood that lead to flushing. The skin-gut axis may also be involved, evidence suggests. “And that is why food has a pretty profound impact on rosacea,” Dr. Shi said.
Dr. Shi reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
With Proper Training, AI Can Be a Useful Tool in Epilepsy Management
ORLANDO — Experts shed light on the applications, benefits, and pitfalls of artificial intelligence (AI) during the Merrit-Putnam Symposium at the annual meeting of the American Epilepsy Society (AES).
In a session titled “Artificial Intelligence Fundamentals and Breakthrough Applications in Epilepsy,” University of Pittsburgh neurologist and assistant professor Wesley Kerr, MD, PhD, provided an overview of AI as well its applications in neurology. He began by addressing perhaps one of the most controversial topics regarding AI in the medical community: clinicians’ fear of being replaced by technology.
he told the audience.
To Optimize AI, Clinicians Must Lay the Proper Foundation
Dr. Kerr’s presentation focused on providing audience members with tools to help them evaluate new technologies, recognize benefits, and identify key costs and limitations associated with AI implementation and integration into clinical practice.
Before delving deeper, one must first understand basic terminology regarding AI. Without this knowledge, clinicians may inadvertently introduce bias or errata or fail to understand how to best leverage the technology to enhance the quality of the practice while improving patient outcomes.
Machine learning (ML) describes the process of using data to learn a specific task. Deep learning (DL) stacks multiple layers of ML to improve performance on the task. Lastly, generative AI generates content such as text, images, and media.
Utilizing AI effectively in clinical applications involves tapping into select features most related to prediction (for example, disease factors) and grouping features into categories based on measuring commonalities such as factor composition in a population. This information should be used in training data only.
Fully understanding ML/AI allows clinicians to use it as a diagnostic test by exploiting a combination of accuracy, sensitivity, and specificity, along with positive and negative predictive values.
Data Fidelity and Integrity Hinge on Optimal Data Inputs
In the case of epilepsy, calibration curves can provide practical guidance in terms of predicting impending seizures.
“ML/AI needs gold-standard labels for evaluation,” Dr. Kerr said. He went on to stress the importance of quality data inputs to optimize the fidelity of AI’s predictive analytics.
“If you input garbage, you’ll get garbage out,” he said. “So a lot of garbage going in means a lot of garbage out.”
Such “garbage” can result in missed or erroneous diagnoses, or even faulty predictions. Even when the data are complete, AI can draw incorrect conclusions based on trends for which it lacks proper context.
Dr. Kerr used epilepsy trends in the Black population to illustrate this problem.
“One potential bias is that AI can figure out a patient is Black without being told, and based on data that Black patients are less likely to get epilepsy surgery,” he said, “AI would say they don’t need it because they’re Black, which isn’t true.”
In other words, ML/AI can use systematic determinants of health, such as race, to learn what Dr. Kerr referred to as an “inappropriate association.”
For that reason, ML/AI users must test for bias.
Such data are often retrieved from electronic health records (EHR), which serve as an important source of data ML/AI input. Using EHR makes sense, as they are a major source of missed potential in improving prompt treatment. According to Dr. Kerr, 20% of academic neurologists’ notes miss seizure frequency, and 30% miss the age of onset.
In addition, International Classification of Diseases (ICD) codes create another hurdle depending on the type of code used. For example, epilepsy with G40 or 2 codes of R56 is reliable, while focal to bilateral versus generalized epilepsy proves more challenging.
AI Improves Efficiency in National Language Generation
Large language models (LLM) look at first drafts and can save time on formatting, image selection, and construction. Perhaps ChatGPT is the most famous LLM, but other tools in this category include Open AI and Bard. LLMs are trained on “the whole internet” and use publicly accessible text.
In these cases, prompts serve as input data. Output data are predictions of the first and subsequent words.
Many users appreciate the foundation LLMs provide in terms of facilitating and collating research and summarizing ideas. The LLM-generated text actually serves as a first draft, saving users time on more clerical tasks such as formatting, image selection, and structure. Notwithstanding, these tools still require human supervision to screen for hallucinations or to add specialized content.
“LLMs are a great starting place to save time but are loaded with errors,” Dr. Kerr said.
Even if the tools could produce error-free content, ethics still come into play when using AI-generated content without any alterations. Any ML/AI that has not been modified or supervised is considered plagiarism.
Yet, interestingly enough, Dr. Kerr found that patients respond more positively to AI than physicians when interacting.
“Patients felt that AI was more sensitive and compassionate because it was longer-winded and humans are short,” he said. He went on to argue that AI might actually prove useful in helping physicians to improve the quality of their patient interactions.
Dr. Kerr left the audience with these key takeaways:
- ML/AI is just one type of clinical tool with benefits and limitations. The technology conveys the advantages of freeing up the clinician’s time to focus on more human-centered tasks, improving clinical decisions in challenging situations, and improving efficiency.
- However, healthcare systems should understand that ML/AI is not 100% foolproof, as the software’s knowledge is limited to its training exposure, and proper use requires supervision.
ORLANDO — Experts shed light on the applications, benefits, and pitfalls of artificial intelligence (AI) during the Merrit-Putnam Symposium at the annual meeting of the American Epilepsy Society (AES).
In a session titled “Artificial Intelligence Fundamentals and Breakthrough Applications in Epilepsy,” University of Pittsburgh neurologist and assistant professor Wesley Kerr, MD, PhD, provided an overview of AI as well its applications in neurology. He began by addressing perhaps one of the most controversial topics regarding AI in the medical community: clinicians’ fear of being replaced by technology.
he told the audience.
To Optimize AI, Clinicians Must Lay the Proper Foundation
Dr. Kerr’s presentation focused on providing audience members with tools to help them evaluate new technologies, recognize benefits, and identify key costs and limitations associated with AI implementation and integration into clinical practice.
Before delving deeper, one must first understand basic terminology regarding AI. Without this knowledge, clinicians may inadvertently introduce bias or errata or fail to understand how to best leverage the technology to enhance the quality of the practice while improving patient outcomes.
Machine learning (ML) describes the process of using data to learn a specific task. Deep learning (DL) stacks multiple layers of ML to improve performance on the task. Lastly, generative AI generates content such as text, images, and media.
Utilizing AI effectively in clinical applications involves tapping into select features most related to prediction (for example, disease factors) and grouping features into categories based on measuring commonalities such as factor composition in a population. This information should be used in training data only.
Fully understanding ML/AI allows clinicians to use it as a diagnostic test by exploiting a combination of accuracy, sensitivity, and specificity, along with positive and negative predictive values.
Data Fidelity and Integrity Hinge on Optimal Data Inputs
In the case of epilepsy, calibration curves can provide practical guidance in terms of predicting impending seizures.
“ML/AI needs gold-standard labels for evaluation,” Dr. Kerr said. He went on to stress the importance of quality data inputs to optimize the fidelity of AI’s predictive analytics.
“If you input garbage, you’ll get garbage out,” he said. “So a lot of garbage going in means a lot of garbage out.”
Such “garbage” can result in missed or erroneous diagnoses, or even faulty predictions. Even when the data are complete, AI can draw incorrect conclusions based on trends for which it lacks proper context.
Dr. Kerr used epilepsy trends in the Black population to illustrate this problem.
“One potential bias is that AI can figure out a patient is Black without being told, and based on data that Black patients are less likely to get epilepsy surgery,” he said, “AI would say they don’t need it because they’re Black, which isn’t true.”
In other words, ML/AI can use systematic determinants of health, such as race, to learn what Dr. Kerr referred to as an “inappropriate association.”
For that reason, ML/AI users must test for bias.
Such data are often retrieved from electronic health records (EHR), which serve as an important source of data ML/AI input. Using EHR makes sense, as they are a major source of missed potential in improving prompt treatment. According to Dr. Kerr, 20% of academic neurologists’ notes miss seizure frequency, and 30% miss the age of onset.
In addition, International Classification of Diseases (ICD) codes create another hurdle depending on the type of code used. For example, epilepsy with G40 or 2 codes of R56 is reliable, while focal to bilateral versus generalized epilepsy proves more challenging.
AI Improves Efficiency in National Language Generation
Large language models (LLM) look at first drafts and can save time on formatting, image selection, and construction. Perhaps ChatGPT is the most famous LLM, but other tools in this category include Open AI and Bard. LLMs are trained on “the whole internet” and use publicly accessible text.
In these cases, prompts serve as input data. Output data are predictions of the first and subsequent words.
Many users appreciate the foundation LLMs provide in terms of facilitating and collating research and summarizing ideas. The LLM-generated text actually serves as a first draft, saving users time on more clerical tasks such as formatting, image selection, and structure. Notwithstanding, these tools still require human supervision to screen for hallucinations or to add specialized content.
“LLMs are a great starting place to save time but are loaded with errors,” Dr. Kerr said.
Even if the tools could produce error-free content, ethics still come into play when using AI-generated content without any alterations. Any ML/AI that has not been modified or supervised is considered plagiarism.
Yet, interestingly enough, Dr. Kerr found that patients respond more positively to AI than physicians when interacting.
“Patients felt that AI was more sensitive and compassionate because it was longer-winded and humans are short,” he said. He went on to argue that AI might actually prove useful in helping physicians to improve the quality of their patient interactions.
Dr. Kerr left the audience with these key takeaways:
- ML/AI is just one type of clinical tool with benefits and limitations. The technology conveys the advantages of freeing up the clinician’s time to focus on more human-centered tasks, improving clinical decisions in challenging situations, and improving efficiency.
- However, healthcare systems should understand that ML/AI is not 100% foolproof, as the software’s knowledge is limited to its training exposure, and proper use requires supervision.
ORLANDO — Experts shed light on the applications, benefits, and pitfalls of artificial intelligence (AI) during the Merrit-Putnam Symposium at the annual meeting of the American Epilepsy Society (AES).
In a session titled “Artificial Intelligence Fundamentals and Breakthrough Applications in Epilepsy,” University of Pittsburgh neurologist and assistant professor Wesley Kerr, MD, PhD, provided an overview of AI as well its applications in neurology. He began by addressing perhaps one of the most controversial topics regarding AI in the medical community: clinicians’ fear of being replaced by technology.
he told the audience.
To Optimize AI, Clinicians Must Lay the Proper Foundation
Dr. Kerr’s presentation focused on providing audience members with tools to help them evaluate new technologies, recognize benefits, and identify key costs and limitations associated with AI implementation and integration into clinical practice.
Before delving deeper, one must first understand basic terminology regarding AI. Without this knowledge, clinicians may inadvertently introduce bias or errata or fail to understand how to best leverage the technology to enhance the quality of the practice while improving patient outcomes.
Machine learning (ML) describes the process of using data to learn a specific task. Deep learning (DL) stacks multiple layers of ML to improve performance on the task. Lastly, generative AI generates content such as text, images, and media.
Utilizing AI effectively in clinical applications involves tapping into select features most related to prediction (for example, disease factors) and grouping features into categories based on measuring commonalities such as factor composition in a population. This information should be used in training data only.
Fully understanding ML/AI allows clinicians to use it as a diagnostic test by exploiting a combination of accuracy, sensitivity, and specificity, along with positive and negative predictive values.
Data Fidelity and Integrity Hinge on Optimal Data Inputs
In the case of epilepsy, calibration curves can provide practical guidance in terms of predicting impending seizures.
“ML/AI needs gold-standard labels for evaluation,” Dr. Kerr said. He went on to stress the importance of quality data inputs to optimize the fidelity of AI’s predictive analytics.
“If you input garbage, you’ll get garbage out,” he said. “So a lot of garbage going in means a lot of garbage out.”
Such “garbage” can result in missed or erroneous diagnoses, or even faulty predictions. Even when the data are complete, AI can draw incorrect conclusions based on trends for which it lacks proper context.
Dr. Kerr used epilepsy trends in the Black population to illustrate this problem.
“One potential bias is that AI can figure out a patient is Black without being told, and based on data that Black patients are less likely to get epilepsy surgery,” he said, “AI would say they don’t need it because they’re Black, which isn’t true.”
In other words, ML/AI can use systematic determinants of health, such as race, to learn what Dr. Kerr referred to as an “inappropriate association.”
For that reason, ML/AI users must test for bias.
Such data are often retrieved from electronic health records (EHR), which serve as an important source of data ML/AI input. Using EHR makes sense, as they are a major source of missed potential in improving prompt treatment. According to Dr. Kerr, 20% of academic neurologists’ notes miss seizure frequency, and 30% miss the age of onset.
In addition, International Classification of Diseases (ICD) codes create another hurdle depending on the type of code used. For example, epilepsy with G40 or 2 codes of R56 is reliable, while focal to bilateral versus generalized epilepsy proves more challenging.
AI Improves Efficiency in National Language Generation
Large language models (LLM) look at first drafts and can save time on formatting, image selection, and construction. Perhaps ChatGPT is the most famous LLM, but other tools in this category include Open AI and Bard. LLMs are trained on “the whole internet” and use publicly accessible text.
