Conference Coverage

Sex should be removed as a legal designation on the public part of birth certificates, the American Medical Association said June 15.

Requiring the designation can lead to discrimination and unnecessary burden on individuals whose current gender identity does not align with their designation at birth when they register for school or sports, adopt, get married, or request personal records.

A person’s sex designation at birth would still be submitted to the U.S. Standard Certificate of Live Birth for medical, public health, and statistical use only, report authors note.

Willie Underwood III, MD, MSc, author of Board Report 15, explained in reference committee testimony that a standard certificate of live birth is critical for uniformly collecting and processing data, but birth certificates are issued by the government to individuals.
 

Ten states allow gender-neutral designation

According to the report, 48 states (Tennessee and Ohio are the exceptions) and the District of Columbia allow people to amend their sex designation on their birth certificate to reflect their gender identities, but only 10 states allow for a gender-neutral designation, usually “X,” on birth certificates. The U.S. Department of State does not currently offer an option for a gender-neutral designation on U.S. passports.

“Assigning sex using binary variables in the public portion of the birth certificate fails to recognize the medical spectrum of gender identity,” Dr. Underwood said, and it can be used to discriminate.

Jeremy Toler, MD, a delegate from GLMA: Health Professionals Advancing LGBTQ Equality, testified that there is precedent for information to be removed from the public portion of the birth certificates. And much data is collected for each live birth that doesn’t show up on individuals’ birth certificates, he noted.

Dr. Toler said transgender, gender nonbinary, and individuals with differences in sex development can be placed at a disadvantage by the sex label on the birth certificate.

“We unfortunately still live in a world where it is unsafe in many cases for one’s gender to vary from the sex assigned at birth,” Dr. Toler said.

Not having this data on the widely used form will reduce unnecessary reliance on sex as a stand-in for gender, he said, and would “serve as an equalizer” since policies differ by state.

Robert Jackson, MD, an alternate delegate from the American Academy of Cosmetic Surgery, spoke against the measure.

“We as physicians need to report things accurately,” Dr. Jackson said. “All through medical school, residency, and specialty training we were supposed to delegate all of the physical findings of the patient we’re taking care of. I think when the child is born, they do have physical characteristics either male or female, and I think that probably should be on the public record. That’s just my personal opinion.”

Sarah Mae Smith, MD, delegate from California, speaking on behalf of the Women Physicians Section, said removing the sex designation is important for moving toward gender equity.

“We need to recognize [that] gender is not a binary but a spectrum,” she said. “Obligating our patients to jump through numerous administrative hoops to identify as who they are based on a sex assigned at birth primarily on genitalia is not only unnecessary but actively deleterious to their health.”
 

Race was once public on birth certificates

She noted that the report mentions that previously, information on the race of a person’s parents was included on the public portion of the birth certificate and that information was recognized to facilitate discrimination.

“Thankfully, a change was made to obviate at least that avenue for discriminatory practices,” she said. “Now, likewise, the information on sex assigned at birth is being used to undermine the rights of our transgender, intersex, and nonbinary patients.”

Arlene Seid, MD, MPH, an alternate delegate from the American Association of Public Health Physicians, said the resolution protects the aggregate data “without the discrimination associated with the individual data.”

Sex no longer has a role to play in the jobs people do, she noted, and the designation shouldn’t have to be evaluated for something like a job interview.

“Our society doesn’t need it on an individual basis for most of what occurs in public life,” Dr. Seid said.

Dr. Underwood, Dr. Toler, Dr. Jackson, Dr. Smith, and Dr. Seid declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Sex should be removed as a legal designation on the public part of birth certificates, the American Medical Association said June 15.

Requiring the designation can lead to discrimination and unnecessary burden on individuals whose current gender identity does not align with their designation at birth when they register for school or sports, adopt, get married, or request personal records.

A person’s sex designation at birth would still be submitted to the U.S. Standard Certificate of Live Birth for medical, public health, and statistical use only, report authors note.

Willie Underwood III, MD, MSc, author of Board Report 15, explained in reference committee testimony that a standard certificate of live birth is critical for uniformly collecting and processing data, but birth certificates are issued by the government to individuals.
 

Ten states allow gender-neutral designation

According to the report, 48 states (Tennessee and Ohio are the exceptions) and the District of Columbia allow people to amend their sex designation on their birth certificate to reflect their gender identities, but only 10 states allow for a gender-neutral designation, usually “X,” on birth certificates. The U.S. Department of State does not currently offer an option for a gender-neutral designation on U.S. passports.

“Assigning sex using binary variables in the public portion of the birth certificate fails to recognize the medical spectrum of gender identity,” Dr. Underwood said, and it can be used to discriminate.

Jeremy Toler, MD, a delegate from GLMA: Health Professionals Advancing LGBTQ Equality, testified that there is precedent for information to be removed from the public portion of the birth certificates. And much data is collected for each live birth that doesn’t show up on individuals’ birth certificates, he noted.

Dr. Toler said transgender, gender nonbinary, and individuals with differences in sex development can be placed at a disadvantage by the sex label on the birth certificate.

“We unfortunately still live in a world where it is unsafe in many cases for one’s gender to vary from the sex assigned at birth,” Dr. Toler said.

Not having this data on the widely used form will reduce unnecessary reliance on sex as a stand-in for gender, he said, and would “serve as an equalizer” since policies differ by state.

Robert Jackson, MD, an alternate delegate from the American Academy of Cosmetic Surgery, spoke against the measure.

“We as physicians need to report things accurately,” Dr. Jackson said. “All through medical school, residency, and specialty training we were supposed to delegate all of the physical findings of the patient we’re taking care of. I think when the child is born, they do have physical characteristics either male or female, and I think that probably should be on the public record. That’s just my personal opinion.”

Sarah Mae Smith, MD, delegate from California, speaking on behalf of the Women Physicians Section, said removing the sex designation is important for moving toward gender equity.

“We need to recognize [that] gender is not a binary but a spectrum,” she said. “Obligating our patients to jump through numerous administrative hoops to identify as who they are based on a sex assigned at birth primarily on genitalia is not only unnecessary but actively deleterious to their health.”
 

Race was once public on birth certificates

She noted that the report mentions that previously, information on the race of a person’s parents was included on the public portion of the birth certificate and that information was recognized to facilitate discrimination.

“Thankfully, a change was made to obviate at least that avenue for discriminatory practices,” she said. “Now, likewise, the information on sex assigned at birth is being used to undermine the rights of our transgender, intersex, and nonbinary patients.”

Arlene Seid, MD, MPH, an alternate delegate from the American Association of Public Health Physicians, said the resolution protects the aggregate data “without the discrimination associated with the individual data.”

Sex no longer has a role to play in the jobs people do, she noted, and the designation shouldn’t have to be evaluated for something like a job interview.

“Our society doesn’t need it on an individual basis for most of what occurs in public life,” Dr. Seid said.

Dr. Underwood, Dr. Toler, Dr. Jackson, Dr. Smith, and Dr. Seid declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Sex should be removed as a legal designation on the public part of birth certificates, the American Medical Association said June 15.

Requiring the designation can lead to discrimination and unnecessary burden on individuals whose current gender identity does not align with their designation at birth when they register for school or sports, adopt, get married, or request personal records.

A person’s sex designation at birth would still be submitted to the U.S. Standard Certificate of Live Birth for medical, public health, and statistical use only, report authors note.

Willie Underwood III, MD, MSc, author of Board Report 15, explained in reference committee testimony that a standard certificate of live birth is critical for uniformly collecting and processing data, but birth certificates are issued by the government to individuals.
 

Ten states allow gender-neutral designation

According to the report, 48 states (Tennessee and Ohio are the exceptions) and the District of Columbia allow people to amend their sex designation on their birth certificate to reflect their gender identities, but only 10 states allow for a gender-neutral designation, usually “X,” on birth certificates. The U.S. Department of State does not currently offer an option for a gender-neutral designation on U.S. passports.

“Assigning sex using binary variables in the public portion of the birth certificate fails to recognize the medical spectrum of gender identity,” Dr. Underwood said, and it can be used to discriminate.

Jeremy Toler, MD, a delegate from GLMA: Health Professionals Advancing LGBTQ Equality, testified that there is precedent for information to be removed from the public portion of the birth certificates. And much data is collected for each live birth that doesn’t show up on individuals’ birth certificates, he noted.

Dr. Toler said transgender, gender nonbinary, and individuals with differences in sex development can be placed at a disadvantage by the sex label on the birth certificate.

“We unfortunately still live in a world where it is unsafe in many cases for one’s gender to vary from the sex assigned at birth,” Dr. Toler said.

Not having this data on the widely used form will reduce unnecessary reliance on sex as a stand-in for gender, he said, and would “serve as an equalizer” since policies differ by state.

Robert Jackson, MD, an alternate delegate from the American Academy of Cosmetic Surgery, spoke against the measure.

“We as physicians need to report things accurately,” Dr. Jackson said. “All through medical school, residency, and specialty training we were supposed to delegate all of the physical findings of the patient we’re taking care of. I think when the child is born, they do have physical characteristics either male or female, and I think that probably should be on the public record. That’s just my personal opinion.”

Sarah Mae Smith, MD, delegate from California, speaking on behalf of the Women Physicians Section, said removing the sex designation is important for moving toward gender equity.

“We need to recognize [that] gender is not a binary but a spectrum,” she said. “Obligating our patients to jump through numerous administrative hoops to identify as who they are based on a sex assigned at birth primarily on genitalia is not only unnecessary but actively deleterious to their health.”
 

Race was once public on birth certificates

She noted that the report mentions that previously, information on the race of a person’s parents was included on the public portion of the birth certificate and that information was recognized to facilitate discrimination.

“Thankfully, a change was made to obviate at least that avenue for discriminatory practices,” she said. “Now, likewise, the information on sex assigned at birth is being used to undermine the rights of our transgender, intersex, and nonbinary patients.”

Arlene Seid, MD, MPH, an alternate delegate from the American Association of Public Health Physicians, said the resolution protects the aggregate data “without the discrimination associated with the individual data.”

Sex no longer has a role to play in the jobs people do, she noted, and the designation shouldn’t have to be evaluated for something like a job interview.

“Our society doesn’t need it on an individual basis for most of what occurs in public life,” Dr. Seid said.

Dr. Underwood, Dr. Toler, Dr. Jackson, Dr. Smith, and Dr. Seid declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Advances in photobiomodulation have propelled the use of therapeutic applications in a variety of medical specialties, according to Juanita J. Anders, PhD.

During the annual conference of the American Society for Laser Medicine and Surgery, Dr. Anders, professor of anatomy, physiology, and genetics at the Uniformed Services University of the Health Sciences, Bethesda, Md., defined photobiomodulation (PBM) as the mechanism by which nonionizing optical radiation in the visible and near-infrared spectral range is absorbed by endogenous chromophores to elicit photophysical and photochemical events at various biological scales. Photobiomodulation therapy (PBMT) involves the use of light sources including lasers, LEDs, and broadband light, that emit visible and/or near-infrared light to cause physiological changes in cells and tissues and result in therapeutic benefits.

In dermatology, LED light therapy devices are commonly used for PBMT in wavelengths that range from blue (415 nm) and red (633 nm) to near infrared (830 nm). “Often, when PBMT is referred to by dermatologists it’s called LED therapy or LED light therapy,” Dr. Anders noted. “Some people are under the impression that this is different from PBMT. But remember: It’s not the device that’s producing the photons that is clinically relevant, but it’s the photons themselves. In both cases, the same radiances and fluence ranges are being used and the mechanisms are the same, so it’s all PBMT.”

The therapy is used to treat a wide variety of medical and aesthetic disorders including acne vulgaris, psoriasis, burns, and wound healing. It has also been used in conjunction with surgical aesthetic and resurfacing procedures and has been reported to reduce erythema, edema, bruising, and days to healing. It’s been shown that PBMT stimulates fibroblast proliferation, collagen synthesis, and extracellular matrix resulting in lifting and tightening lax skin.

According to Dr. Anders, French dermatologists Linda Fouque, MD, and Michele Pelletier, MD, performed a series of in vivo and in vitro studies in which they tested the effects of yellow and red light for skin rejuvenation when used individually or in combination. “They found that fibroblasts and keratinocytes in vitro had great improvement in their morphology both with the yellow and red light, but the best improvement was seen with combination therapy,” Dr. Anders said. “This held true in their work looking at epidermal and dermal markers in the skin, where they found the best up-regulation in protein synthesis of such markers as collagens and fibronectin were produced when a combination wavelength light was used.”

Oral mucositis and pain

PBMT is also being used to treat oral mucositis (OM), a common adverse response to chemotherapy and/or radiation therapy, which causes pain, difficulty in swallowing and eating, and oral ulceration, and often interrupts the course of treatments. Authors of a recently published review on the risks and benefits of PBMT concluded that there is consistent evidence from a small number of high-quality studies that PBMT can help prevent the development of cancer therapy–induced OM, reduce pain intensity, as well as promote healing, and enhance patient quality of life.

“They also cautioned that, due to the limited long-term follow-up of patients, there is still concern for the potential long-term risks of PBMT in cancer cell mutation and amplification,” Dr. Anders said. “They advised that PBMT should be used carefully when the irradiation beam is in the direction of the tumor zone.”

Using PBMT for modulation of pain is another area of active research. Based on work from the laboratory of Dr. Anders and others, there are two methods to modulate pain. The first is to target tissue at irradiances below 100 mW/cm².

“In my laboratory, based on in vivo preclinical animal models of neuropathic pain, we used a 980-nm wavelength laser at 43.25 mW/cm² transcutaneously delivered to the level of the nerve for 20 seconds,” said Dr. Anders, who is a past president of the ASLMS. “Essentially, we found that the pain was modulated by reducing sensitivity to mechanical stimulation and also by causing an anti-inflammatory shift in microglial and macrophage phenotype in the dorsal root ganglion and spinal cord of affected segments.”

The second way to modulate pain, she continued, is to target tissue at irradiances above 250 mW/cm². She and her colleagues have conducted in vitro and in vivo studies, which indicate that treatment with an irradiance/fluence rate at 270 mW/cm² or higher at the nerve can rapidly block pain transmission.

“In vitro, we found that if we used an 810-nm wavelength light at 300 mW/cm², we got a disruption of microtubules in the DRG neurons in culture, specifically the small neurons, the nociceptive fibers, but we did not affect the proprioceptive fibers unless we increased the length of the treatment,” she said. “We essentially found the same thing in vivo in a rodent model of neuropathic pain.”

In a pilot study, Dr. Anders and coauthors examined the efficacy of laser irradiation of the dorsal root ganglion of the second lumbar spinal nerve for patients with chronic back pain.

They found that PBMT effectively reduced back pain equal to the effects of lidocaine.

Based on these two irradiation approaches of targeting tissue, Dr. Anders recommends that a combination therapy be used to modulate neuropathic pain going forward. “This approach would involve the initial use of a high-irradiance treatment [at least 250 mW/cm²] at the nerve to block the pain transmission,” she said. “That treatment would be followed by a series of low-irradiance treatments [10-100 mW/cm²] along the course of the involved nerve to alter chronic pathology and inflammation.”
 

Potential applications in neurology

Dr. Anders also discussed research efforts under way involving transcranial PBMT: the delivery of near-infrared light through the tissues of the scalp and skull to targeted brain regions to treat neurologic injuries and disorders. “There have been some exciting results in preclinical animal work and in small clinical pilot work that show that there could be possible beneficial effects in Parkinson’s disease, Alzheimer’s disease, depression, and improvement in cognition and memory after a brain injury, such as a TBI,” she said.

“Initially, though, there were a lot of questions about whether you could really deliver light to the brain through the scalp. In my laboratory, we used slices of nonfixed brain and found that the sulci within the human brain act as light-wave guides. We used an 808-nm near-infrared wavelength of light, so that the light could penetrate more deeply.” Using nonfixed cadaver heads, where the light was applied at the scalp surface, Dr. Anders and colleagues were able to measure photons down to the depth of 4 cm. “It’s generally agreed now, though, that it’s to a maximum depth of 2.5-3 cm that enough photons are delivered that would cause a beneficial therapeutic effect,” she said.

Dr. Anders disclosed that she has received equipment from LiteCure, grant funding from the Department of Defense, and that she holds advisory board roles with LiteCure and Neurothera. She has also served in leadership roles for the Optical Society and holds intellectual property rights for the Henry M. Jackson Foundation for the Advancement of Military Medicine.

dbrunk@mdedge.com

Advances in photobiomodulation have propelled the use of therapeutic applications in a variety of medical specialties, according to Juanita J. Anders, PhD.

During the annual conference of the American Society for Laser Medicine and Surgery, Dr. Anders, professor of anatomy, physiology, and genetics at the Uniformed Services University of the Health Sciences, Bethesda, Md., defined photobiomodulation (PBM) as the mechanism by which nonionizing optical radiation in the visible and near-infrared spectral range is absorbed by endogenous chromophores to elicit photophysical and photochemical events at various biological scales. Photobiomodulation therapy (PBMT) involves the use of light sources including lasers, LEDs, and broadband light, that emit visible and/or near-infrared light to cause physiological changes in cells and tissues and result in therapeutic benefits.

In dermatology, LED light therapy devices are commonly used for PBMT in wavelengths that range from blue (415 nm) and red (633 nm) to near infrared (830 nm). “Often, when PBMT is referred to by dermatologists it’s called LED therapy or LED light therapy,” Dr. Anders noted. “Some people are under the impression that this is different from PBMT. But remember: It’s not the device that’s producing the photons that is clinically relevant, but it’s the photons themselves. In both cases, the same radiances and fluence ranges are being used and the mechanisms are the same, so it’s all PBMT.”

The therapy is used to treat a wide variety of medical and aesthetic disorders including acne vulgaris, psoriasis, burns, and wound healing. It has also been used in conjunction with surgical aesthetic and resurfacing procedures and has been reported to reduce erythema, edema, bruising, and days to healing. It’s been shown that PBMT stimulates fibroblast proliferation, collagen synthesis, and extracellular matrix resulting in lifting and tightening lax skin.

According to Dr. Anders, French dermatologists Linda Fouque, MD, and Michele Pelletier, MD, performed a series of in vivo and in vitro studies in which they tested the effects of yellow and red light for skin rejuvenation when used individually or in combination. “They found that fibroblasts and keratinocytes in vitro had great improvement in their morphology both with the yellow and red light, but the best improvement was seen with combination therapy,” Dr. Anders said. “This held true in their work looking at epidermal and dermal markers in the skin, where they found the best up-regulation in protein synthesis of such markers as collagens and fibronectin were produced when a combination wavelength light was used.”