In these cases, prompts serve as input data. Output data are predictions of the first and subsequent words.
Many users appreciate the foundation LLMs provide in terms of facilitating and collating research and summarizing ideas. The LLM-generated text actually serves as a first draft, saving users time on more clerical tasks such as formatting, image selection, and structure. Notwithstanding, these tools still require human supervision to screen for hallucinations or to add specialized content.
“LLMs are a great starting place to save time but are loaded with errors,” Dr. Kerr said.
Even if the tools could produce error-free content, ethics still come into play when using AI-generated content without any alterations. Any ML/AI that has not been modified or supervised is considered plagiarism.
Yet, interestingly enough, Dr. Kerr found that patients respond more positively to AI than physicians when interacting.
“Patients felt that AI was more sensitive and compassionate because it was longer-winded and humans are short,” he said. He went on to argue that AI might actually prove useful in helping physicians to improve the quality of their patient interactions.
Dr. Kerr left the audience with these key takeaways:
- ML/AI is just one type of clinical tool with benefits and limitations. The technology conveys the advantages of freeing up the clinician’s time to focus on more human-centered tasks, improving clinical decisions in challenging situations, and improving efficiency.
- However, healthcare systems should understand that ML/AI is not 100% foolproof, as the software’s knowledge is limited to its training exposure, and proper use requires supervision.
FROM AES 2023
Magic Wand Initiative Empowers Dermatologists to Innovate
NEW YORK – .
The program was founded in 2013 by two Harvard Medical School dermatologists, Lilit Garibyan, MD, PhD, the program director, and her mentor R. Rox Anderson MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital (MGH), Boston. It was based on the idea that clinicians are in a unique position to identify gaps in patient care and should be active in developing medical solutions to address those gaps.
“I truly believe that if we do a better job educating, training, and empowering our clinicians to become innovators, this will benefit patients and hospitals and physicians,” Dr. Garibyan said at the 26th annual Mount Sinai Winter Symposium — Advances in Medical and Surgical Dermatology.
One of the seeds for the project was her own experience with cryolipolysis which involves topical cooling, a noninvasive method of removing subcutaneous fat for body contouring, which relies on conducting heat from subcutaneous fat across the skin and therefore, does not reach fat far from the dermis. With Dr. Anderson’s mentorship, she developed injectable cooling technology (ICT), a procedure where “ice slurry,” composed of normal saline and glycerol, is directly injected into adipose tissue, possibly leading to more efficient and effective cryolipolysis.
After nearly 10 years of animal studies at MGH, led by Dr. Garibyan as proof of concept trials, ice slurry (Coolio Therapy) recently received FDA breakthrough designation for long-term pain control and early-stage human trials of clinical applications are underway, she noted.
Magic Wand Program
In the Magic Wand program, participating physicians start by recording areas of unmet needs in their day-to-day practices, and in groups, engage in clinician-only brainstorming sessions to screen ideas, define problems, and generate lists of specifications and tools needed to address clinical problems. After working together to define challenges and possible solutions, they take their ideas to a development team, where scientists, engineers, regulatory experts, and industry professionals meet and help clinicians start pilot proof-of-concept projects, develop prototypes, and gain support for studies, followed by pilot feasibility studies.
Part of the project is the Virtual Magic Wand (VMW) Initiative, a 10-month online instructive and interactive course open to clinicians in the United States and Europe, designed to bring together dermatologists “interested in deeply understanding a dermatologic clinical problem worth solving,” according to Dr. Garibyan. Currently, there are more than 86 VMW scholars from 46 institutions, and military and private practice sites in the United States. The VMW was expanded to Europe in 2021 and there are plans to expand to Asia as well, she said.
The success of the program is not only attributed to its clinical methods but the fact that it provides a benefit to doctors at all stages of their careers, patients, and industry. “This is the only program that aims to engage in innovation from resident to full professor. We provide ideas that industry can then support and bring to market. Everyone including patients, doctors, and healthcare companies can benefit from active, engaged, and innovative physicians,” Dr. Garibyan said.
One of the success stories is that of Veradermics, a company founded by Kansas City dermatologist, Reid A. Waldman, MD, the company’s CEO, and Tim Durso, MD, the president, who met while participating in the VMW program in 2020, which eventually led them to start a company addressing an unmet need in dermatology, a kid-friendly treatment of warts.
In an interview with this news organization, Dr. Waldman explained how the program informed his company’s ethos. “Magic Wand Initiative is about identifying problems worth solving,” he said. At the company, “we find problems or unmet needs that are large enough to motivate prescribing changes, so we’ve really taken the philosophy I learned in the program into this company and building our portfolio.”
One of the first needs that Veradermics addressed was the fact that treatment for common warts, cryotherapy with liquid nitrogen, is painful and can frighten children, and, with a response rate of “at best, 50%,” Dr. Waldman said. Veradermics is in the process of creating a nearly painless, child-friendly wart treatment: an “immunostimulatory dissolvable microarray” patch that contains Candida antigen extract, which is currently being evaluated for treating warts in a phase 2 clinical trial started in 2023.
Although the Magic Wand Initiative was initially restricted to dermatologists at MGH, stories like that of Veradermics have made the program so popular that it has branched out to include anesthesiologists and otolaryngologists, as well as general and orthopedic surgeons at MGH, Dr. Garibyan said at the Mount Sinai meeting.
Dr. Garibyan disclosed that she is a cofounder of and has equity in Brixton Biosciences and EyeCool, and is a consultant for and/or investor in Brixton and Clarity Cosmetics. Royalties/inventorship are assigned to MGH.
NEW YORK – .
The program was founded in 2013 by two Harvard Medical School dermatologists, Lilit Garibyan, MD, PhD, the program director, and her mentor R. Rox Anderson MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital (MGH), Boston. It was based on the idea that clinicians are in a unique position to identify gaps in patient care and should be active in developing medical solutions to address those gaps.
“I truly believe that if we do a better job educating, training, and empowering our clinicians to become innovators, this will benefit patients and hospitals and physicians,” Dr. Garibyan said at the 26th annual Mount Sinai Winter Symposium — Advances in Medical and Surgical Dermatology.
One of the seeds for the project was her own experience with cryolipolysis which involves topical cooling, a noninvasive method of removing subcutaneous fat for body contouring, which relies on conducting heat from subcutaneous fat across the skin and therefore, does not reach fat far from the dermis. With Dr. Anderson’s mentorship, she developed injectable cooling technology (ICT), a procedure where “ice slurry,” composed of normal saline and glycerol, is directly injected into adipose tissue, possibly leading to more efficient and effective cryolipolysis.
After nearly 10 years of animal studies at MGH, led by Dr. Garibyan as proof of concept trials, ice slurry (Coolio Therapy) recently received FDA breakthrough designation for long-term pain control and early-stage human trials of clinical applications are underway, she noted.
Magic Wand Program
In the Magic Wand program, participating physicians start by recording areas of unmet needs in their day-to-day practices, and in groups, engage in clinician-only brainstorming sessions to screen ideas, define problems, and generate lists of specifications and tools needed to address clinical problems. After working together to define challenges and possible solutions, they take their ideas to a development team, where scientists, engineers, regulatory experts, and industry professionals meet and help clinicians start pilot proof-of-concept projects, develop prototypes, and gain support for studies, followed by pilot feasibility studies.
Part of the project is the Virtual Magic Wand (VMW) Initiative, a 10-month online instructive and interactive course open to clinicians in the United States and Europe, designed to bring together dermatologists “interested in deeply understanding a dermatologic clinical problem worth solving,” according to Dr. Garibyan. Currently, there are more than 86 VMW scholars from 46 institutions, and military and private practice sites in the United States. The VMW was expanded to Europe in 2021 and there are plans to expand to Asia as well, she said.
The success of the program is not only attributed to its clinical methods but the fact that it provides a benefit to doctors at all stages of their careers, patients, and industry. “This is the only program that aims to engage in innovation from resident to full professor. We provide ideas that industry can then support and bring to market. Everyone including patients, doctors, and healthcare companies can benefit from active, engaged, and innovative physicians,” Dr. Garibyan said.
One of the success stories is that of Veradermics, a company founded by Kansas City dermatologist, Reid A. Waldman, MD, the company’s CEO, and Tim Durso, MD, the president, who met while participating in the VMW program in 2020, which eventually led them to start a company addressing an unmet need in dermatology, a kid-friendly treatment of warts.
In an interview with this news organization, Dr. Waldman explained how the program informed his company’s ethos. “Magic Wand Initiative is about identifying problems worth solving,” he said. At the company, “we find problems or unmet needs that are large enough to motivate prescribing changes, so we’ve really taken the philosophy I learned in the program into this company and building our portfolio.”
One of the first needs that Veradermics addressed was the fact that treatment for common warts, cryotherapy with liquid nitrogen, is painful and can frighten children, and, with a response rate of “at best, 50%,” Dr. Waldman said. Veradermics is in the process of creating a nearly painless, child-friendly wart treatment: an “immunostimulatory dissolvable microarray” patch that contains Candida antigen extract, which is currently being evaluated for treating warts in a phase 2 clinical trial started in 2023.
Although the Magic Wand Initiative was initially restricted to dermatologists at MGH, stories like that of Veradermics have made the program so popular that it has branched out to include anesthesiologists and otolaryngologists, as well as general and orthopedic surgeons at MGH, Dr. Garibyan said at the Mount Sinai meeting.
Dr. Garibyan disclosed that she is a cofounder of and has equity in Brixton Biosciences and EyeCool, and is a consultant for and/or investor in Brixton and Clarity Cosmetics. Royalties/inventorship are assigned to MGH.
NEW YORK – .
The program was founded in 2013 by two Harvard Medical School dermatologists, Lilit Garibyan, MD, PhD, the program director, and her mentor R. Rox Anderson MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital (MGH), Boston. It was based on the idea that clinicians are in a unique position to identify gaps in patient care and should be active in developing medical solutions to address those gaps.
“I truly believe that if we do a better job educating, training, and empowering our clinicians to become innovators, this will benefit patients and hospitals and physicians,” Dr. Garibyan said at the 26th annual Mount Sinai Winter Symposium — Advances in Medical and Surgical Dermatology.
One of the seeds for the project was her own experience with cryolipolysis which involves topical cooling, a noninvasive method of removing subcutaneous fat for body contouring, which relies on conducting heat from subcutaneous fat across the skin and therefore, does not reach fat far from the dermis. With Dr. Anderson’s mentorship, she developed injectable cooling technology (ICT), a procedure where “ice slurry,” composed of normal saline and glycerol, is directly injected into adipose tissue, possibly leading to more efficient and effective cryolipolysis.
After nearly 10 years of animal studies at MGH, led by Dr. Garibyan as proof of concept trials, ice slurry (Coolio Therapy) recently received FDA breakthrough designation for long-term pain control and early-stage human trials of clinical applications are underway, she noted.
Magic Wand Program
In the Magic Wand program, participating physicians start by recording areas of unmet needs in their day-to-day practices, and in groups, engage in clinician-only brainstorming sessions to screen ideas, define problems, and generate lists of specifications and tools needed to address clinical problems. After working together to define challenges and possible solutions, they take their ideas to a development team, where scientists, engineers, regulatory experts, and industry professionals meet and help clinicians start pilot proof-of-concept projects, develop prototypes, and gain support for studies, followed by pilot feasibility studies.
Part of the project is the Virtual Magic Wand (VMW) Initiative, a 10-month online instructive and interactive course open to clinicians in the United States and Europe, designed to bring together dermatologists “interested in deeply understanding a dermatologic clinical problem worth solving,” according to Dr. Garibyan. Currently, there are more than 86 VMW scholars from 46 institutions, and military and private practice sites in the United States. The VMW was expanded to Europe in 2021 and there are plans to expand to Asia as well, she said.
The success of the program is not only attributed to its clinical methods but the fact that it provides a benefit to doctors at all stages of their careers, patients, and industry. “This is the only program that aims to engage in innovation from resident to full professor. We provide ideas that industry can then support and bring to market. Everyone including patients, doctors, and healthcare companies can benefit from active, engaged, and innovative physicians,” Dr. Garibyan said.
One of the success stories is that of Veradermics, a company founded by Kansas City dermatologist, Reid A. Waldman, MD, the company’s CEO, and Tim Durso, MD, the president, who met while participating in the VMW program in 2020, which eventually led them to start a company addressing an unmet need in dermatology, a kid-friendly treatment of warts.
In an interview with this news organization, Dr. Waldman explained how the program informed his company’s ethos. “Magic Wand Initiative is about identifying problems worth solving,” he said. At the company, “we find problems or unmet needs that are large enough to motivate prescribing changes, so we’ve really taken the philosophy I learned in the program into this company and building our portfolio.”