Oral mucositis and pain

PBMT is also being used to treat oral mucositis (OM), a common adverse response to chemotherapy and/or radiation therapy, which causes pain, difficulty in swallowing and eating, and oral ulceration, and often interrupts the course of treatments. Authors of a recently published review on the risks and benefits of PBMT concluded that there is consistent evidence from a small number of high-quality studies that PBMT can help prevent the development of cancer therapy–induced OM, reduce pain intensity, as well as promote healing, and enhance patient quality of life.

“They also cautioned that, due to the limited long-term follow-up of patients, there is still concern for the potential long-term risks of PBMT in cancer cell mutation and amplification,” Dr. Anders said. “They advised that PBMT should be used carefully when the irradiation beam is in the direction of the tumor zone.”

Using PBMT for modulation of pain is another area of active research. Based on work from the laboratory of Dr. Anders and others, there are two methods to modulate pain. The first is to target tissue at irradiances below 100 mW/cm².

“In my laboratory, based on in vivo preclinical animal models of neuropathic pain, we used a 980-nm wavelength laser at 43.25 mW/cm² transcutaneously delivered to the level of the nerve for 20 seconds,” said Dr. Anders, who is a past president of the ASLMS. “Essentially, we found that the pain was modulated by reducing sensitivity to mechanical stimulation and also by causing an anti-inflammatory shift in microglial and macrophage phenotype in the dorsal root ganglion and spinal cord of affected segments.”

The second way to modulate pain, she continued, is to target tissue at irradiances above 250 mW/cm². She and her colleagues have conducted in vitro and in vivo studies, which indicate that treatment with an irradiance/fluence rate at 270 mW/cm² or higher at the nerve can rapidly block pain transmission.

“In vitro, we found that if we used an 810-nm wavelength light at 300 mW/cm², we got a disruption of microtubules in the DRG neurons in culture, specifically the small neurons, the nociceptive fibers, but we did not affect the proprioceptive fibers unless we increased the length of the treatment,” she said. “We essentially found the same thing in vivo in a rodent model of neuropathic pain.”

In a pilot study, Dr. Anders and coauthors examined the efficacy of laser irradiation of the dorsal root ganglion of the second lumbar spinal nerve for patients with chronic back pain.

They found that PBMT effectively reduced back pain equal to the effects of lidocaine.

Based on these two irradiation approaches of targeting tissue, Dr. Anders recommends that a combination therapy be used to modulate neuropathic pain going forward. “This approach would involve the initial use of a high-irradiance treatment [at least 250 mW/cm²] at the nerve to block the pain transmission,” she said. “That treatment would be followed by a series of low-irradiance treatments [10-100 mW/cm²] along the course of the involved nerve to alter chronic pathology and inflammation.”
 

Potential applications in neurology

Dr. Anders also discussed research efforts under way involving transcranial PBMT: the delivery of near-infrared light through the tissues of the scalp and skull to targeted brain regions to treat neurologic injuries and disorders. “There have been some exciting results in preclinical animal work and in small clinical pilot work that show that there could be possible beneficial effects in Parkinson’s disease, Alzheimer’s disease, depression, and improvement in cognition and memory after a brain injury, such as a TBI,” she said.

“Initially, though, there were a lot of questions about whether you could really deliver light to the brain through the scalp. In my laboratory, we used slices of nonfixed brain and found that the sulci within the human brain act as light-wave guides. We used an 808-nm near-infrared wavelength of light, so that the light could penetrate more deeply.” Using nonfixed cadaver heads, where the light was applied at the scalp surface, Dr. Anders and colleagues were able to measure photons down to the depth of 4 cm. “It’s generally agreed now, though, that it’s to a maximum depth of 2.5-3 cm that enough photons are delivered that would cause a beneficial therapeutic effect,” she said.

Dr. Anders disclosed that she has received equipment from LiteCure, grant funding from the Department of Defense, and that she holds advisory board roles with LiteCure and Neurothera. She has also served in leadership roles for the Optical Society and holds intellectual property rights for the Henry M. Jackson Foundation for the Advancement of Military Medicine.

dbrunk@mdedge.com

Advances in photobiomodulation have propelled the use of therapeutic applications in a variety of medical specialties, according to Juanita J. Anders, PhD.

During the annual conference of the American Society for Laser Medicine and Surgery, Dr. Anders, professor of anatomy, physiology, and genetics at the Uniformed Services University of the Health Sciences, Bethesda, Md., defined photobiomodulation (PBM) as the mechanism by which nonionizing optical radiation in the visible and near-infrared spectral range is absorbed by endogenous chromophores to elicit photophysical and photochemical events at various biological scales. Photobiomodulation therapy (PBMT) involves the use of light sources including lasers, LEDs, and broadband light, that emit visible and/or near-infrared light to cause physiological changes in cells and tissues and result in therapeutic benefits.

In dermatology, LED light therapy devices are commonly used for PBMT in wavelengths that range from blue (415 nm) and red (633 nm) to near infrared (830 nm). “Often, when PBMT is referred to by dermatologists it’s called LED therapy or LED light therapy,” Dr. Anders noted. “Some people are under the impression that this is different from PBMT. But remember: It’s not the device that’s producing the photons that is clinically relevant, but it’s the photons themselves. In both cases, the same radiances and fluence ranges are being used and the mechanisms are the same, so it’s all PBMT.”

The therapy is used to treat a wide variety of medical and aesthetic disorders including acne vulgaris, psoriasis, burns, and wound healing. It has also been used in conjunction with surgical aesthetic and resurfacing procedures and has been reported to reduce erythema, edema, bruising, and days to healing. It’s been shown that PBMT stimulates fibroblast proliferation, collagen synthesis, and extracellular matrix resulting in lifting and tightening lax skin.

According to Dr. Anders, French dermatologists Linda Fouque, MD, and Michele Pelletier, MD, performed a series of in vivo and in vitro studies in which they tested the effects of yellow and red light for skin rejuvenation when used individually or in combination. “They found that fibroblasts and keratinocytes in vitro had great improvement in their morphology both with the yellow and red light, but the best improvement was seen with combination therapy,” Dr. Anders said. “This held true in their work looking at epidermal and dermal markers in the skin, where they found the best up-regulation in protein synthesis of such markers as collagens and fibronectin were produced when a combination wavelength light was used.”

Oral mucositis and pain

PBMT is also being used to treat oral mucositis (OM), a common adverse response to chemotherapy and/or radiation therapy, which causes pain, difficulty in swallowing and eating, and oral ulceration, and often interrupts the course of treatments. Authors of a recently published review on the risks and benefits of PBMT concluded that there is consistent evidence from a small number of high-quality studies that PBMT can help prevent the development of cancer therapy–induced OM, reduce pain intensity, as well as promote healing, and enhance patient quality of life.

“They also cautioned that, due to the limited long-term follow-up of patients, there is still concern for the potential long-term risks of PBMT in cancer cell mutation and amplification,” Dr. Anders said. “They advised that PBMT should be used carefully when the irradiation beam is in the direction of the tumor zone.”

Using PBMT for modulation of pain is another area of active research. Based on work from the laboratory of Dr. Anders and others, there are two methods to modulate pain. The first is to target tissue at irradiances below 100 mW/cm².

“In my laboratory, based on in vivo preclinical animal models of neuropathic pain, we used a 980-nm wavelength laser at 43.25 mW/cm² transcutaneously delivered to the level of the nerve for 20 seconds,” said Dr. Anders, who is a past president of the ASLMS. “Essentially, we found that the pain was modulated by reducing sensitivity to mechanical stimulation and also by causing an anti-inflammatory shift in microglial and macrophage phenotype in the dorsal root ganglion and spinal cord of affected segments.”

The second way to modulate pain, she continued, is to target tissue at irradiances above 250 mW/cm². She and her colleagues have conducted in vitro and in vivo studies, which indicate that treatment with an irradiance/fluence rate at 270 mW/cm² or higher at the nerve can rapidly block pain transmission.

“In vitro, we found that if we used an 810-nm wavelength light at 300 mW/cm², we got a disruption of microtubules in the DRG neurons in culture, specifically the small neurons, the nociceptive fibers, but we did not affect the proprioceptive fibers unless we increased the length of the treatment,” she said. “We essentially found the same thing in vivo in a rodent model of neuropathic pain.”

In a pilot study, Dr. Anders and coauthors examined the efficacy of laser irradiation of the dorsal root ganglion of the second lumbar spinal nerve for patients with chronic back pain.

They found that PBMT effectively reduced back pain equal to the effects of lidocaine.

Based on these two irradiation approaches of targeting tissue, Dr. Anders recommends that a combination therapy be used to modulate neuropathic pain going forward. “This approach would involve the initial use of a high-irradiance treatment [at least 250 mW/cm²] at the nerve to block the pain transmission,” she said. “That treatment would be followed by a series of low-irradiance treatments [10-100 mW/cm²] along the course of the involved nerve to alter chronic pathology and inflammation.”
 

Potential applications in neurology

Dr. Anders also discussed research efforts under way involving transcranial PBMT: the delivery of near-infrared light through the tissues of the scalp and skull to targeted brain regions to treat neurologic injuries and disorders. “There have been some exciting results in preclinical animal work and in small clinical pilot work that show that there could be possible beneficial effects in Parkinson’s disease, Alzheimer’s disease, depression, and improvement in cognition and memory after a brain injury, such as a TBI,” she said.