One of the first needs that Veradermics addressed was the fact that treatment for common warts, cryotherapy with liquid nitrogen, is painful and can frighten children, and, with a response rate of “at best, 50%,” Dr. Waldman said. Veradermics is in the process of creating a nearly painless, child-friendly wart treatment: an “immunostimulatory dissolvable microarray” patch that contains Candida antigen extract, which is currently being evaluated for treating warts in a phase 2 clinical trial started in 2023.
Although the Magic Wand Initiative was initially restricted to dermatologists at MGH, stories like that of Veradermics have made the program so popular that it has branched out to include anesthesiologists and otolaryngologists, as well as general and orthopedic surgeons at MGH, Dr. Garibyan said at the Mount Sinai meeting.
Dr. Garibyan disclosed that she is a cofounder of and has equity in Brixton Biosciences and EyeCool, and is a consultant for and/or investor in Brixton and Clarity Cosmetics. Royalties/inventorship are assigned to MGH.
BC axillary dissection may be unnecessary for isolated tumor cells after NAC
SAN ANTONIO — Axillary lymph node dissection is the current standard of care in breast cancer when metastases are found in sentinel lymph nodes after neoadjuvant chemotherapy.
However, what to do when isolated tumor cells instead of outright metastases are found in sentinel nodes is an open question. Some surgeons opt for a full axillary dissection while others do not, and there is no standard of care, explained Giacomo Montagna, MD, a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York City.
The study led and presented by Dr. Montagna at the San Antonio Breast Cancer Symposium brings some much-needed clarity to the issue.
The findings argue strongly against “routine axillary lymph node dissection” — with its considerable morbidities — “in patients with residual isolated tumor cells after neoadjuvant chemotherapy,” Dr. Montagna said.
Study discussant Elizabeth Mittendorf, MD, PhD, a breast cancer surgeon at Brigham and Women’s Hospital, Boston, agreed.
“It appears that the presence of isolated tumor cells in the sentinel nodes does not negatively impact oncologic outcomes. These additional data allow us to debunk some of the surgical dogma we grew up with, specifically that lymph node dissection is required for either survival or local control,” Dr. Mittendorf said.
However, there was concern among audience members that the information gleaned from a full dissection might still be needed to guide follow-on adjuvant therapy decisions.
Dr. Mittendorf didn’t think so. Although additional positive lymph nodes were found in almost a third of women who had axillary dissections in the review, the majority of involved nodes simply had more isolated tumor cells; macrometastases were found in just 5% of cases.
So, for most patients, additional information from axillary dissections is “unlikely needed to inform adjuvant therapy, and in fact,” based on the 5% figure, “we are thinking we would have to do well over a hundred lymph node dissections in such patients to inform treatment recommendations for fewer than five. This comes at the cost of fair morbidity,” she said.
Study details
The retrospective study, dubbed OPBC05/EUBREAST-14R/ICARO, included 583 women with cT1-4 N0-3 breast cancer treated at 62 centers in 18 countries. The majority of subjects were from the United States and Europe.
Every patient was found to have isolated tumor cells (ITCs) in their sentinel lymph nodes after neoadjuvant chemotherapy (NAC), which generally included anthracycline and taxane-based regimens. The majority of patients did not have a pathologic complete response to NAC.
Overall, 182 patients (31%) had a subsequent axillary lymph node dissection; the rest did not.
Dissections were more common in the presence of lymphovascular invasion and N2/N3 disease as well as when fewer lymph nodes were removed and when ITCs were found during surgery on frozen section, which was the case in a quarter of patients.
Additional positive nodes were found in 30% of patients in the dissection group and consisted of more nodes with ITCs in 18%, micrometastases in 7%, and macrometastases in 5%. Receptor status and nodal status at presentation did not have an impact on the likelihood of finding macrometastases.
The main finding of the study was that there were no statistically significant differences in recurrence outcomes between the two groups.
The 5-year rate of isolated axillary recurrence was 1.7% with axillary lymph node dissection (ALND) versus 1.1% without it. The 5-year rate of any invasive recurrence was 16% in the ALND arm and 19% in the no-dissection group.
The median age in the study was 48 years. The majority of patients (57%) had clinical T2 tumors. Most were HR positive and either HER2 negative (41%) or HER2 positive (28%).
Regional nodal radiation was more common in the ALND group, 82% versus 75%. The dissection arm had a mean of 2.8 sentinel lymph nodes removed versus 3.5 in the no-dissection group.
“The likelihood of finding additional positive lymph nodes in patients with residual ITCs after NAC is lower than in patients with residual micro- and macrometastases. In the majority of cases, they contain ITCs. Nodal recurrence after omission of ALND is rare in this population,” the investigators concluded in their abstract.
The work was funded by EUBREAST. Dr. Montagna doesn’t have any disclosures. Dr. Mittendorf has several industry ties, including being an advisor for Roche, AstraZeneca, and Moderna and a speaker for Merck.
SAN ANTONIO — Axillary lymph node dissection is the current standard of care in breast cancer when metastases are found in sentinel lymph nodes after neoadjuvant chemotherapy.
However, what to do when isolated tumor cells instead of outright metastases are found in sentinel nodes is an open question. Some surgeons opt for a full axillary dissection while others do not, and there is no standard of care, explained Giacomo Montagna, MD, a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York City.
The study led and presented by Dr. Montagna at the San Antonio Breast Cancer Symposium brings some much-needed clarity to the issue.
The findings argue strongly against “routine axillary lymph node dissection” — with its considerable morbidities — “in patients with residual isolated tumor cells after neoadjuvant chemotherapy,” Dr. Montagna said.
Study discussant Elizabeth Mittendorf, MD, PhD, a breast cancer surgeon at Brigham and Women’s Hospital, Boston, agreed.
“It appears that the presence of isolated tumor cells in the sentinel nodes does not negatively impact oncologic outcomes. These additional data allow us to debunk some of the surgical dogma we grew up with, specifically that lymph node dissection is required for either survival or local control,” Dr. Mittendorf said.
However, there was concern among audience members that the information gleaned from a full dissection might still be needed to guide follow-on adjuvant therapy decisions.
Dr. Mittendorf didn’t think so. Although additional positive lymph nodes were found in almost a third of women who had axillary dissections in the review, the majority of involved nodes simply had more isolated tumor cells; macrometastases were found in just 5% of cases.
So, for most patients, additional information from axillary dissections is “unlikely needed to inform adjuvant therapy, and in fact,” based on the 5% figure, “we are thinking we would have to do well over a hundred lymph node dissections in such patients to inform treatment recommendations for fewer than five. This comes at the cost of fair morbidity,” she said.
Study details
The retrospective study, dubbed OPBC05/EUBREAST-14R/ICARO, included 583 women with cT1-4 N0-3 breast cancer treated at 62 centers in 18 countries. The majority of subjects were from the United States and Europe.
Every patient was found to have isolated tumor cells (ITCs) in their sentinel lymph nodes after neoadjuvant chemotherapy (NAC), which generally included anthracycline and taxane-based regimens. The majority of patients did not have a pathologic complete response to NAC.
Overall, 182 patients (31%) had a subsequent axillary lymph node dissection; the rest did not.
Dissections were more common in the presence of lymphovascular invasion and N2/N3 disease as well as when fewer lymph nodes were removed and when ITCs were found during surgery on frozen section, which was the case in a quarter of patients.
Additional positive nodes were found in 30% of patients in the dissection group and consisted of more nodes with ITCs in 18%, micrometastases in 7%, and macrometastases in 5%. Receptor status and nodal status at presentation did not have an impact on the likelihood of finding macrometastases.
The main finding of the study was that there were no statistically significant differences in recurrence outcomes between the two groups.
The 5-year rate of isolated axillary recurrence was 1.7% with axillary lymph node dissection (ALND) versus 1.1% without it. The 5-year rate of any invasive recurrence was 16% in the ALND arm and 19% in the no-dissection group.
The median age in the study was 48 years. The majority of patients (57%) had clinical T2 tumors. Most were HR positive and either HER2 negative (41%) or HER2 positive (28%).
Regional nodal radiation was more common in the ALND group, 82% versus 75%. The dissection arm had a mean of 2.8 sentinel lymph nodes removed versus 3.5 in the no-dissection group.
“The likelihood of finding additional positive lymph nodes in patients with residual ITCs after NAC is lower than in patients with residual micro- and macrometastases. In the majority of cases, they contain ITCs. Nodal recurrence after omission of ALND is rare in this population,” the investigators concluded in their abstract.
The work was funded by EUBREAST. Dr. Montagna doesn’t have any disclosures. Dr. Mittendorf has several industry ties, including being an advisor for Roche, AstraZeneca, and Moderna and a speaker for Merck.
SAN ANTONIO — Axillary lymph node dissection is the current standard of care in breast cancer when metastases are found in sentinel lymph nodes after neoadjuvant chemotherapy.
However, what to do when isolated tumor cells instead of outright metastases are found in sentinel nodes is an open question. Some surgeons opt for a full axillary dissection while others do not, and there is no standard of care, explained Giacomo Montagna, MD, a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York City.
The study led and presented by Dr. Montagna at the San Antonio Breast Cancer Symposium brings some much-needed clarity to the issue.
The findings argue strongly against “routine axillary lymph node dissection” — with its considerable morbidities — “in patients with residual isolated tumor cells after neoadjuvant chemotherapy,” Dr. Montagna said.
Study discussant Elizabeth Mittendorf, MD, PhD, a breast cancer surgeon at Brigham and Women’s Hospital, Boston, agreed.
“It appears that the presence of isolated tumor cells in the sentinel nodes does not negatively impact oncologic outcomes. These additional data allow us to debunk some of the surgical dogma we grew up with, specifically that lymph node dissection is required for either survival or local control,” Dr. Mittendorf said.
However, there was concern among audience members that the information gleaned from a full dissection might still be needed to guide follow-on adjuvant therapy decisions.
Dr. Mittendorf didn’t think so. Although additional positive lymph nodes were found in almost a third of women who had axillary dissections in the review, the majority of involved nodes simply had more isolated tumor cells; macrometastases were found in just 5% of cases.
So, for most patients, additional information from axillary dissections is “unlikely needed to inform adjuvant therapy, and in fact,” based on the 5% figure, “we are thinking we would have to do well over a hundred lymph node dissections in such patients to inform treatment recommendations for fewer than five. This comes at the cost of fair morbidity,” she said.
Study details
The retrospective study, dubbed OPBC05/EUBREAST-14R/ICARO, included 583 women with cT1-4 N0-3 breast cancer treated at 62 centers in 18 countries. The majority of subjects were from the United States and Europe.
Every patient was found to have isolated tumor cells (ITCs) in their sentinel lymph nodes after neoadjuvant chemotherapy (NAC), which generally included anthracycline and taxane-based regimens. The majority of patients did not have a pathologic complete response to NAC.
Overall, 182 patients (31%) had a subsequent axillary lymph node dissection; the rest did not.
Dissections were more common in the presence of lymphovascular invasion and N2/N3 disease as well as when fewer lymph nodes were removed and when ITCs were found during surgery on frozen section, which was the case in a quarter of patients.
Additional positive nodes were found in 30% of patients in the dissection group and consisted of more nodes with ITCs in 18%, micrometastases in 7%, and macrometastases in 5%. Receptor status and nodal status at presentation did not have an impact on the likelihood of finding macrometastases.
The main finding of the study was that there were no statistically significant differences in recurrence outcomes between the two groups.
The 5-year rate of isolated axillary recurrence was 1.7% with axillary lymph node dissection (ALND) versus 1.1% without it. The 5-year rate of any invasive recurrence was 16% in the ALND arm and 19% in the no-dissection group.
The median age in the study was 48 years. The majority of patients (57%) had clinical T2 tumors. Most were HR positive and either HER2 negative (41%) or HER2 positive (28%).
Regional nodal radiation was more common in the ALND group, 82% versus 75%. The dissection arm had a mean of 2.8 sentinel lymph nodes removed versus 3.5 in the no-dissection group.
“The likelihood of finding additional positive lymph nodes in patients with residual ITCs after NAC is lower than in patients with residual micro- and macrometastases. In the majority of cases, they contain ITCs. Nodal recurrence after omission of ALND is rare in this population,” the investigators concluded in their abstract.
The work was funded by EUBREAST. Dr. Montagna doesn’t have any disclosures. Dr. Mittendorf has several industry ties, including being an advisor for Roche, AstraZeneca, and Moderna and a speaker for Merck.
AT SABCS 2023
Genetic Testing Is Recommended for Adult Patients With Epilepsy
ORLANDO — The epilepsy community has yet to come to a consensus on genetic testing. During a session at the annual meeting of the American Epilepsy Society (AES), researchers and clinicians convened to share their insights on genetic testing of adult patients with epilepsy.
Colin Ellis, MD, assistant professor of neurology at the Hospital of the University of Pennsylvania in Philadelphia, shared his clinical experience to explain the importance of genetic testing in adults patients despite access challenges, limited information on certain variants, and physician reticence.