“Initially, though, there were a lot of questions about whether you could really deliver light to the brain through the scalp. In my laboratory, we used slices of nonfixed brain and found that the sulci within the human brain act as light-wave guides. We used an 808-nm near-infrared wavelength of light, so that the light could penetrate more deeply.” Using nonfixed cadaver heads, where the light was applied at the scalp surface, Dr. Anders and colleagues were able to measure photons down to the depth of 4 cm. “It’s generally agreed now, though, that it’s to a maximum depth of 2.5-3 cm that enough photons are delivered that would cause a beneficial therapeutic effect,” she said.

Dr. Anders disclosed that she has received equipment from LiteCure, grant funding from the Department of Defense, and that she holds advisory board roles with LiteCure and Neurothera. She has also served in leadership roles for the Optical Society and holds intellectual property rights for the Henry M. Jackson Foundation for the Advancement of Military Medicine.

dbrunk@mdedge.com

Quantitative assessment of the extent of interstitial lung disease in patients with systemic sclerosis and levels of certain proteins in bronchoalveolar lavage samples have potential for predicting mortality and disease progression, according to two analyses of data from the Scleroderma Lung Study I and II.

The analyses, presented at the annual European Congress of Rheumatology, aim to improve current prognostic abilities in patients with systemic sclerosis–interstitial lung disease (SSc-ILD). Although forced vital capacity is commonly used as a biomarker for survival in many SSc-ILD trials, other factors can affect FVC, such as respiratory muscle weakness and skin fibrosis. Further, FVC correlates poorly with patient-reported outcomes, explained first author Elizabeth Volkmann, MD, director of the scleroderma program at the University of California, Los Angeles, and the founder and codirector of the UCLA connective tissue disease–related interstitial lung disease program.

Dr. Volkmann presented two studies that investigated the potential of radiographic and protein biomarkers for predicting mortality and identifying patients at risk for ILD progression. The biomarkers may also help to identify patients who would benefit most from immunosuppressive therapy.

The first study found that tracking the quantitative extent of ILD (QILD) over time with high-resolution CT (HRCT) predicted poorer outcomes and could therefore act as a surrogate endpoint for mortality among patients with SSc-ILD. The other study identified associations between specific proteins from bronchoalveolar lavage (BAL) and the likelihood of ILD progression, although some associations were treatment dependent.

Jacob M. van Laar, MD, PhD, professor of rheumatology at the University Medical Center Utrecht (the Netherlands), who was not involved in the study, found the results intriguing and noted the importance of further validation in research before these biomarkers are considered for clinical use.

“It would be wonderful if we can tailor therapy based on BAL biomarkers in the future, as clinicians often struggle to decide on selection, timing, and duration of immunosuppressive treatment,” Dr. van Laar told this news organization. “This has become even more relevant with the introduction of new drugs such as nintedanib.”
 

Extent of ILD progression as a surrogate for mortality

Scleroderma Lung Study I involved 158 patients with SSc-ILD who were randomly assigned to receive either cyclophosphamide or placebo for 12 months. Scleroderma Lung Study II included 142 patients with SSc-ILD who were randomly assigned to receive either mycophenolate for 24 months or cyclophosphamide for 12 months followed by placebo for 12 months.

The researchers calculated QILD in the whole lung at baseline, at 12 months in the first trial, and at 24 months in the second trial. However, only 82 participants from the first trial and 90 participants from the second trial underwent HRCT. Demographic and disease characteristics were similar between the two groups on follow-up scans.

Follow-up continued for 12 years for patients in the first trial and 8 years in the second. The researchers compared survival rates between the 41% of participants from the first study and 31% of participants from the second study who had poorer QILD scores (at least a 2% increase) with the participants who had stable or improved scores (less than 2% increase).

Participants from both trials had significantly poorer long-term survival if their QILD scores had increased by at least 2% at follow-up (P = .01 for I; P = .019 for II). The association was no longer significant after adjustment for baseline FVC, age, and modified Rodnan skin score in the first trial (hazard ratio, 1.98; P = .089), but it remained significant for participants of the second trial (HR, 3.86; P = .014).

“Data from two independent trial cohorts demonstrated that radiographic progression of SSc-ILD at 1 and 2 years is associated with worse long-term survival,” Dr. Volkmann told attendees.

However, FVC did not significantly predict risk of mortality in either trial.

“To me, the most striking finding from the first study was that change in QILD performed better as a predictor of survival than change in FVC,” Dr. van Laar said in an interview. “This indicates QILD is fit for purpose and worth including in future clinical trials.”

Limitations of the study included lack of HRCT for all participants in the trials and the difference in timing (1 year and 2 years) of HRCT assessment between the two trials. The greater hazard ratio for worsened QILD in the second trial may suggest that assessment at 2 years provides more reliable data as a biomarker, Dr. Volkmann said.

“QILD may represent a better proxy for how a patient feels, functions, and survives than FVC,” she said.
 

Treatment-dependent biomarkers for worsening lung fibrosis

In the second study, the researchers looked for any associations between changes in the radiographic extent of SSc-ILD and 68 proteins from BAL.

“Being able to risk-stratify patients with interstitial lung disease at the time of diagnosis and predict which patients are likely to have a stable versus progressive disease course is critical for making important treatment decisions for these patients,” Dr. Volkmann told attendees.

The second study she presented involved Scleroderma Lung Study I. Of the 158 participants, 144 underwent a bronchoscopy, yielding BAL protein samples from 103 participants. The researchers determined the extent of radiographic fibrosis in the whole lung with quantitative imaging analysis of HRCT of the chest at baseline and 12 months.

Although the researchers identified several statistically significant associations between certain proteins and changes in radiographic fibrosis, “baseline protein levels were differentially associated with the course of ILD based on treatment status,” she told attendees.

For example, increased levels of the following proteins were linked to poor radiographic fibrosis scores for patients who received placebo:

• Granulocyte-macrophage colony-stimulating factor
• Interleukin-1
• Monocyte chemoattractant protein–3
• Chemokine ligand–5
• Transforming growth factor–beta
• Hepatocyte growth factor
• Stem cell factor
• IL-4
• TGF-alpha

Yet increases in these proteins predicted improvement in radiographic fibrosis in patients who had taken cyclophosphamide.

Independently of treatment, the researchers also identified an association between higher levels of fractalkine and poorer radiographic fibrosis scores and between higher IL-7 levels and improved radiographic fibrosis scores.

After adjusting for treatment arm and baseline severity of ILD, significant associations remained between change in radiographic fibrosis score and IL-1, MCP-3, surfactant protein C, IL-7 and CCL-5 levels.

“Biomarker discovery is really central to our ability to risk stratify patients with SSc-ILD,” Dr. Volkmann told attendees. “Understanding how biomarkers predict outcomes in treated and untreated patients may improve personalized medicine to patients with SSc-ILD and could also reveal novel treatment targets.”

Dr. van Laar said in an interview that this study’s biggest strength lay in its large sample size and in the comprehensiveness of the biomarkers studied.

“The findings are interesting from a research perspective and potentially relevant for clinical practice, but the utility of measuring biomarkers in BAL should be further studied for predictive value on clinical endpoints,” Dr. van Laar said. “BAL is an invasive procedure [that] is not routinely done.”

The research was funded by the National Institutes of Health. Dr. Volkmann has consulted for Boehringer Ingelheim and received grant funding from Corbus, Forbius, and Kadmon. Dr. van Laar has received grant funding or personal fees from Arthrogen, Arxx Therapeutics, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gesynta, Leadiant, Merck Sharp & Dohme, Roche, Sanofi, and Thermofisher.

A version of this article first appeared on Medscape.com.

Quantitative assessment of the extent of interstitial lung disease in patients with systemic sclerosis and levels of certain proteins in bronchoalveolar lavage samples have potential for predicting mortality and disease progression, according to two analyses of data from the Scleroderma Lung Study I and II.

The analyses, presented at the annual European Congress of Rheumatology, aim to improve current prognostic abilities in patients with systemic sclerosis–interstitial lung disease (SSc-ILD). Although forced vital capacity is commonly used as a biomarker for survival in many SSc-ILD trials, other factors can affect FVC, such as respiratory muscle weakness and skin fibrosis. Further, FVC correlates poorly with patient-reported outcomes, explained first author Elizabeth Volkmann, MD, director of the scleroderma program at the University of California, Los Angeles, and the founder and codirector of the UCLA connective tissue disease–related interstitial lung disease program.

Dr. Volkmann presented two studies that investigated the potential of radiographic and protein biomarkers for predicting mortality and identifying patients at risk for ILD progression. The biomarkers may also help to identify patients who would benefit most from immunosuppressive therapy.

The first study found that tracking the quantitative extent of ILD (QILD) over time with high-resolution CT (HRCT) predicted poorer outcomes and could therefore act as a surrogate endpoint for mortality among patients with SSc-ILD. The other study identified associations between specific proteins from bronchoalveolar lavage (BAL) and the likelihood of ILD progression, although some associations were treatment dependent.

Jacob M. van Laar, MD, PhD, professor of rheumatology at the University Medical Center Utrecht (the Netherlands), who was not involved in the study, found the results intriguing and noted the importance of further validation in research before these biomarkers are considered for clinical use.

“It would be wonderful if we can tailor therapy based on BAL biomarkers in the future, as clinicians often struggle to decide on selection, timing, and duration of immunosuppressive treatment,” Dr. van Laar told this news organization. “This has become even more relevant with the introduction of new drugs such as nintedanib.”
 

Extent of ILD progression as a surrogate for mortality

Scleroderma Lung Study I involved 158 patients with SSc-ILD who were randomly assigned to receive either cyclophosphamide or placebo for 12 months. Scleroderma Lung Study II included 142 patients with SSc-ILD who were randomly assigned to receive either mycophenolate for 24 months or cyclophosphamide for 12 months followed by placebo for 12 months.

The researchers calculated QILD in the whole lung at baseline, at 12 months in the first trial, and at 24 months in the second trial. However, only 82 participants from the first trial and 90 participants from the second trial underwent HRCT. Demographic and disease characteristics were similar between the two groups on follow-up scans.

Follow-up continued for 12 years for patients in the first trial and 8 years in the second. The researchers compared survival rates between the 41% of participants from the first study and 31% of participants from the second study who had poorer QILD scores (at least a 2% increase) with the participants who had stable or improved scores (less than 2% increase).

Participants from both trials had significantly poorer long-term survival if their QILD scores had increased by at least 2% at follow-up (P = .01 for I; P = .019 for II). The association was no longer significant after adjustment for baseline FVC, age, and modified Rodnan skin score in the first trial (hazard ratio, 1.98; P = .089), but it remained significant for participants of the second trial (HR, 3.86; P = .014).

“Data from two independent trial cohorts demonstrated that radiographic progression of SSc-ILD at 1 and 2 years is associated with worse long-term survival,” Dr. Volkmann told attendees.

However, FVC did not significantly predict risk of mortality in either trial.

“To me, the most striking finding from the first study was that change in QILD performed better as a predictor of survival than change in FVC,” Dr. van Laar said in an interview. “This indicates QILD is fit for purpose and worth including in future clinical trials.”

Limitations of the study included lack of HRCT for all participants in the trials and the difference in timing (1 year and 2 years) of HRCT assessment between the two trials. The greater hazard ratio for worsened QILD in the second trial may suggest that assessment at 2 years provides more reliable data as a biomarker, Dr. Volkmann said.

“QILD may represent a better proxy for how a patient feels, functions, and survives than FVC,” she said.
 

Treatment-dependent biomarkers for worsening lung fibrosis

In the second study, the researchers looked for any associations between changes in the radiographic extent of SSc-ILD and 68 proteins from BAL.

“Being able to risk-stratify patients with interstitial lung disease at the time of diagnosis and predict which patients are likely to have a stable versus progressive disease course is critical for making important treatment decisions for these patients,” Dr. Volkmann told attendees.

The second study she presented involved Scleroderma Lung Study I. Of the 158 participants, 144 underwent a bronchoscopy, yielding BAL protein samples from 103 participants. The researchers determined the extent of radiographic fibrosis in the whole lung with quantitative imaging analysis of HRCT of the chest at baseline and 12 months.

Although the researchers identified several statistically significant associations between certain proteins and changes in radiographic fibrosis, “baseline protein levels were differentially associated with the course of ILD based on treatment status,” she told attendees.

For example, increased levels of the following proteins were linked to poor radiographic fibrosis scores for patients who received placebo:

• Granulocyte-macrophage colony-stimulating factor
• Interleukin-1
• Monocyte chemoattractant protein–3
• Chemokine ligand–5
• Transforming growth factor–beta
• Hepatocyte growth factor
• Stem cell factor
• IL-4
• TGF-alpha

Yet increases in these proteins predicted improvement in radiographic fibrosis in patients who had taken cyclophosphamide.

Independently of treatment, the researchers also identified an association between higher levels of fractalkine and poorer radiographic fibrosis scores and between higher IL-7 levels and improved radiographic fibrosis scores.

After adjusting for treatment arm and baseline severity of ILD, significant associations remained between change in radiographic fibrosis score and IL-1, MCP-3, surfactant protein C, IL-7 and CCL-5 levels.

“Biomarker discovery is really central to our ability to risk stratify patients with SSc-ILD,” Dr. Volkmann told attendees. “Understanding how biomarkers predict outcomes in treated and untreated patients may improve personalized medicine to patients with SSc-ILD and could also reveal novel treatment targets.”

Dr. van Laar said in an interview that this study’s biggest strength lay in its large sample size and in the comprehensiveness of the biomarkers studied.

“The findings are interesting from a research perspective and potentially relevant for clinical practice, but the utility of measuring biomarkers in BAL should be further studied for predictive value on clinical endpoints,” Dr. van Laar said. “BAL is an invasive procedure [that] is not routinely done.”

The research was funded by the National Institutes of Health. Dr. Volkmann has consulted for Boehringer Ingelheim and received grant funding from Corbus, Forbius, and Kadmon. Dr. van Laar has received grant funding or personal fees from Arthrogen, Arxx Therapeutics, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gesynta, Leadiant, Merck Sharp & Dohme, Roche, Sanofi, and Thermofisher.

A version of this article first appeared on Medscape.com.

Quantitative assessment of the extent of interstitial lung disease in patients with systemic sclerosis and levels of certain proteins in bronchoalveolar lavage samples have potential for predicting mortality and disease progression, according to two analyses of data from the Scleroderma Lung Study I and II.

The analyses, presented at the annual European Congress of Rheumatology, aim to improve current prognostic abilities in patients with systemic sclerosis–interstitial lung disease (SSc-ILD). Although forced vital capacity is commonly used as a biomarker for survival in many SSc-ILD trials, other factors can affect FVC, such as respiratory muscle weakness and skin fibrosis. Further, FVC correlates poorly with patient-reported outcomes, explained first author Elizabeth Volkmann, MD, director of the scleroderma program at the University of California, Los Angeles, and the founder and codirector of the UCLA connective tissue disease–related interstitial lung disease program.

Dr. Volkmann presented two studies that investigated the potential of radiographic and protein biomarkers for predicting mortality and identifying patients at risk for ILD progression. The biomarkers may also help to identify patients who would benefit most from immunosuppressive therapy.

The first study found that tracking the quantitative extent of ILD (QILD) over time with high-resolution CT (HRCT) predicted poorer outcomes and could therefore act as a surrogate endpoint for mortality among patients with SSc-ILD. The other study identified associations between specific proteins from bronchoalveolar lavage (BAL) and the likelihood of ILD progression, although some associations were treatment dependent.

Jacob M. van Laar, MD, PhD, professor of rheumatology at the University Medical Center Utrecht (the Netherlands), who was not involved in the study, found the results intriguing and noted the importance of further validation in research before these biomarkers are considered for clinical use.

“It would be wonderful if we can tailor therapy based on BAL biomarkers in the future, as clinicians often struggle to decide on selection, timing, and duration of immunosuppressive treatment,” Dr. van Laar told this news organization. “This has become even more relevant with the introduction of new drugs such as nintedanib.”
 

Extent of ILD progression as a surrogate for mortality

Scleroderma Lung Study I involved 158 patients with SSc-ILD who were randomly assigned to receive either cyclophosphamide or placebo for 12 months. Scleroderma Lung Study II included 142 patients with SSc-ILD who were randomly assigned to receive either mycophenolate for 24 months or cyclophosphamide for 12 months followed by placebo for 12 months.

The researchers calculated QILD in the whole lung at baseline, at 12 months in the first trial, and at 24 months in the second trial. However, only 82 participants from the first trial and 90 participants from the second trial underwent HRCT. Demographic and disease characteristics were similar between the two groups on follow-up scans.

Follow-up continued for 12 years for patients in the first trial and 8 years in the second. The researchers compared survival rates between the 41% of participants from the first study and 31% of participants from the second study who had poorer QILD scores (at least a 2% increase) with the participants who had stable or improved scores (less than 2% increase).

Participants from both trials had significantly poorer long-term survival if their QILD scores had increased by at least 2% at follow-up (P = .01 for I; P = .019 for II). The association was no longer significant after adjustment for baseline FVC, age, and modified Rodnan skin score in the first trial (hazard ratio, 1.98; P = .089), but it remained significant for participants of the second trial (HR, 3.86; P = .014).

“Data from two independent trial cohorts demonstrated that radiographic progression of SSc-ILD at 1 and 2 years is associated with worse long-term survival,” Dr. Volkmann told attendees.

However, FVC did not significantly predict risk of mortality in either trial.

“To me, the most striking finding from the first study was that change in QILD performed better as a predictor of survival than change in FVC,” Dr. van Laar said in an interview. “This indicates QILD is fit for purpose and worth including in future clinical trials.”

Limitations of the study included lack of HRCT for all participants in the trials and the difference in timing (1 year and 2 years) of HRCT assessment between the two trials. The greater hazard ratio for worsened QILD in the second trial may suggest that assessment at 2 years provides more reliable data as a biomarker, Dr. Volkmann said.

“QILD may represent a better proxy for how a patient feels, functions, and survives than FVC,” she said.
 

Treatment-dependent biomarkers for worsening lung fibrosis

In the second study, the researchers looked for any associations between changes in the radiographic extent of SSc-ILD and 68 proteins from BAL.

“Being able to risk-stratify patients with interstitial lung disease at the time of diagnosis and predict which patients are likely to have a stable versus progressive disease course is critical for making important treatment decisions for these patients,” Dr. Volkmann told attendees.