“There’s a false misconception that genetic testing should only apply to children,” Dr. Ellis told the audience. “The earlier the onset of seizures, the more likely you are to find a genetic cause.”
Guidelines Differ
The International League Against Epilepsy Task Force for Clinical Genetic Testing, Development and Epileptic Encephalopathies (DEE) recommends conducting genetic testing in patients who have focal or generalized epilepsies to whom the following circumstances apply: autism or dysmorphism, familial history, or drug-resistant epilepsy.
However, the National Society of Genetic Counselors’ guidelines recommends genetic testing for patients who have any unexplained or idiopathic epilepsies.
Guidelines identify the patients who should get tested regardless of their age.
Personal Experience
Dr. Ellis, who has spent nearly 5 years running tests on patients with epilepsy, recently tested the 300th patient at his clinic. According to him, the yield is higher in focal epilepsy than in general epilepsy — an occurrence that counters what many believe.
“Focal epilepsies are more common than monogenic epilepsies but not intuitive to many people in the industry, despite being stated in the literature,” he said. “The absence of family history shouldn’t preclude you from genetic testing because it’s still possible to have a de novo variant not inherited from either parent.”
Genetic testing can be conducted by interrogating either the exome or the genome. However, cost remains a major barrier to access.
Dr. Ellis made several arguments supporting the use of genetic testing. First, genetic testing allows for a higher diagnostic yield (i.e., 24% versus 19% in panels and 9% in microarrays). Genetic testing provides a more comprehensive overview of a patient’s genetic landscape, and it can enhance the ability to identify certain epileptic conditions, such as those caused by monogenic epilepsy — a condition associated with 926 different genes.
“You’re also less likely to find variants of uncertain significance (VUS),” Dr. Ellis said. “Regardless, you should provide the lab with phenotype information because it will help them help you.”
Variants of Uncertain Significance
The National Human Genome Research Institute defines VUS as a variant found in a patient’s genome for which it remains unclear as to whether a health condition is causing the variant. Oftentimes, such variants have very little information available due to their rarity.
In order to resolve VUS, Dr. Ellis recommended family segregation. “If the VUS appears to be de novo, you should test the parent because if they carry the gene, then it’s probably not the cause,” he said.
Dr. Ellis outlined several steps in resolving VUS.
For starters, clinicians should determine the phenotypic fit and run some ancillary tests. For example, in the case of Glu 1 abnormalities, one should consider conducting a spinal tap to determine whether the patient has cerebral spinal fluid before taking additional action.
In addition, Dr. Ellis recommends defining variant characteristics, as it becomes important in determining whether it is appropriate to take action because the majority of variances are benign.
“The take-home point is that you should not act clinically on a VUS unless you know what you’re doing,” he said. “I also disagree with the belief that VUS are rare — it’s just that they cause so much anxiety because we’re uncomfortable with this kind of testing.”
ORLANDO — The epilepsy community has yet to come to a consensus on genetic testing. During a session at the annual meeting of the American Epilepsy Society (AES), researchers and clinicians convened to share their insights on genetic testing of adult patients with epilepsy.
Colin Ellis, MD, assistant professor of neurology at the Hospital of the University of Pennsylvania in Philadelphia, shared his clinical experience to explain the importance of genetic testing in adults patients despite access challenges, limited information on certain variants, and physician reticence.
“There’s a false misconception that genetic testing should only apply to children,” Dr. Ellis told the audience. “The earlier the onset of seizures, the more likely you are to find a genetic cause.”
Guidelines Differ
The International League Against Epilepsy Task Force for Clinical Genetic Testing, Development and Epileptic Encephalopathies (DEE) recommends conducting genetic testing in patients who have focal or generalized epilepsies to whom the following circumstances apply: autism or dysmorphism, familial history, or drug-resistant epilepsy.
However, the National Society of Genetic Counselors’ guidelines recommends genetic testing for patients who have any unexplained or idiopathic epilepsies.
Guidelines identify the patients who should get tested regardless of their age.
Personal Experience
Dr. Ellis, who has spent nearly 5 years running tests on patients with epilepsy, recently tested the 300th patient at his clinic. According to him, the yield is higher in focal epilepsy than in general epilepsy — an occurrence that counters what many believe.
“Focal epilepsies are more common than monogenic epilepsies but not intuitive to many people in the industry, despite being stated in the literature,” he said. “The absence of family history shouldn’t preclude you from genetic testing because it’s still possible to have a de novo variant not inherited from either parent.”
Genetic testing can be conducted by interrogating either the exome or the genome. However, cost remains a major barrier to access.
Dr. Ellis made several arguments supporting the use of genetic testing. First, genetic testing allows for a higher diagnostic yield (i.e., 24% versus 19% in panels and 9% in microarrays). Genetic testing provides a more comprehensive overview of a patient’s genetic landscape, and it can enhance the ability to identify certain epileptic conditions, such as those caused by monogenic epilepsy — a condition associated with 926 different genes.
“You’re also less likely to find variants of uncertain significance (VUS),” Dr. Ellis said. “Regardless, you should provide the lab with phenotype information because it will help them help you.”
Variants of Uncertain Significance
The National Human Genome Research Institute defines VUS as a variant found in a patient’s genome for which it remains unclear as to whether a health condition is causing the variant. Oftentimes, such variants have very little information available due to their rarity.
In order to resolve VUS, Dr. Ellis recommended family segregation. “If the VUS appears to be de novo, you should test the parent because if they carry the gene, then it’s probably not the cause,” he said.
Dr. Ellis outlined several steps in resolving VUS.
For starters, clinicians should determine the phenotypic fit and run some ancillary tests. For example, in the case of Glu 1 abnormalities, one should consider conducting a spinal tap to determine whether the patient has cerebral spinal fluid before taking additional action.
In addition, Dr. Ellis recommends defining variant characteristics, as it becomes important in determining whether it is appropriate to take action because the majority of variances are benign.
“The take-home point is that you should not act clinically on a VUS unless you know what you’re doing,” he said. “I also disagree with the belief that VUS are rare — it’s just that they cause so much anxiety because we’re uncomfortable with this kind of testing.”
ORLANDO — The epilepsy community has yet to come to a consensus on genetic testing. During a session at the annual meeting of the American Epilepsy Society (AES), researchers and clinicians convened to share their insights on genetic testing of adult patients with epilepsy.
Colin Ellis, MD, assistant professor of neurology at the Hospital of the University of Pennsylvania in Philadelphia, shared his clinical experience to explain the importance of genetic testing in adults patients despite access challenges, limited information on certain variants, and physician reticence.
“There’s a false misconception that genetic testing should only apply to children,” Dr. Ellis told the audience. “The earlier the onset of seizures, the more likely you are to find a genetic cause.”
Guidelines Differ
The International League Against Epilepsy Task Force for Clinical Genetic Testing, Development and Epileptic Encephalopathies (DEE) recommends conducting genetic testing in patients who have focal or generalized epilepsies to whom the following circumstances apply: autism or dysmorphism, familial history, or drug-resistant epilepsy.
However, the National Society of Genetic Counselors’ guidelines recommends genetic testing for patients who have any unexplained or idiopathic epilepsies.
Guidelines identify the patients who should get tested regardless of their age.
Personal Experience
Dr. Ellis, who has spent nearly 5 years running tests on patients with epilepsy, recently tested the 300th patient at his clinic. According to him, the yield is higher in focal epilepsy than in general epilepsy — an occurrence that counters what many believe.
“Focal epilepsies are more common than monogenic epilepsies but not intuitive to many people in the industry, despite being stated in the literature,” he said. “The absence of family history shouldn’t preclude you from genetic testing because it’s still possible to have a de novo variant not inherited from either parent.”
Genetic testing can be conducted by interrogating either the exome or the genome. However, cost remains a major barrier to access.
Dr. Ellis made several arguments supporting the use of genetic testing. First, genetic testing allows for a higher diagnostic yield (i.e., 24% versus 19% in panels and 9% in microarrays). Genetic testing provides a more comprehensive overview of a patient’s genetic landscape, and it can enhance the ability to identify certain epileptic conditions, such as those caused by monogenic epilepsy — a condition associated with 926 different genes.
“You’re also less likely to find variants of uncertain significance (VUS),” Dr. Ellis said. “Regardless, you should provide the lab with phenotype information because it will help them help you.”
Variants of Uncertain Significance
The National Human Genome Research Institute defines VUS as a variant found in a patient’s genome for which it remains unclear as to whether a health condition is causing the variant. Oftentimes, such variants have very little information available due to their rarity.
In order to resolve VUS, Dr. Ellis recommended family segregation. “If the VUS appears to be de novo, you should test the parent because if they carry the gene, then it’s probably not the cause,” he said.
Dr. Ellis outlined several steps in resolving VUS.
For starters, clinicians should determine the phenotypic fit and run some ancillary tests. For example, in the case of Glu 1 abnormalities, one should consider conducting a spinal tap to determine whether the patient has cerebral spinal fluid before taking additional action.
In addition, Dr. Ellis recommends defining variant characteristics, as it becomes important in determining whether it is appropriate to take action because the majority of variances are benign.
“The take-home point is that you should not act clinically on a VUS unless you know what you’re doing,” he said. “I also disagree with the belief that VUS are rare — it’s just that they cause so much anxiety because we’re uncomfortable with this kind of testing.”
FROM AES 2023
Gestational Diabetes Treatment Moves Forward With Uncertainty And Hope
FAIRFAX, VIRGINIA — , but researchers at the biennial meeting of the Diabetes in Pregnancy Study Group of North America expressed hope for more clarity in the near future and the ability to someday individualize treatment to account for what is increasingly viewed as a heterogeneous condition.
Until studies in 2015 and 2018 cast doubt on glyburide, “we used to have 80% [of our GDM patients] on glyburide, and 20% on insulin,” Maisa Feghali, MD, of the University of Pittsburgh, said during a discussion period. “Now we have 95% on insulin and 5% on oral hypoglycemics. I rely on insulin because I don’t have a better option, and I rely on research efforts [underway to provide better options]” in the future.
The American College of Obstetricians and Gynecologists recommends insulin as the preferred first-line pharmacologic therapy for GDM when pharmacologic therapy is needed, with metformin as an option when patients decline or cannot safely use insulin. Glyburide, ACOG said in its 2018 practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64), should not be recommended as a first-line pharmacologic therapy.
The Society of Maternal-Fetal Medicine, on the other hand, has accepted metformin as a “reasonable and safe” first-line alternative to insulin — while recognizing that half of women will still require insulin to achieve glycemic control — and does not rule out consideration of glyburide. In its 2018 statement on the pharmacologic treatment of GDM, the society said that the evidence of benefit of one oral agent over another remains limited.
“When you have dueling guidelines, it means the data are not that clear,” George Saade, MD, professor and chair of obstetrics and gynecology at the Eastern Virginia School of Medicine, Norfolk, said in a presentation on GDM. An upcoming $12 million multicenter study to be led by the Ohio State University College of Medicine — coined the DECIDE trial — should provide clarity, he said.
The trial, funded by the Patient-Centered Outcomes Research Institute, which funds comparative clinical effectiveness research designed to be broadly applicable to practice, will enroll and randomize over 1500 pregnant individuals with GDM to either oral metformin or insulin and will follow mothers and children until 2 years after delivery.
The study’s primary and secondary hypotheses, respectively, are that metformin is not inferior to insulin in reducing a composite adverse neonatal outcome (large for gestational age, neonatal hypoglycemia and/or hyperbilirubemia) and that metformin does not result in increased child body mass index at 2 years, compared with insulin. It will also look at patient-reported factors associated with metformin use compared to insulin use — factors that “are important ... to enable clinical implementation of study findings,” said Dr. Saade, who played a role in designing the study over the past several years.
The study will take a pragmatic, real-world approach by ensuring racial and ethnic, socioeconomic, urban and rural, and geographic diversity at both large academic and community-based sites across the United States.
The trial, to be led by Mark Landon, MD, and Kartik Venkatesh, MD, PhD, of Ohio State University, will be the first large trial in the United States to both directly compare the ability of oral hypoglycemics and insulin to prevent GDM-associated pregnancy complications, and to follow children for 2 years, Dr. Saade said. “Prior research was either outside the United States, not randomized, not adequately powered, or had no long-term child follow-up,” he added after the meeting.
The State Of Knowledge About Oral Hypoglycemics
The trial was envisioned several years ago as a three-arm comparative trial including the sulfonylurea glyburide, but data published in recent years has increasingly “not favored” glyburide, and many providers “have stopped using it,” Dr. Saade said during and after the meeting. At this point, “it would not be useful to include it” in a pragmatic trial, he said.
Glyburide became the number one agent after a seminal trial published in 2000 (N Engl J Med. 2000;343:1134-8) showed equivalent glycemic control in about 400 women with GDM who were randomized to receive insulin or glyburide. While the trial was not powered to evaluate other outcomes, there were no significant differences in neonatal complications.