The second study she presented involved Scleroderma Lung Study I. Of the 158 participants, 144 underwent a bronchoscopy, yielding BAL protein samples from 103 participants. The researchers determined the extent of radiographic fibrosis in the whole lung with quantitative imaging analysis of HRCT of the chest at baseline and 12 months.

Although the researchers identified several statistically significant associations between certain proteins and changes in radiographic fibrosis, “baseline protein levels were differentially associated with the course of ILD based on treatment status,” she told attendees.

For example, increased levels of the following proteins were linked to poor radiographic fibrosis scores for patients who received placebo:

• Granulocyte-macrophage colony-stimulating factor
• Interleukin-1
• Monocyte chemoattractant protein–3
• Chemokine ligand–5
• Transforming growth factor–beta
• Hepatocyte growth factor
• Stem cell factor
• IL-4
• TGF-alpha

Yet increases in these proteins predicted improvement in radiographic fibrosis in patients who had taken cyclophosphamide.

Independently of treatment, the researchers also identified an association between higher levels of fractalkine and poorer radiographic fibrosis scores and between higher IL-7 levels and improved radiographic fibrosis scores.

After adjusting for treatment arm and baseline severity of ILD, significant associations remained between change in radiographic fibrosis score and IL-1, MCP-3, surfactant protein C, IL-7 and CCL-5 levels.

“Biomarker discovery is really central to our ability to risk stratify patients with SSc-ILD,” Dr. Volkmann told attendees. “Understanding how biomarkers predict outcomes in treated and untreated patients may improve personalized medicine to patients with SSc-ILD and could also reveal novel treatment targets.”

Dr. van Laar said in an interview that this study’s biggest strength lay in its large sample size and in the comprehensiveness of the biomarkers studied.

“The findings are interesting from a research perspective and potentially relevant for clinical practice, but the utility of measuring biomarkers in BAL should be further studied for predictive value on clinical endpoints,” Dr. van Laar said. “BAL is an invasive procedure [that] is not routinely done.”

The research was funded by the National Institutes of Health. Dr. Volkmann has consulted for Boehringer Ingelheim and received grant funding from Corbus, Forbius, and Kadmon. Dr. van Laar has received grant funding or personal fees from Arthrogen, Arxx Therapeutics, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gesynta, Leadiant, Merck Sharp & Dohme, Roche, Sanofi, and Thermofisher.

A version of this article first appeared on Medscape.com.

Diets high in red meats, saturated fats, and sugars, relative to diets dominated by fruits, vegetables, and legumes, are associated with an increased risk of gout independent of an underlying genetic risk, according to independent sets of data presented at the annual European Congress of Rheumatology.

Only one of the two retrospective analyses evaluated diet in the context of a genetic risk score, but “no evidence of an additional or multiplicative interaction” was seen when genetic risk was evaluated on top of the risk already known to be associated with a Western diet, reported Chio Yokose, MD, a researcher and clinician in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston.

A parallel study presented at the EULAR Congress looked at the impact of a proinflammatory diet. Although genetic predisposition was not considered in this analysis, this diet, too, was associated with increased risk of gout independent of a long list of other variables. Each of the studies supports the potential for diet to be a target for risk reduction.

“Adhering to a diet with low inflammatory potential may mediate systemic and metabolic inflammation,” reported Natalie McCormick, PhD, a research fellow at Massachusetts General Hospital. She said the association of an inflammatory diet with gout is analogous to previous studies linking this type of diet to type 2 diabetes mellitus and cardiovascular disease because the inflammatory response is a pathogenic factor.

The two retrospective studies evaluated different but overlapping sets of data. Dr. Yokose and Dr. McCormick collaborated on both studies.

In the study of Western diet, which was restricted to women, the focus was on both diet and genes. Using food frequency questionnaires completed by 18,512 women participating in the Nurses’ Health Study (NHS), subjects were placed in quintiles for relative exposure to Western diets and for an interventional diet called DASH (Dietary Approaches to Stop Hypertension) that is high in fruits and vegetables.

A genetic risk score (GRS) was developed for participants using 114 serum urate single-nucleotide polymorphisms from a genomewide association study.

For the Western diet, there was a stepwise increased risk of gout per quintile associated with greater exposure. For the DASH diet, the same phenomenon was seen in reverse so that risk of gout was incrementally lower per quintile defining greater adherence.

When considered as a variable, GRS altered these basic relationships only for the DASH diet. After adjusting for multiple factors, such as age, menopause, use of hormone therapy, and hypertension, there was no significant interaction observed for genetic predisposition in relation to the Western diet.

For the DASH diet, there was an even greater reduction in the relative risk of gout among those with a high GRS if they were in the quintile defining greatest adherence to the DASH diet. Although this association fell just short of reaching statistical significance (P = .056), Dr. Yokose indicated that it was a strong trend.

Gout similarly associated with proinflammatory diet

The proinflammatory diet shares many food items with the Western diet, including refined carbohydrates, sweetened beverages, red meat, and fried foods. The study that evaluated its impact used dietary history collected from in 164,090 women in the NHS and 40,598 men in the Health Professionals Follow-up Study. In both, participants completed dietary questionnaires every 4 years. Patients were assigned an Empirical Dietary Index of Inflammatory Potential (EDIP) score on the basis of these questionnaires.

When the 2,874 incident gout cases were evaluated by EDIP quintile, those in the highest had a 50% greater risk of gout than did those in the lowest when adjusted for multiple potential confounders. When stratified by intake of alcohol, the impact of being in the highest quintile of inflammatory diet was even greater, producing a 2.37-fold increased risk of gout.
 

Impact of weight on risk for gout

The impact of proinflammatory diet was detectable even after adjusting for adiposity, a gout risk factor reconfirmed in a third study presented at EULAR by this same team of investigators. In that study, presented by Dr. Yokose, a GRS above the mean was associated with a further increased likelihood of gout among those with elevated body mass index. However, obesity remained a risk factor for gout even among those with a low GRS.

copyright joloei/Thinkstock

The data from this study indicate “maintaining healthy weight is an important gout prevention strategy, regardless of underlying genetic risk,” Dr. Yokose reported.

All three studies reinforce diet as a modifiable risk factor for gout. According to both Dr. Yokose and Dr. McCormick, healthy diets should be considered as a gout prevention strategy.

Annelies Boonen, MD, PhD, professor of internal medicine (rheumatology) at the University of Maastricht (the Netherlands), did not challenge these conclusions. However, she cautioned that it is “very difficult to evaluate food questionnaires.” She further noted that retrospective analyses complicate efforts to control for the many potential confounders.

Ultimately, healthy diets can be recommended for many reasons, particularly in individuals with other risk factors for gout. For this reason, Dr. Boonen indicated that it will be difficult to prove definitively that gout can be prevented by avoiding Western diets and other diets high in proinflammatory foods. However, definitive proof of this benefit might not be essential for the purpose of a general recommendation to eat healthy foods.

Dr. Yokose and Dr. McCormick reported no potential conflicts of interest.

Diets high in red meats, saturated fats, and sugars, relative to diets dominated by fruits, vegetables, and legumes, are associated with an increased risk of gout independent of an underlying genetic risk, according to independent sets of data presented at the annual European Congress of Rheumatology.

Only one of the two retrospective analyses evaluated diet in the context of a genetic risk score, but “no evidence of an additional or multiplicative interaction” was seen when genetic risk was evaluated on top of the risk already known to be associated with a Western diet, reported Chio Yokose, MD, a researcher and clinician in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston.

A parallel study presented at the EULAR Congress looked at the impact of a proinflammatory diet. Although genetic predisposition was not considered in this analysis, this diet, too, was associated with increased risk of gout independent of a long list of other variables. Each of the studies supports the potential for diet to be a target for risk reduction.

“Adhering to a diet with low inflammatory potential may mediate systemic and metabolic inflammation,” reported Natalie McCormick, PhD, a research fellow at Massachusetts General Hospital. She said the association of an inflammatory diet with gout is analogous to previous studies linking this type of diet to type 2 diabetes mellitus and cardiovascular disease because the inflammatory response is a pathogenic factor.

The two retrospective studies evaluated different but overlapping sets of data. Dr. Yokose and Dr. McCormick collaborated on both studies.

In the study of Western diet, which was restricted to women, the focus was on both diet and genes. Using food frequency questionnaires completed by 18,512 women participating in the Nurses’ Health Study (NHS), subjects were placed in quintiles for relative exposure to Western diets and for an interventional diet called DASH (Dietary Approaches to Stop Hypertension) that is high in fruits and vegetables.

A genetic risk score (GRS) was developed for participants using 114 serum urate single-nucleotide polymorphisms from a genomewide association study.

For the Western diet, there was a stepwise increased risk of gout per quintile associated with greater exposure. For the DASH diet, the same phenomenon was seen in reverse so that risk of gout was incrementally lower per quintile defining greater adherence.

When considered as a variable, GRS altered these basic relationships only for the DASH diet. After adjusting for multiple factors, such as age, menopause, use of hormone therapy, and hypertension, there was no significant interaction observed for genetic predisposition in relation to the Western diet.

For the DASH diet, there was an even greater reduction in the relative risk of gout among those with a high GRS if they were in the quintile defining greatest adherence to the DASH diet. Although this association fell just short of reaching statistical significance (P = .056), Dr. Yokose indicated that it was a strong trend.