In 2015, a large retrospective population-based study (JAMA Pediatr. 2015;169[5]:452-8) of more than 9,000 women with GDM showed higher risks of neonatal intensive care admission, neonatal hypoglycemia, and large-for-gestational age with glyburide compared with insulin. “It prompted a pause in thinking,” Dr. Saade recalled at the DPSG meeting. After that, several meta-analyses/systematic reviews compared the two treatments, showing varying and sometimes conflicting degrees of difference in neonatal outcomes.
In 2018, a French noninferiority randomized controlled trial (JAMA 2018;319[17]:1773-80) did not show that glyburide is not inferior to insulin in the prevention of perinatal outcomes (macrosomia, neonatal hypoglycemia, and hyperbilirubinemia). “If you add this trial to the systematic reviews, it would probably would shift more in favor of insulin,” Dr. Saade said, noting that the trial’s supplementary data included a higher rate of maternal hypoglycemia with glyburide. “I feel personally now, with all the data, that glyburide is inferior to insulin.”
A 2021 network meta-analysis (BMC Endocr Disord. 2021;21:199) that looked at glycemic control and neonatal outcomes in GDM treated with glyburide, metformin, or insulin, also offers valuable insight, Dr. Saade said. The meta-analysis used a Bayesian framework and presents results as a ranking estimated probability of a treatment being the best or worst — or in between — for different outcomes (glycemic control and neonatal outcomes), which “is one of the best ways to look at data these days,” he said.
“It tells us how likely [it is for one agent] to be better than others. Will it work most of the time? More than 60% of the time?” Dr. Saade explained. For example, the analysis “tell us that for large for gestational age, glyburide has a 94% chance of being the worst, metformin has an 80% change of being the best, and insulin a 76% chance of being in between.”
Overall, the 2021 analysis suggests that “glyburide is the most likely to be worst in most outcomes and that there is equipoise between metformin and insulin,” he said.
Meta-analyses of pharmacologic treatment of GDM have been challenged, he said, by inconsistent reporting in trials of GDM diagnostic criteria, severity of hyperglycemia, and small sample sizes (and wide confidence intervals). Criteria for supplemental insulin are also often “unclear” in trials, Dr. Saade said, as is involvement of social determinants of health and the “care package” enveloping pharmacologic interventions.
Dr. Saade, Dr. Landon, and other researchers have also lamented over the years that there is limited long-term follow-up of exposed offspring.
The Challenge of Heterogeneity
In another presentation on GDM, Maisa Feghali, MD, MS, emphasized that GDM is a heterogeneous condition, with clinical hyperglycemia not capturing individual variation in underlying physiologic processes. A 2016 study (Diabetes Care. 2016;39[6]:1052-5) assessing insulin sensitivity and secretion in 800-plus women at 24-30 weeks’ gestation found that about 50% of those with GDM had predominant insulin resistance, 30% had predominant insulin secretion deficit, and 20% were mixed.
Those with predominant insulin resistance had higher BMI, higher fasting glucose, larger infants, and greater risk of GDM-associated adverse outcomes, “suggesting that the risk is not universal or equivalent,” said Dr. Feghali, assistant professor in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh and the UPCM Magee-Women’s Hospital.
A 2019 multicenter European study (Diabetologia. 2019;62[11]:2118-28) found an even higher proportion of GDM involving predominant insulin resistance and, similarly, a greater risk of adverse pregnancy outcomes in these women than in insulin-sensitive women with GDM, “again suggesting that there’s probably some benefit to looking deeper at physiology to understand individual risk,” she said.
Research published decades ago showed that insulin sensitivity decreases by over 50% during pregnancy, and “what we’ve come to recognize is there [can be] insulin secretion deficiency that’s not able to surmount or overcome the insulin resistance that develops during advanced gestation,” she said. “We need to think not at the population level but at the individual level.”
Dr. Feghali is leading the MATCh-GDM (Metabolic Analysis for Treatment Choice in GDM) study, which has been randomizing women to receive either usual, unmatched treatment or treatment matched to GDM mechanism — metformin for predominant insulin resistance, glyburide, or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. Data are not available yet.
There is still more to be learned about the pharmacologic effects of oral hypoglycemics, she noted, pointing to a 2020 study (Clin Pharmacol Ther. 2020;107[6]:1362-72) that randomized women to glyburide, metformin, or glyburide/metformin combination therapy and measured insulin sensitivity, beta-cell responsivity, and disposition index. (The latter describes the overall metabolic state and is a product of insulin sensitivity and total beta-cell responsivity.)
“Somewhat surprisingly, they found metformin performed better than glyburide,” shifting the overall disposition index closer to normal, Dr. Feghali said. “But not surprisingly, they found the combination worked best.”
Total beta-cell responsivity occurred in 56% of the glyburide group and 74% of the combination group. Improvements in insulin sensitivity occurred in 84% of the metformin group and 74% of the combination group. Surprisingly, there was “a decrease in first-phase insulin secretion” with glyburide, noted Dr. Feghali — a finding that means “the glyburide story has turned out to be a little more complicated.” With metformin, there was a positive change in insulin secretion as well as insulin sensitivity.
The authors’ conclusion, she noted, “is that there’s potential in thinking about metformin first, as the primary treatment, and then adding glyburide after that.”
Future Use Of Incretin Mimetics, and Intensive Targets in Overweight/Obesity
Dr. Feghali wonders whether incretin hormone mimetics — such as glucagonlike peptide–1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) — could play a future role in GDM treatment, helping to increase insulin secretion.
She is currently recruiting for a pilot study on the pharmacokinetics and pharmacodynamics in GDM of exenatide, a FDA-approved GLP-1 agonist that has been shown not to cross the placenta and that should, research suggests, lower the risk of maternal hypoglycemia and limit the risk of excessive fetal growth, “overcoming some of the concerns we have with glyburide,” Dr. Feghali said.
A recent study of the gut-generated incretin response during an oral glucose tolerance test in pregnant women with and without GDM showed that post-load GLP-1 and GIP were higher in women with GDM, and that the GLP-1 secretion was associated with insulin secretion only in those with GDM (J Clin Endocrinol Metab. 2022;107(6):e2425-30). “In those with normal OGTT, insulin secretion was independent of GLP-1,” she said. “This study suggests there’s a potential role for incretin mimetics in GDM.”
Also regarding the individualization of GDM treatment, patients who are overweight or obese in the prepregnancy setting and have gestational diabetes represent a different phenotype, she noted, with higher fasting and postprandial blood glucose compared to normal-weight counterparts despite higher doses of medication.
“After controlling for gestational weight gain and glycemic control, we see there’s an independent effect of prepregnancy obesity specifically for an increased risk of macrosomia, preterm birth, and hypertensive disorders of pregnancy,” said Dr. Feghali, referring to a 2015 retrospective study of GDM and obesity (Obstet Gynecol. 2015;126:316-25). “It suggests that we might think about redrawing the line, not on diagnosis and screening but on treatment.”
The randomized, controlled Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus (iGDM) trial, is now recruiting at multiple centers, including at Dr. Feghali’s University of Pittsburgh, and will investigate the effect of intensive glycemic targets (fasting < 90 mg/dL, 1-hour postprandial < 120 mg/dL) versus standard glycemic targets (fasting < 95 mg/dL, 1-hour postprandial < 140 mg/dL), she said.
In another presentation on GDM, Monica Longo, MD, PhD, of the Inova Health System in Fairfax, Va., said researchers are also looking at whether nutritional supplements such as myo-inositol can reduce the risk of adverse pregnancy outcomes in GDM, and whether probiotics can improve insulin sensitivity in some patients.
Data on newer insulin analogs in pregnancy are lacking, she noted. “Preliminary data has shown no malformations in infants, but there is some increase in hypoglycemia-related admissions to the NICU,” she said. “It’s worth it [to research more].”
FAIRFAX, VIRGINIA — , but researchers at the biennial meeting of the Diabetes in Pregnancy Study Group of North America expressed hope for more clarity in the near future and the ability to someday individualize treatment to account for what is increasingly viewed as a heterogeneous condition.
Until studies in 2015 and 2018 cast doubt on glyburide, “we used to have 80% [of our GDM patients] on glyburide, and 20% on insulin,” Maisa Feghali, MD, of the University of Pittsburgh, said during a discussion period. “Now we have 95% on insulin and 5% on oral hypoglycemics. I rely on insulin because I don’t have a better option, and I rely on research efforts [underway to provide better options]” in the future.
The American College of Obstetricians and Gynecologists recommends insulin as the preferred first-line pharmacologic therapy for GDM when pharmacologic therapy is needed, with metformin as an option when patients decline or cannot safely use insulin. Glyburide, ACOG said in its 2018 practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64), should not be recommended as a first-line pharmacologic therapy.
The Society of Maternal-Fetal Medicine, on the other hand, has accepted metformin as a “reasonable and safe” first-line alternative to insulin — while recognizing that half of women will still require insulin to achieve glycemic control — and does not rule out consideration of glyburide. In its 2018 statement on the pharmacologic treatment of GDM, the society said that the evidence of benefit of one oral agent over another remains limited.
“When you have dueling guidelines, it means the data are not that clear,” George Saade, MD, professor and chair of obstetrics and gynecology at the Eastern Virginia School of Medicine, Norfolk, said in a presentation on GDM. An upcoming $12 million multicenter study to be led by the Ohio State University College of Medicine — coined the DECIDE trial — should provide clarity, he said.
The trial, funded by the Patient-Centered Outcomes Research Institute, which funds comparative clinical effectiveness research designed to be broadly applicable to practice, will enroll and randomize over 1500 pregnant individuals with GDM to either oral metformin or insulin and will follow mothers and children until 2 years after delivery.
The study’s primary and secondary hypotheses, respectively, are that metformin is not inferior to insulin in reducing a composite adverse neonatal outcome (large for gestational age, neonatal hypoglycemia and/or hyperbilirubemia) and that metformin does not result in increased child body mass index at 2 years, compared with insulin. It will also look at patient-reported factors associated with metformin use compared to insulin use — factors that “are important ... to enable clinical implementation of study findings,” said Dr. Saade, who played a role in designing the study over the past several years.
The study will take a pragmatic, real-world approach by ensuring racial and ethnic, socioeconomic, urban and rural, and geographic diversity at both large academic and community-based sites across the United States.
The trial, to be led by Mark Landon, MD, and Kartik Venkatesh, MD, PhD, of Ohio State University, will be the first large trial in the United States to both directly compare the ability of oral hypoglycemics and insulin to prevent GDM-associated pregnancy complications, and to follow children for 2 years, Dr. Saade said. “Prior research was either outside the United States, not randomized, not adequately powered, or had no long-term child follow-up,” he added after the meeting.
The State Of Knowledge About Oral Hypoglycemics
The trial was envisioned several years ago as a three-arm comparative trial including the sulfonylurea glyburide, but data published in recent years has increasingly “not favored” glyburide, and many providers “have stopped using it,” Dr. Saade said during and after the meeting. At this point, “it would not be useful to include it” in a pragmatic trial, he said.
Glyburide became the number one agent after a seminal trial published in 2000 (N Engl J Med. 2000;343:1134-8) showed equivalent glycemic control in about 400 women with GDM who were randomized to receive insulin or glyburide. While the trial was not powered to evaluate other outcomes, there were no significant differences in neonatal complications.
In 2015, a large retrospective population-based study (JAMA Pediatr. 2015;169[5]:452-8) of more than 9,000 women with GDM showed higher risks of neonatal intensive care admission, neonatal hypoglycemia, and large-for-gestational age with glyburide compared with insulin. “It prompted a pause in thinking,” Dr. Saade recalled at the DPSG meeting. After that, several meta-analyses/systematic reviews compared the two treatments, showing varying and sometimes conflicting degrees of difference in neonatal outcomes.
In 2018, a French noninferiority randomized controlled trial (JAMA 2018;319[17]:1773-80) did not show that glyburide is not inferior to insulin in the prevention of perinatal outcomes (macrosomia, neonatal hypoglycemia, and hyperbilirubinemia). “If you add this trial to the systematic reviews, it would probably would shift more in favor of insulin,” Dr. Saade said, noting that the trial’s supplementary data included a higher rate of maternal hypoglycemia with glyburide. “I feel personally now, with all the data, that glyburide is inferior to insulin.”
A 2021 network meta-analysis (BMC Endocr Disord. 2021;21:199) that looked at glycemic control and neonatal outcomes in GDM treated with glyburide, metformin, or insulin, also offers valuable insight, Dr. Saade said. The meta-analysis used a Bayesian framework and presents results as a ranking estimated probability of a treatment being the best or worst — or in between — for different outcomes (glycemic control and neonatal outcomes), which “is one of the best ways to look at data these days,” he said.