Gout similarly associated with proinflammatory diet

The proinflammatory diet shares many food items with the Western diet, including refined carbohydrates, sweetened beverages, red meat, and fried foods. The study that evaluated its impact used dietary history collected from in 164,090 women in the NHS and 40,598 men in the Health Professionals Follow-up Study. In both, participants completed dietary questionnaires every 4 years. Patients were assigned an Empirical Dietary Index of Inflammatory Potential (EDIP) score on the basis of these questionnaires.

When the 2,874 incident gout cases were evaluated by EDIP quintile, those in the highest had a 50% greater risk of gout than did those in the lowest when adjusted for multiple potential confounders. When stratified by intake of alcohol, the impact of being in the highest quintile of inflammatory diet was even greater, producing a 2.37-fold increased risk of gout.
 

Impact of weight on risk for gout

The impact of proinflammatory diet was detectable even after adjusting for adiposity, a gout risk factor reconfirmed in a third study presented at EULAR by this same team of investigators. In that study, presented by Dr. Yokose, a GRS above the mean was associated with a further increased likelihood of gout among those with elevated body mass index. However, obesity remained a risk factor for gout even among those with a low GRS.

copyright joloei/Thinkstock

The data from this study indicate “maintaining healthy weight is an important gout prevention strategy, regardless of underlying genetic risk,” Dr. Yokose reported.

All three studies reinforce diet as a modifiable risk factor for gout. According to both Dr. Yokose and Dr. McCormick, healthy diets should be considered as a gout prevention strategy.

Annelies Boonen, MD, PhD, professor of internal medicine (rheumatology) at the University of Maastricht (the Netherlands), did not challenge these conclusions. However, she cautioned that it is “very difficult to evaluate food questionnaires.” She further noted that retrospective analyses complicate efforts to control for the many potential confounders.

Ultimately, healthy diets can be recommended for many reasons, particularly in individuals with other risk factors for gout. For this reason, Dr. Boonen indicated that it will be difficult to prove definitively that gout can be prevented by avoiding Western diets and other diets high in proinflammatory foods. However, definitive proof of this benefit might not be essential for the purpose of a general recommendation to eat healthy foods.

Dr. Yokose and Dr. McCormick reported no potential conflicts of interest.

Diets high in red meats, saturated fats, and sugars, relative to diets dominated by fruits, vegetables, and legumes, are associated with an increased risk of gout independent of an underlying genetic risk, according to independent sets of data presented at the annual European Congress of Rheumatology.

Only one of the two retrospective analyses evaluated diet in the context of a genetic risk score, but “no evidence of an additional or multiplicative interaction” was seen when genetic risk was evaluated on top of the risk already known to be associated with a Western diet, reported Chio Yokose, MD, a researcher and clinician in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston.

A parallel study presented at the EULAR Congress looked at the impact of a proinflammatory diet. Although genetic predisposition was not considered in this analysis, this diet, too, was associated with increased risk of gout independent of a long list of other variables. Each of the studies supports the potential for diet to be a target for risk reduction.

“Adhering to a diet with low inflammatory potential may mediate systemic and metabolic inflammation,” reported Natalie McCormick, PhD, a research fellow at Massachusetts General Hospital. She said the association of an inflammatory diet with gout is analogous to previous studies linking this type of diet to type 2 diabetes mellitus and cardiovascular disease because the inflammatory response is a pathogenic factor.

The two retrospective studies evaluated different but overlapping sets of data. Dr. Yokose and Dr. McCormick collaborated on both studies.

In the study of Western diet, which was restricted to women, the focus was on both diet and genes. Using food frequency questionnaires completed by 18,512 women participating in the Nurses’ Health Study (NHS), subjects were placed in quintiles for relative exposure to Western diets and for an interventional diet called DASH (Dietary Approaches to Stop Hypertension) that is high in fruits and vegetables.

A genetic risk score (GRS) was developed for participants using 114 serum urate single-nucleotide polymorphisms from a genomewide association study.

For the Western diet, there was a stepwise increased risk of gout per quintile associated with greater exposure. For the DASH diet, the same phenomenon was seen in reverse so that risk of gout was incrementally lower per quintile defining greater adherence.

When considered as a variable, GRS altered these basic relationships only for the DASH diet. After adjusting for multiple factors, such as age, menopause, use of hormone therapy, and hypertension, there was no significant interaction observed for genetic predisposition in relation to the Western diet.

For the DASH diet, there was an even greater reduction in the relative risk of gout among those with a high GRS if they were in the quintile defining greatest adherence to the DASH diet. Although this association fell just short of reaching statistical significance (P = .056), Dr. Yokose indicated that it was a strong trend.

Gout similarly associated with proinflammatory diet

The proinflammatory diet shares many food items with the Western diet, including refined carbohydrates, sweetened beverages, red meat, and fried foods. The study that evaluated its impact used dietary history collected from in 164,090 women in the NHS and 40,598 men in the Health Professionals Follow-up Study. In both, participants completed dietary questionnaires every 4 years. Patients were assigned an Empirical Dietary Index of Inflammatory Potential (EDIP) score on the basis of these questionnaires.

When the 2,874 incident gout cases were evaluated by EDIP quintile, those in the highest had a 50% greater risk of gout than did those in the lowest when adjusted for multiple potential confounders. When stratified by intake of alcohol, the impact of being in the highest quintile of inflammatory diet was even greater, producing a 2.37-fold increased risk of gout.
 

Impact of weight on risk for gout

The impact of proinflammatory diet was detectable even after adjusting for adiposity, a gout risk factor reconfirmed in a third study presented at EULAR by this same team of investigators. In that study, presented by Dr. Yokose, a GRS above the mean was associated with a further increased likelihood of gout among those with elevated body mass index. However, obesity remained a risk factor for gout even among those with a low GRS.

copyright joloei/Thinkstock

The data from this study indicate “maintaining healthy weight is an important gout prevention strategy, regardless of underlying genetic risk,” Dr. Yokose reported.

All three studies reinforce diet as a modifiable risk factor for gout. According to both Dr. Yokose and Dr. McCormick, healthy diets should be considered as a gout prevention strategy.

Annelies Boonen, MD, PhD, professor of internal medicine (rheumatology) at the University of Maastricht (the Netherlands), did not challenge these conclusions. However, she cautioned that it is “very difficult to evaluate food questionnaires.” She further noted that retrospective analyses complicate efforts to control for the many potential confounders.

Ultimately, healthy diets can be recommended for many reasons, particularly in individuals with other risk factors for gout. For this reason, Dr. Boonen indicated that it will be difficult to prove definitively that gout can be prevented by avoiding Western diets and other diets high in proinflammatory foods. However, definitive proof of this benefit might not be essential for the purpose of a general recommendation to eat healthy foods.

Dr. Yokose and Dr. McCormick reported no potential conflicts of interest.

Even the youngest patients with relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL) may be able to benefit from chimeric antigen reception T-cell (CAR T) therapy, investigators in an international consortium say.

Among 30 children aged under 2 years at the time of (B-ALL diagnosis, manufacturing of the CAR T product tisagenlecleucel (Kymriah) was feasible in 28 patients, and treatment resulted in high rates of minimal residual disease (MRD) negativity, complete responses, event-free survival, and overall survival, reported Sara Ghorashian, MD from the University College London Great Ormond Street Institute of Child Health, on behalf of the International BFM Resistant Disease Committee.

“The disease-related outcomes noted in this cohort of younger children predominantly with relapsed/refractory infant [mixed lineage leukemia]–rearranged ALL were at least as good as for the ELIANA study,” she said in an oral abstract presented during the European Hematology Association annual congress (Abstract S116).

The international, single-arm, open-label, ELIANA study was a phase 2 trial that included 97 patients aged 3-24 years with relapsed or refractory B-cell ALL, most of whom had previously undergone a hematopoietic stem cell transplant. Of those patients, 79 patients went on to receive a single infusion of the CAR T therapy.

“It’s fantastic data,” said Kevin J. Curran, MD, a pediatric hematologist/oncologist specializing in stem cell transplants and cellular therapy at Memorial Sloan Kettering Cancer Center, New York.

“Pediatric leukemia, while it’s the most common malignancy that happens in children, when you get down to this really small group, this under 3-year-old group, it’s hard to get a cohort, and for them to put together 30 patients, and show these great results is groundbreaking,” he said in an interview.

“Most importantly, it gives hope to parents who have young children who have really difficult to treat leukemia,” he said.

Dr. Curran was not involved in the study.
 

Scarce data on ALL in infants

“Children under 3 years of age were excluded from the ELIANA study, yet in terms of having often highly aggressive disease, with traditionally poor outcomes with conventional therapy, the need for novel forms of therapy for children with relapsed infant ALL is important,” Dr. Ghorashian said.

Because there is a paucity of data on outcomes in the youngest children, some health authorities will not support the use of tisagenlecleucel in this age group, and there are concerns about difficulties with performing leukapheresis in children weighing less than 10 kg, she noted.

To gain a better understanding of outcomes, members of the International BFM (Berlin-Frankfurt-Munster) Study Group conducted a retrospective analysis of data on all patients assessed for tisagenlecleucel for B-ALL who were aged under 3 years at screening at 1 of 15 centers in Europe and Israel.

A total of 30 patients were screened and had T cells harvested. Of this group, three patients did not receive CAR T infusions, two because of manufacturing failures, and one because of progressive disease.

Of the 27 patients who received CAR T infusions, 26 were evaluable for disease outcomes (1 had yet to reach the 30-day post infusion at the time of data cutoff).