“It tells us how likely [it is for one agent] to be better than others. Will it work most of the time? More than 60% of the time?” Dr. Saade explained. For example, the analysis “tell us that for large for gestational age, glyburide has a 94% chance of being the worst, metformin has an 80% change of being the best, and insulin a 76% chance of being in between.”
Overall, the 2021 analysis suggests that “glyburide is the most likely to be worst in most outcomes and that there is equipoise between metformin and insulin,” he said.
Meta-analyses of pharmacologic treatment of GDM have been challenged, he said, by inconsistent reporting in trials of GDM diagnostic criteria, severity of hyperglycemia, and small sample sizes (and wide confidence intervals). Criteria for supplemental insulin are also often “unclear” in trials, Dr. Saade said, as is involvement of social determinants of health and the “care package” enveloping pharmacologic interventions.
Dr. Saade, Dr. Landon, and other researchers have also lamented over the years that there is limited long-term follow-up of exposed offspring.
The Challenge of Heterogeneity
In another presentation on GDM, Maisa Feghali, MD, MS, emphasized that GDM is a heterogeneous condition, with clinical hyperglycemia not capturing individual variation in underlying physiologic processes. A 2016 study (Diabetes Care. 2016;39[6]:1052-5) assessing insulin sensitivity and secretion in 800-plus women at 24-30 weeks’ gestation found that about 50% of those with GDM had predominant insulin resistance, 30% had predominant insulin secretion deficit, and 20% were mixed.
Those with predominant insulin resistance had higher BMI, higher fasting glucose, larger infants, and greater risk of GDM-associated adverse outcomes, “suggesting that the risk is not universal or equivalent,” said Dr. Feghali, assistant professor in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh and the UPCM Magee-Women’s Hospital.
A 2019 multicenter European study (Diabetologia. 2019;62[11]:2118-28) found an even higher proportion of GDM involving predominant insulin resistance and, similarly, a greater risk of adverse pregnancy outcomes in these women than in insulin-sensitive women with GDM, “again suggesting that there’s probably some benefit to looking deeper at physiology to understand individual risk,” she said.
Research published decades ago showed that insulin sensitivity decreases by over 50% during pregnancy, and “what we’ve come to recognize is there [can be] insulin secretion deficiency that’s not able to surmount or overcome the insulin resistance that develops during advanced gestation,” she said. “We need to think not at the population level but at the individual level.”
Dr. Feghali is leading the MATCh-GDM (Metabolic Analysis for Treatment Choice in GDM) study, which has been randomizing women to receive either usual, unmatched treatment or treatment matched to GDM mechanism — metformin for predominant insulin resistance, glyburide, or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. Data are not available yet.
There is still more to be learned about the pharmacologic effects of oral hypoglycemics, she noted, pointing to a 2020 study (Clin Pharmacol Ther. 2020;107[6]:1362-72) that randomized women to glyburide, metformin, or glyburide/metformin combination therapy and measured insulin sensitivity, beta-cell responsivity, and disposition index. (The latter describes the overall metabolic state and is a product of insulin sensitivity and total beta-cell responsivity.)
“Somewhat surprisingly, they found metformin performed better than glyburide,” shifting the overall disposition index closer to normal, Dr. Feghali said. “But not surprisingly, they found the combination worked best.”
Total beta-cell responsivity occurred in 56% of the glyburide group and 74% of the combination group. Improvements in insulin sensitivity occurred in 84% of the metformin group and 74% of the combination group. Surprisingly, there was “a decrease in first-phase insulin secretion” with glyburide, noted Dr. Feghali — a finding that means “the glyburide story has turned out to be a little more complicated.” With metformin, there was a positive change in insulin secretion as well as insulin sensitivity.
The authors’ conclusion, she noted, “is that there’s potential in thinking about metformin first, as the primary treatment, and then adding glyburide after that.”
Future Use Of Incretin Mimetics, and Intensive Targets in Overweight/Obesity
Dr. Feghali wonders whether incretin hormone mimetics — such as glucagonlike peptide–1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) — could play a future role in GDM treatment, helping to increase insulin secretion.
She is currently recruiting for a pilot study on the pharmacokinetics and pharmacodynamics in GDM of exenatide, a FDA-approved GLP-1 agonist that has been shown not to cross the placenta and that should, research suggests, lower the risk of maternal hypoglycemia and limit the risk of excessive fetal growth, “overcoming some of the concerns we have with glyburide,” Dr. Feghali said.
A recent study of the gut-generated incretin response during an oral glucose tolerance test in pregnant women with and without GDM showed that post-load GLP-1 and GIP were higher in women with GDM, and that the GLP-1 secretion was associated with insulin secretion only in those with GDM (J Clin Endocrinol Metab. 2022;107(6):e2425-30). “In those with normal OGTT, insulin secretion was independent of GLP-1,” she said. “This study suggests there’s a potential role for incretin mimetics in GDM.”
Also regarding the individualization of GDM treatment, patients who are overweight or obese in the prepregnancy setting and have gestational diabetes represent a different phenotype, she noted, with higher fasting and postprandial blood glucose compared to normal-weight counterparts despite higher doses of medication.
“After controlling for gestational weight gain and glycemic control, we see there’s an independent effect of prepregnancy obesity specifically for an increased risk of macrosomia, preterm birth, and hypertensive disorders of pregnancy,” said Dr. Feghali, referring to a 2015 retrospective study of GDM and obesity (Obstet Gynecol. 2015;126:316-25). “It suggests that we might think about redrawing the line, not on diagnosis and screening but on treatment.”
The randomized, controlled Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus (iGDM) trial, is now recruiting at multiple centers, including at Dr. Feghali’s University of Pittsburgh, and will investigate the effect of intensive glycemic targets (fasting < 90 mg/dL, 1-hour postprandial < 120 mg/dL) versus standard glycemic targets (fasting < 95 mg/dL, 1-hour postprandial < 140 mg/dL), she said.
In another presentation on GDM, Monica Longo, MD, PhD, of the Inova Health System in Fairfax, Va., said researchers are also looking at whether nutritional supplements such as myo-inositol can reduce the risk of adverse pregnancy outcomes in GDM, and whether probiotics can improve insulin sensitivity in some patients.
Data on newer insulin analogs in pregnancy are lacking, she noted. “Preliminary data has shown no malformations in infants, but there is some increase in hypoglycemia-related admissions to the NICU,” she said. “It’s worth it [to research more].”
FAIRFAX, VIRGINIA — , but researchers at the biennial meeting of the Diabetes in Pregnancy Study Group of North America expressed hope for more clarity in the near future and the ability to someday individualize treatment to account for what is increasingly viewed as a heterogeneous condition.
Until studies in 2015 and 2018 cast doubt on glyburide, “we used to have 80% [of our GDM patients] on glyburide, and 20% on insulin,” Maisa Feghali, MD, of the University of Pittsburgh, said during a discussion period. “Now we have 95% on insulin and 5% on oral hypoglycemics. I rely on insulin because I don’t have a better option, and I rely on research efforts [underway to provide better options]” in the future.
The American College of Obstetricians and Gynecologists recommends insulin as the preferred first-line pharmacologic therapy for GDM when pharmacologic therapy is needed, with metformin as an option when patients decline or cannot safely use insulin. Glyburide, ACOG said in its 2018 practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64), should not be recommended as a first-line pharmacologic therapy.
The Society of Maternal-Fetal Medicine, on the other hand, has accepted metformin as a “reasonable and safe” first-line alternative to insulin — while recognizing that half of women will still require insulin to achieve glycemic control — and does not rule out consideration of glyburide. In its 2018 statement on the pharmacologic treatment of GDM, the society said that the evidence of benefit of one oral agent over another remains limited.
“When you have dueling guidelines, it means the data are not that clear,” George Saade, MD, professor and chair of obstetrics and gynecology at the Eastern Virginia School of Medicine, Norfolk, said in a presentation on GDM. An upcoming $12 million multicenter study to be led by the Ohio State University College of Medicine — coined the DECIDE trial — should provide clarity, he said.
The trial, funded by the Patient-Centered Outcomes Research Institute, which funds comparative clinical effectiveness research designed to be broadly applicable to practice, will enroll and randomize over 1500 pregnant individuals with GDM to either oral metformin or insulin and will follow mothers and children until 2 years after delivery.
The study’s primary and secondary hypotheses, respectively, are that metformin is not inferior to insulin in reducing a composite adverse neonatal outcome (large for gestational age, neonatal hypoglycemia and/or hyperbilirubemia) and that metformin does not result in increased child body mass index at 2 years, compared with insulin. It will also look at patient-reported factors associated with metformin use compared to insulin use — factors that “are important ... to enable clinical implementation of study findings,” said Dr. Saade, who played a role in designing the study over the past several years.
The study will take a pragmatic, real-world approach by ensuring racial and ethnic, socioeconomic, urban and rural, and geographic diversity at both large academic and community-based sites across the United States.
The trial, to be led by Mark Landon, MD, and Kartik Venkatesh, MD, PhD, of Ohio State University, will be the first large trial in the United States to both directly compare the ability of oral hypoglycemics and insulin to prevent GDM-associated pregnancy complications, and to follow children for 2 years, Dr. Saade said. “Prior research was either outside the United States, not randomized, not adequately powered, or had no long-term child follow-up,” he added after the meeting.
The State Of Knowledge About Oral Hypoglycemics
The trial was envisioned several years ago as a three-arm comparative trial including the sulfonylurea glyburide, but data published in recent years has increasingly “not favored” glyburide, and many providers “have stopped using it,” Dr. Saade said during and after the meeting. At this point, “it would not be useful to include it” in a pragmatic trial, he said.
Glyburide became the number one agent after a seminal trial published in 2000 (N Engl J Med. 2000;343:1134-8) showed equivalent glycemic control in about 400 women with GDM who were randomized to receive insulin or glyburide. While the trial was not powered to evaluate other outcomes, there were no significant differences in neonatal complications.
In 2015, a large retrospective population-based study (JAMA Pediatr. 2015;169[5]:452-8) of more than 9,000 women with GDM showed higher risks of neonatal intensive care admission, neonatal hypoglycemia, and large-for-gestational age with glyburide compared with insulin. “It prompted a pause in thinking,” Dr. Saade recalled at the DPSG meeting. After that, several meta-analyses/systematic reviews compared the two treatments, showing varying and sometimes conflicting degrees of difference in neonatal outcomes.
In 2018, a French noninferiority randomized controlled trial (JAMA 2018;319[17]:1773-80) did not show that glyburide is not inferior to insulin in the prevention of perinatal outcomes (macrosomia, neonatal hypoglycemia, and hyperbilirubinemia). “If you add this trial to the systematic reviews, it would probably would shift more in favor of insulin,” Dr. Saade said, noting that the trial’s supplementary data included a higher rate of maternal hypoglycemia with glyburide. “I feel personally now, with all the data, that glyburide is inferior to insulin.”
A 2021 network meta-analysis (BMC Endocr Disord. 2021;21:199) that looked at glycemic control and neonatal outcomes in GDM treated with glyburide, metformin, or insulin, also offers valuable insight, Dr. Saade said. The meta-analysis used a Bayesian framework and presents results as a ranking estimated probability of a treatment being the best or worst — or in between — for different outcomes (glycemic control and neonatal outcomes), which “is one of the best ways to look at data these days,” he said.
“It tells us how likely [it is for one agent] to be better than others. Will it work most of the time? More than 60% of the time?” Dr. Saade explained. For example, the analysis “tell us that for large for gestational age, glyburide has a 94% chance of being the worst, metformin has an 80% change of being the best, and insulin a 76% chance of being in between.”
Overall, the 2021 analysis suggests that “glyburide is the most likely to be worst in most outcomes and that there is equipoise between metformin and insulin,” he said.
Meta-analyses of pharmacologic treatment of GDM have been challenged, he said, by inconsistent reporting in trials of GDM diagnostic criteria, severity of hyperglycemia, and small sample sizes (and wide confidence intervals). Criteria for supplemental insulin are also often “unclear” in trials, Dr. Saade said, as is involvement of social determinants of health and the “care package” enveloping pharmacologic interventions.
Dr. Saade, Dr. Landon, and other researchers have also lamented over the years that there is limited long-term follow-up of exposed offspring.
The Challenge of Heterogeneity
In another presentation on GDM, Maisa Feghali, MD, MS, emphasized that GDM is a heterogeneous condition, with clinical hyperglycemia not capturing individual variation in underlying physiologic processes. A 2016 study (Diabetes Care. 2016;39[6]:1052-5) assessing insulin sensitivity and secretion in 800-plus women at 24-30 weeks’ gestation found that about 50% of those with GDM had predominant insulin resistance, 30% had predominant insulin secretion deficit, and 20% were mixed.
Those with predominant insulin resistance had higher BMI, higher fasting glucose, larger infants, and greater risk of GDM-associated adverse outcomes, “suggesting that the risk is not universal or equivalent,” said Dr. Feghali, assistant professor in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh and the UPCM Magee-Women’s Hospital.
A 2019 multicenter European study (Diabetologia. 2019;62[11]:2118-28) found an even higher proportion of GDM involving predominant insulin resistance and, similarly, a greater risk of adverse pregnancy outcomes in these women than in insulin-sensitive women with GDM, “again suggesting that there’s probably some benefit to looking deeper at physiology to understand individual risk,” she said.
Research published decades ago showed that insulin sensitivity decreases by over 50% during pregnancy, and “what we’ve come to recognize is there [can be] insulin secretion deficiency that’s not able to surmount or overcome the insulin resistance that develops during advanced gestation,” she said. “We need to think not at the population level but at the individual level.”
Dr. Feghali is leading the MATCh-GDM (Metabolic Analysis for Treatment Choice in GDM) study, which has been randomizing women to receive either usual, unmatched treatment or treatment matched to GDM mechanism — metformin for predominant insulin resistance, glyburide, or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. Data are not available yet.
There is still more to be learned about the pharmacologic effects of oral hypoglycemics, she noted, pointing to a 2020 study (Clin Pharmacol Ther. 2020;107[6]:1362-72) that randomized women to glyburide, metformin, or glyburide/metformin combination therapy and measured insulin sensitivity, beta-cell responsivity, and disposition index. (The latter describes the overall metabolic state and is a product of insulin sensitivity and total beta-cell responsivity.)
“Somewhat surprisingly, they found metformin performed better than glyburide,” shifting the overall disposition index closer to normal, Dr. Feghali said. “But not surprisingly, they found the combination worked best.”
Total beta-cell responsivity occurred in 56% of the glyburide group and 74% of the combination group. Improvements in insulin sensitivity occurred in 84% of the metformin group and 74% of the combination group. Surprisingly, there was “a decrease in first-phase insulin secretion” with glyburide, noted Dr. Feghali — a finding that means “the glyburide story has turned out to be a little more complicated.” With metformin, there was a positive change in insulin secretion as well as insulin sensitivity.
The authors’ conclusion, she noted, “is that there’s potential in thinking about metformin first, as the primary treatment, and then adding glyburide after that.”
Future Use Of Incretin Mimetics, and Intensive Targets in Overweight/Obesity
Dr. Feghali wonders whether incretin hormone mimetics — such as glucagonlike peptide–1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) — could play a future role in GDM treatment, helping to increase insulin secretion.
She is currently recruiting for a pilot study on the pharmacokinetics and pharmacodynamics in GDM of exenatide, a FDA-approved GLP-1 agonist that has been shown not to cross the placenta and that should, research suggests, lower the risk of maternal hypoglycemia and limit the risk of excessive fetal growth, “overcoming some of the concerns we have with glyburide,” Dr. Feghali said.
A recent study of the gut-generated incretin response during an oral glucose tolerance test in pregnant women with and without GDM showed that post-load GLP-1 and GIP were higher in women with GDM, and that the GLP-1 secretion was associated with insulin secretion only in those with GDM (J Clin Endocrinol Metab. 2022;107(6):e2425-30). “In those with normal OGTT, insulin secretion was independent of GLP-1,” she said. “This study suggests there’s a potential role for incretin mimetics in GDM.”
Also regarding the individualization of GDM treatment, patients who are overweight or obese in the prepregnancy setting and have gestational diabetes represent a different phenotype, she noted, with higher fasting and postprandial blood glucose compared to normal-weight counterparts despite higher doses of medication.
“After controlling for gestational weight gain and glycemic control, we see there’s an independent effect of prepregnancy obesity specifically for an increased risk of macrosomia, preterm birth, and hypertensive disorders of pregnancy,” said Dr. Feghali, referring to a 2015 retrospective study of GDM and obesity (Obstet Gynecol. 2015;126:316-25). “It suggests that we might think about redrawing the line, not on diagnosis and screening but on treatment.”
The randomized, controlled Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus (iGDM) trial, is now recruiting at multiple centers, including at Dr. Feghali’s University of Pittsburgh, and will investigate the effect of intensive glycemic targets (fasting < 90 mg/dL, 1-hour postprandial < 120 mg/dL) versus standard glycemic targets (fasting < 95 mg/dL, 1-hour postprandial < 140 mg/dL), she said.
In another presentation on GDM, Monica Longo, MD, PhD, of the Inova Health System in Fairfax, Va., said researchers are also looking at whether nutritional supplements such as myo-inositol can reduce the risk of adverse pregnancy outcomes in GDM, and whether probiotics can improve insulin sensitivity in some patients.
Data on newer insulin analogs in pregnancy are lacking, she noted. “Preliminary data has shown no malformations in infants, but there is some increase in hypoglycemia-related admissions to the NICU,” she said. “It’s worth it [to research more].”
FROM DPSG-NA 2023
The Knowns and Unknowns About Delivery Timing in Diabetes
FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.
“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.
The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.
“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
ACOG Recommendations, Randomized Trials (New And Old)
The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).
In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.
ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.
The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.
The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)
Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).
Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.
What Retrospective Studies Reveal
Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.
Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”
The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.
However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).
In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)
The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.
Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.
In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).
Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”
Dr. Grantz reported no disclosures.
FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.
“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.
The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.
“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
ACOG Recommendations, Randomized Trials (New And Old)
The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).
In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.
ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.
The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.
The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)
Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).
Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.
What Retrospective Studies Reveal
Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.
Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”
The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.
However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).
In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)
The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.
Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.
In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).
Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”
Dr. Grantz reported no disclosures.
FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.
“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.
The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.
“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
ACOG Recommendations, Randomized Trials (New And Old)
The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).
In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.
ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.
The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.
The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)
Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).
Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.
What Retrospective Studies Reveal
Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.
Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”
The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.
However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).
In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)
The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.
Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.
In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).
Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”
Dr. Grantz reported no disclosures.
FROM DPSG-NA 2023
Myo-inositol is one of the components of an integrative approach to acne
, Jonette Elizabeth Keri, MD, PhD, professor of dermatology at the University of Miami, said during a presentation on therapies for acne at the annual Integrative Dermatology Symposium.
Probiotics and omega-3 fatty acids are among the other complementary therapies that have a role in acne treatment, she and others said during the meeting.
Myo-inositol has been well-studied in the gynecology-endocrinology community in patients with polycystic ovary syndrome (PCOS), demonstrating an ability to improve the metabolic profile and reduce acne and hirsutism, Dr. Keri said.
A study of 137 young, overweight women with PCOS and moderate acne, for example, found that compared with placebo, 6 months of myo-inositol or D-chiro-inositol, another isoform of inositol, significantly improved the acne score, endocrine and metabolic parameters, insulin resistance, and regularity of the menstrual cycle, Dr. Keri said. Both isoforms of inositol are second messengers in the signal transduction of insulin.
During a panel discussion, asked about a case of an adult female with acne, Dr. Keri said that many of her adult female patients “don’t want to do isotretinoin or antibiotics, and they don’t want to do any kind of hormonal treatment,” the options she would recommend. But for patients who do not want these treatments, she said, “I go down the route of supplements,” and myo-inositol is her “favorite” option. It’s safe to use during pregnancy, she emphasized, noting that myo-inositol is being studied for the prevention of preterm birth.
Dr. Keri, who described herself as “more of a traditionalist,” prescribes myo-inositol 2 gm twice a day in pill form. In Europe, she noted in her presentation, myo-inositol is also compounded for topical use.
Diet, probiotics, other nutraceuticals
A low-glycemic-load diet was among several complementary therapies reported in a 2015 Cochrane Database Systematic Review to have some evidence (though low-quality) of reducing total skin lesions in acne (along with tea tree oil and bee venom) and today, it is the most evidence-based dietary recommendation for acne, Dr. Keri said.
Omega-3 fatty acids and increased fruit and vegetable intake have also been reported to be acne-protective — and hyperglycemia, carbohydrates, milk and dairy products, and saturated fats and trans fats have been reported to be acne-promoting, she noted.
But, the low-glycemic-load data “is the strongest,” she said. The best advice for patients, she added, is to consume less sugar and fewer sugary drinks and “avoid white foods” such as white bread, rice, and pasta.
Probiotics can also be recommended, especially for patients on antibiotic therapy, Dr. Keri said. For “basic science evidence,” she pointed to a randomized, double-blinded, placebo-controlled study of 20 adults with acne, which evaluated the impact of a probiotic on improvement in acne and skin expression of genes involved with insulin signaling. Participants took either a liquid supplement containing Lactobacillus rhamnosus SP1 (LSP1) or placebo over a 12-week period. The investigators performed paired skin biopsies before and after 12 weeks of treatment and analyzed them for insulin-like growth factor 1 (IGF1) and forkhead box protein O1 (FOXO1) gene expression.
They found that compared with baseline, the probiotic group showed a 32% reduction in IGF1 and a 65% increase in FOXO1 gene expression (P < .0001 for both), with no such differences observed in the placebo group.
Clinically, patients in the probiotic group had an adjusted odds ratio of 28.4 (95% confidence interval, 2.2-411.1, P < .05) of acne being rated as improved or markedly improved compared with those on placebo.
Dr. Keri and others at the meeting also referenced a 2013 prospective, open-label trial that randomized 45 women with acne, ages 18-35 years, to one of three arms: Probiotic supplementation only, minocycline only, and both probiotic and minocycline. The probiotic used was a product containing Lactobacillus acidophilus, Lactobacillus bulgaricus, and Bifidobacterium bifidum. At 8 and 12 weeks, the combination group “did the best with the lowest total lesion count” compared with the probiotic group and the minocycline group, differences that were significant (P < .001 and P <.01, respectively), she said. “And they also had less candidiasis when using a probiotic than when using an antibiotic alone,” she said. Two patients in the minocycline-only group failed to complete the study because they developed vaginal candidiasis.
In addition to reducing potential adverse events secondary to chronic antibiotic use, probiotics can have synergistic anti-inflammatory effects, she said.
Dr. Keri said she recommends probiotics for patients taking antibiotics and encourages them “to get a branded probiotic,” such as Culturelle, “or if they prefer a food source, soy or almond milk–based yogurt.” As with other elements of a holistic approach to acne, she urged clinicians to consider the cost of treatment.
Probiotics (Lactobacillus plantarum) were one of four nutraceuticals determined in a 2023 systematic review to have “good-quality” evidence for potential efficacy, Dr. Keri noted, along with vitamin D, green tea extract, and cheongsangbangpoong-tang, the latter of which is an herbal therapeutic formula approved by the Korean Food and Drug Administration for use in acne.
“There were really no bad systemic effects for any of these,” she said. “The tricky part of this review is that each of the four have only one study” deemed to be a good-quality study. Omega-3 fatty acids were among several other nutraceuticals deemed to have “fair-quality” evidence for efficacy. Zinc was reported to be the most studied nutraceutical in acne, but didn’t rate as highly in the review. Dr. Keri said she likes to include zinc in her armamentarium because “it can be used in pregnant women,” noting that reviews and guidelines “are just that, a guide ... to combine with experience.”
Omega-3 fatty acids with isotretinoin
Several speakers at the meeting, including Steven Daveluy, MD, associate professor and residency program director in the department of dermatology, Wayne State University, Dearborn, Michigan, spoke about the value of omega-3 fatty acids in reducing side effects of isotretinoin. “In the FDA trials [of isotretinoin] they had patients take 50 grams of fat,” he said. “You can use the good fats to help you out.”
Research has shown that 1 gm per day of oral omega-3 reduces dryness of the lips, nose, eyes, and skin, “which are the big side effects we see with isotretinoin,” he said. An impact on triglyceride levels has also been demonstrated, Dr. Daveluy said, pointing to a longitudinal survey study of 39 patients treated with isotretinoin that showed a mean increase in triglyceride levels of 49% during treatment in patients who did not use omega-3 supplementation, compared with a mean increase of 13.9% (P =.04) in patients who used the supplements.“There is also evidence that omega-3 can decrease depression, which may or may not be a side effect of isotretinoin ... but it’s something we consider in our [acne] patients,” Dr. Daveluy said.
During a panel discussion at the meeting, Apple A. Bodemer, MD, associate professor of dermatology at the University of Wisconsin, Madison, said she usually prescribes 2 g of docosahexaenoic acid eicosapentaenoic acid combined in patients on isotretinoin because “at that dose, omega-3s have been found to be anti-inflammatory.”
Dr. Keri reported being an investigator and speaker for Galderma, and an advisory board member for Ortho Dermatologics and for Almirall. Dr. Daveluy reported no relevant disclosures.
, Jonette Elizabeth Keri, MD, PhD, professor of dermatology at the University of Miami, said during a presentation on therapies for acne at the annual Integrative Dermatology Symposium.
Probiotics and omega-3 fatty acids are among the other complementary therapies that have a role in acne treatment, she and others said during the meeting.
Myo-inositol has been well-studied in the gynecology-endocrinology community in patients with polycystic ovary syndrome (PCOS), demonstrating an ability to improve the metabolic profile and reduce acne and hirsutism, Dr. Keri said.
A study of 137 young, overweight women with PCOS and moderate acne, for example, found that compared with placebo, 6 months of myo-inositol or D-chiro-inositol, another isoform of inositol, significantly improved the acne score, endocrine and metabolic parameters, insulin resistance, and regularity of the menstrual cycle, Dr. Keri said. Both isoforms of inositol are second messengers in the signal transduction of insulin.
During a panel discussion, asked about a case of an adult female with acne, Dr. Keri said that many of her adult female patients “don’t want to do isotretinoin or antibiotics, and they don’t want to do any kind of hormonal treatment,” the options she would recommend. But for patients who do not want these treatments, she said, “I go down the route of supplements,” and myo-inositol is her “favorite” option. It’s safe to use during pregnancy, she emphasized, noting that myo-inositol is being studied for the prevention of preterm birth.
Dr. Keri, who described herself as “more of a traditionalist,” prescribes myo-inositol 2 gm twice a day in pill form. In Europe, she noted in her presentation, myo-inositol is also compounded for topical use.
Diet, probiotics, other nutraceuticals
A low-glycemic-load diet was among several complementary therapies reported in a 2015 Cochrane Database Systematic Review to have some evidence (though low-quality) of reducing total skin lesions in acne (along with tea tree oil and bee venom) and today, it is the most evidence-based dietary recommendation for acne, Dr. Keri said.
Omega-3 fatty acids and increased fruit and vegetable intake have also been reported to be acne-protective — and hyperglycemia, carbohydrates, milk and dairy products, and saturated fats and trans fats have been reported to be acne-promoting, she noted.
But, the low-glycemic-load data “is the strongest,” she said. The best advice for patients, she added, is to consume less sugar and fewer sugary drinks and “avoid white foods” such as white bread, rice, and pasta.
Probiotics can also be recommended, especially for patients on antibiotic therapy, Dr. Keri said. For “basic science evidence,” she pointed to a randomized, double-blinded, placebo-controlled study of 20 adults with acne, which evaluated the impact of a probiotic on improvement in acne and skin expression of genes involved with insulin signaling. Participants took either a liquid supplement containing Lactobacillus rhamnosus SP1 (LSP1) or placebo over a 12-week period. The investigators performed paired skin biopsies before and after 12 weeks of treatment and analyzed them for insulin-like growth factor 1 (IGF1) and forkhead box protein O1 (FOXO1) gene expression.
They found that compared with baseline, the probiotic group showed a 32% reduction in IGF1 and a 65% increase in FOXO1 gene expression (P < .0001 for both), with no such differences observed in the placebo group.
Clinically, patients in the probiotic group had an adjusted odds ratio of 28.4 (95% confidence interval, 2.2-411.1, P < .05) of acne being rated as improved or markedly improved compared with those on placebo.
Dr. Keri and others at the meeting also referenced a 2013 prospective, open-label trial that randomized 45 women with acne, ages 18-35 years, to one of three arms: Probiotic supplementation only, minocycline only, and both probiotic and minocycline. The probiotic used was a product containing Lactobacillus acidophilus, Lactobacillus bulgaricus, and Bifidobacterium bifidum. At 8 and 12 weeks, the combination group “did the best with the lowest total lesion count” compared with the probiotic group and the minocycline group, differences that were significant (P < .001 and P <.01, respectively), she said. “And they also had less candidiasis when using a probiotic than when using an antibiotic alone,” she said. Two patients in the minocycline-only group failed to complete the study because they developed vaginal candidiasis.
In addition to reducing potential adverse events secondary to chronic antibiotic use, probiotics can have synergistic anti-inflammatory effects, she said.
Dr. Keri said she recommends probiotics for patients taking antibiotics and encourages them “to get a branded probiotic,” such as Culturelle, “or if they prefer a food source, soy or almond milk–based yogurt.” As with other elements of a holistic approach to acne, she urged clinicians to consider the cost of treatment.
Probiotics (Lactobacillus plantarum) were one of four nutraceuticals determined in a 2023 systematic review to have “good-quality” evidence for potential efficacy, Dr. Keri noted, along with vitamin D, green tea extract, and cheongsangbangpoong-tang, the latter of which is an herbal therapeutic formula approved by the Korean Food and Drug Administration for use in acne.
“There were really no bad systemic effects for any of these,” she said. “The tricky part of this review is that each of the four have only one study” deemed to be a good-quality study. Omega-3 fatty acids were among several other nutraceuticals deemed to have “fair-quality” evidence for efficacy. Zinc was reported to be the most studied nutraceutical in acne, but didn’t rate as highly in the review. Dr. Keri said she likes to include zinc in her armamentarium because “it can be used in pregnant women,” noting that reviews and guidelines “are just that, a guide ... to combine with experience.”
Omega-3 fatty acids with isotretinoin
Several speakers at the meeting, including Steven Daveluy, MD, associate professor and residency program director in the department of dermatology, Wayne State University, Dearborn, Michigan, spoke about the value of omega-3 fatty acids in reducing side effects of isotretinoin. “In the FDA trials [of isotretinoin] they had patients take 50 grams of fat,” he said. “You can use the good fats to help you out.”
Research has shown that 1 gm per day of oral omega-3 reduces dryness of the lips, nose, eyes, and skin, “which are the big side effects we see with isotretinoin,” he said. An impact on triglyceride levels has also been demonstrated, Dr. Daveluy said, pointing to a longitudinal survey study of 39 patients treated with isotretinoin that showed a mean increase in triglyceride levels of 49% during treatment in patients who did not use omega-3 supplementation, compared with a mean increase of 13.9% (P =.04) in patients who used the supplements.“There is also evidence that omega-3 can decrease depression, which may or may not be a side effect of isotretinoin ... but it’s something we consider in our [acne] patients,” Dr. Daveluy said.
During a panel discussion at the meeting, Apple A. Bodemer, MD, associate professor of dermatology at the University of Wisconsin, Madison, said she usually prescribes 2 g of docosahexaenoic acid eicosapentaenoic acid combined in patients on isotretinoin because “at that dose, omega-3s have been found to be anti-inflammatory.”
Dr. Keri reported being an investigator and speaker for Galderma, and an advisory board member for Ortho Dermatologics and for Almirall. Dr. Daveluy reported no relevant disclosures.
, Jonette Elizabeth Keri, MD, PhD, professor of dermatology at the University of Miami, said during a presentation on therapies for acne at the annual Integrative Dermatology Symposium.
Probiotics and omega-3 fatty acids are among the other complementary therapies that have a role in acne treatment, she and others said during the meeting.
Myo-inositol has been well-studied in the gynecology-endocrinology community in patients with polycystic ovary syndrome (PCOS), demonstrating an ability to improve the metabolic profile and reduce acne and hirsutism, Dr. Keri said.
A study of 137 young, overweight women with PCOS and moderate acne, for example, found that compared with placebo, 6 months of myo-inositol or D-chiro-inositol, another isoform of inositol, significantly improved the acne score, endocrine and metabolic parameters, insulin resistance, and regularity of the menstrual cycle, Dr. Keri said. Both isoforms of inositol are second messengers in the signal transduction of insulin.
During a panel discussion, asked about a case of an adult female with acne, Dr. Keri said that many of her adult female patients “don’t want to do isotretinoin or antibiotics, and they don’t want to do any kind of hormonal treatment,” the options she would recommend. But for patients who do not want these treatments, she said, “I go down the route of supplements,” and myo-inositol is her “favorite” option. It’s safe to use during pregnancy, she emphasized, noting that myo-inositol is being studied for the prevention of preterm birth.
Dr. Keri, who described herself as “more of a traditionalist,” prescribes myo-inositol 2 gm twice a day in pill form. In Europe, she noted in her presentation, myo-inositol is also compounded for topical use.
Diet, probiotics, other nutraceuticals
A low-glycemic-load diet was among several complementary therapies reported in a 2015 Cochrane Database Systematic Review to have some evidence (though low-quality) of reducing total skin lesions in acne (along with tea tree oil and bee venom) and today, it is the most evidence-based dietary recommendation for acne, Dr. Keri said.
Omega-3 fatty acids and increased fruit and vegetable intake have also been reported to be acne-protective — and hyperglycemia, carbohydrates, milk and dairy products, and saturated fats and trans fats have been reported to be acne-promoting, she noted.
But, the low-glycemic-load data “is the strongest,” she said. The best advice for patients, she added, is to consume less sugar and fewer sugary drinks and “avoid white foods” such as white bread, rice, and pasta.
Probiotics can also be recommended, especially for patients on antibiotic therapy, Dr. Keri said. For “basic science evidence,” she pointed to a randomized, double-blinded, placebo-controlled study of 20 adults with acne, which evaluated the impact of a probiotic on improvement in acne and skin expression of genes involved with insulin signaling. Participants took either a liquid supplement containing Lactobacillus rhamnosus SP1 (LSP1) or placebo over a 12-week period. The investigators performed paired skin biopsies before and after 12 weeks of treatment and analyzed them for insulin-like growth factor 1 (IGF1) and forkhead box protein O1 (FOXO1) gene expression.
They found that compared with baseline, the probiotic group showed a 32% reduction in IGF1 and a 65% increase in FOXO1 gene expression (P < .0001 for both), with no such differences observed in the placebo group.
Clinically, patients in the probiotic group had an adjusted odds ratio of 28.4 (95% confidence interval, 2.2-411.1, P < .05) of acne being rated as improved or markedly improved compared with those on placebo.
Dr. Keri and others at the meeting also referenced a 2013 prospective, open-label trial that randomized 45 women with acne, ages 18-35 years, to one of three arms: Probiotic supplementation only, minocycline only, and both probiotic and minocycline. The probiotic used was a product containing Lactobacillus acidophilus, Lactobacillus bulgaricus, and Bifidobacterium bifidum. At 8 and 12 weeks, the combination group “did the best with the lowest total lesion count” compared with the probiotic group and the minocycline group, differences that were significant (P < .001 and P <.01, respectively), she said. “And they also had less candidiasis when using a probiotic than when using an antibiotic alone,” she said. Two patients in the minocycline-only group failed to complete the study because they developed vaginal candidiasis.
In addition to reducing potential adverse events secondary to chronic antibiotic use, probiotics can have synergistic anti-inflammatory effects, she said.
Dr. Keri said she recommends probiotics for patients taking antibiotics and encourages them “to get a branded probiotic,” such as Culturelle, “or if they prefer a food source, soy or almond milk–based yogurt.” As with other elements of a holistic approach to acne, she urged clinicians to consider the cost of treatment.
Probiotics (Lactobacillus plantarum) were one of four nutraceuticals determined in a 2023 systematic review to have “good-quality” evidence for potential efficacy, Dr. Keri noted, along with vitamin D, green tea extract, and cheongsangbangpoong-tang, the latter of which is an herbal therapeutic formula approved by the Korean Food and Drug Administration for use in acne.
“There were really no bad systemic effects for any of these,” she said. “The tricky part of this review is that each of the four have only one study” deemed to be a good-quality study. Omega-3 fatty acids were among several other nutraceuticals deemed to have “fair-quality” evidence for efficacy. Zinc was reported to be the most studied nutraceutical in acne, but didn’t rate as highly in the review. Dr. Keri said she likes to include zinc in her armamentarium because “it can be used in pregnant women,” noting that reviews and guidelines “are just that, a guide ... to combine with experience.”
Omega-3 fatty acids with isotretinoin
Several speakers at the meeting, including Steven Daveluy, MD, associate professor and residency program director in the department of dermatology, Wayne State University, Dearborn, Michigan, spoke about the value of omega-3 fatty acids in reducing side effects of isotretinoin. “In the FDA trials [of isotretinoin] they had patients take 50 grams of fat,” he said. “You can use the good fats to help you out.”
Research has shown that 1 gm per day of oral omega-3 reduces dryness of the lips, nose, eyes, and skin, “which are the big side effects we see with isotretinoin,” he said. An impact on triglyceride levels has also been demonstrated, Dr. Daveluy said, pointing to a longitudinal survey study of 39 patients treated with isotretinoin that showed a mean increase in triglyceride levels of 49% during treatment in patients who did not use omega-3 supplementation, compared with a mean increase of 13.9% (P =.04) in patients who used the supplements.“There is also evidence that omega-3 can decrease depression, which may or may not be a side effect of isotretinoin ... but it’s something we consider in our [acne] patients,” Dr. Daveluy said.
During a panel discussion at the meeting, Apple A. Bodemer, MD, associate professor of dermatology at the University of Wisconsin, Madison, said she usually prescribes 2 g of docosahexaenoic acid eicosapentaenoic acid combined in patients on isotretinoin because “at that dose, omega-3s have been found to be anti-inflammatory.”
Dr. Keri reported being an investigator and speaker for Galderma, and an advisory board member for Ortho Dermatologics and for Almirall. Dr. Daveluy reported no relevant disclosures.
FROM IDS 2023