The median age at diagnosis was 4.4 months, and the median age at infusion was 17.4 months; 19 of the 30 children in the entire cohort were boys. Mixed lineage leukemia rearrangements were found in 24 children, and 21 had undergone a stem cell transplant.

The children had a median of two prior lines of therapy, not including transplant. Seven of the children had received inotuzumab (Besponsa) and 11 had received blinotumumab (Blincyto).
 

High success rate

Of the 27 patients infused, 17 had sufficient cells harvested in a single day, and the remainder required 2-4 days. As noted, the CAR T product was successfully manufactured in 28 patients, with a median dose of 2.3 x 10⁶/kg of patient weight.

The treatment failed for 2 of the 26 efficacy-evaluable patients, resulting in an MRD-negative rate of 92%.

Event-free survival at 6 months was 67%, similar to that in ELIANA (73%), and the 12-month event-free survival was 58%, which was superior to that in ELIANA (50%).

The 6-month and 12-month overall survival rates among the younger children were identical at 88%, compared with 90% and 76%, respectively, in ELIANA.

The 6- and 12-month probability of ongoing B-cell depletion, indicating CAR T persistence, were 77% and 68%, respectively. In ELIANA, the 6-month probability of B-cell depletion was 83%.

A total of 10 of the 27 patients received further therapy, including 3 who were given maintenance therapy for poor CAR T persistence, 2 who underwent chemotherapy for relapse, and 5 who underwent allogeneic stem cell transplant.

Of six patients who experienced a relapse after having a complete response, two had CD19 relapse.
 

Low rate of serious CRS

At 30 days post infusion, grade 3 or greater cytokine release syndrome (CRS) had occurred in two patients, severe neurotoxicity occurred in one, and grade 3 or greater prolonged cytopenias occurred in eight patients.

The toxicity profile in this study was generally favorable in comparison with ELIANA, with shorter median duration of CRS, shorter median duration of CRS-related ICU stay, and a lower frequency of tocilizumab use. It should be noted, however, that the I-BFM investigators used American Society for Transplantation and Cellular Therapy CRS consenus criteria, whereas the ELIANA investigators used University of Pennsylvania criteria.

“If the longer-term follow-up data are encouraging, it might suggest that the outcomes from tisagenlecleucel therapy are comparable to that of stem cell transplantation in high-risk relapsed infant ALL, without the associated late effects, and possibly supports CAR T-cell therapy eventually replace stem cell transplantation in this setting,” Dr. Ghorashian said.

Dr. Curran, who leads the CAR T effort at MSK Kids, the children’s division of MSKCC, agreed that the goal is for CAR T to replace stem cell transplants.

“I hope I put my clinical practice out of business with my research practice,” he said, but added that “I think we need to do more research in figuring out how to best use CAR T cells, either earlier, or as some data suggest, by treating patients with lower disease burden we would get better durability.

“Because obviously in kids’ cancer one relapse is too much, and we want to be able to raise that bar and provide hope and a cure for all of our children,” he said.

The study was sponsored by the I-BFM Resistant Disease Committee and member institutions. Dr. Ghorashian disclosed advisory board activity for Novartis, maker of tisagenlecleucel, and patents and royalties from UCL Business. Dr. Curran research funding and consulting fees from Novartis.

Even the youngest patients with relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL) may be able to benefit from chimeric antigen reception T-cell (CAR T) therapy, investigators in an international consortium say.

Among 30 children aged under 2 years at the time of (B-ALL diagnosis, manufacturing of the CAR T product tisagenlecleucel (Kymriah) was feasible in 28 patients, and treatment resulted in high rates of minimal residual disease (MRD) negativity, complete responses, event-free survival, and overall survival, reported Sara Ghorashian, MD from the University College London Great Ormond Street Institute of Child Health, on behalf of the International BFM Resistant Disease Committee.

“The disease-related outcomes noted in this cohort of younger children predominantly with relapsed/refractory infant [mixed lineage leukemia]–rearranged ALL were at least as good as for the ELIANA study,” she said in an oral abstract presented during the European Hematology Association annual congress (Abstract S116).

The international, single-arm, open-label, ELIANA study was a phase 2 trial that included 97 patients aged 3-24 years with relapsed or refractory B-cell ALL, most of whom had previously undergone a hematopoietic stem cell transplant. Of those patients, 79 patients went on to receive a single infusion of the CAR T therapy.

“It’s fantastic data,” said Kevin J. Curran, MD, a pediatric hematologist/oncologist specializing in stem cell transplants and cellular therapy at Memorial Sloan Kettering Cancer Center, New York.

“Pediatric leukemia, while it’s the most common malignancy that happens in children, when you get down to this really small group, this under 3-year-old group, it’s hard to get a cohort, and for them to put together 30 patients, and show these great results is groundbreaking,” he said in an interview.

“Most importantly, it gives hope to parents who have young children who have really difficult to treat leukemia,” he said.

Dr. Curran was not involved in the study.
 

Scarce data on ALL in infants

“Children under 3 years of age were excluded from the ELIANA study, yet in terms of having often highly aggressive disease, with traditionally poor outcomes with conventional therapy, the need for novel forms of therapy for children with relapsed infant ALL is important,” Dr. Ghorashian said.

Because there is a paucity of data on outcomes in the youngest children, some health authorities will not support the use of tisagenlecleucel in this age group, and there are concerns about difficulties with performing leukapheresis in children weighing less than 10 kg, she noted.

To gain a better understanding of outcomes, members of the International BFM (Berlin-Frankfurt-Munster) Study Group conducted a retrospective analysis of data on all patients assessed for tisagenlecleucel for B-ALL who were aged under 3 years at screening at 1 of 15 centers in Europe and Israel.

A total of 30 patients were screened and had T cells harvested. Of this group, three patients did not receive CAR T infusions, two because of manufacturing failures, and one because of progressive disease.

Of the 27 patients who received CAR T infusions, 26 were evaluable for disease outcomes (1 had yet to reach the 30-day post infusion at the time of data cutoff).

The median age at diagnosis was 4.4 months, and the median age at infusion was 17.4 months; 19 of the 30 children in the entire cohort were boys. Mixed lineage leukemia rearrangements were found in 24 children, and 21 had undergone a stem cell transplant.

The children had a median of two prior lines of therapy, not including transplant. Seven of the children had received inotuzumab (Besponsa) and 11 had received blinotumumab (Blincyto).
 

High success rate

Of the 27 patients infused, 17 had sufficient cells harvested in a single day, and the remainder required 2-4 days. As noted, the CAR T product was successfully manufactured in 28 patients, with a median dose of 2.3 x 10⁶/kg of patient weight.

The treatment failed for 2 of the 26 efficacy-evaluable patients, resulting in an MRD-negative rate of 92%.

Event-free survival at 6 months was 67%, similar to that in ELIANA (73%), and the 12-month event-free survival was 58%, which was superior to that in ELIANA (50%).

The 6-month and 12-month overall survival rates among the younger children were identical at 88%, compared with 90% and 76%, respectively, in ELIANA.

The 6- and 12-month probability of ongoing B-cell depletion, indicating CAR T persistence, were 77% and 68%, respectively. In ELIANA, the 6-month probability of B-cell depletion was 83%.

A total of 10 of the 27 patients received further therapy, including 3 who were given maintenance therapy for poor CAR T persistence, 2 who underwent chemotherapy for relapse, and 5 who underwent allogeneic stem cell transplant.

Of six patients who experienced a relapse after having a complete response, two had CD19 relapse.
 

Low rate of serious CRS

At 30 days post infusion, grade 3 or greater cytokine release syndrome (CRS) had occurred in two patients, severe neurotoxicity occurred in one, and grade 3 or greater prolonged cytopenias occurred in eight patients.

The toxicity profile in this study was generally favorable in comparison with ELIANA, with shorter median duration of CRS, shorter median duration of CRS-related ICU stay, and a lower frequency of tocilizumab use. It should be noted, however, that the I-BFM investigators used American Society for Transplantation and Cellular Therapy CRS consenus criteria, whereas the ELIANA investigators used University of Pennsylvania criteria.

“If the longer-term follow-up data are encouraging, it might suggest that the outcomes from tisagenlecleucel therapy are comparable to that of stem cell transplantation in high-risk relapsed infant ALL, without the associated late effects, and possibly supports CAR T-cell therapy eventually replace stem cell transplantation in this setting,” Dr. Ghorashian said.

Dr. Curran, who leads the CAR T effort at MSK Kids, the children’s division of MSKCC, agreed that the goal is for CAR T to replace stem cell transplants.

“I hope I put my clinical practice out of business with my research practice,” he said, but added that “I think we need to do more research in figuring out how to best use CAR T cells, either earlier, or as some data suggest, by treating patients with lower disease burden we would get better durability.

“Because obviously in kids’ cancer one relapse is too much, and we want to be able to raise that bar and provide hope and a cure for all of our children,” he said.

The study was sponsored by the I-BFM Resistant Disease Committee and member institutions. Dr. Ghorashian disclosed advisory board activity for Novartis, maker of tisagenlecleucel, and patents and royalties from UCL Business. Dr. Curran research funding and consulting fees from Novartis.

Even the youngest patients with relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL) may be able to benefit from chimeric antigen reception T-cell (CAR T) therapy, investigators in an international consortium say.

Among 30 children aged under 2 years at the time of (B-ALL diagnosis, manufacturing of the CAR T product tisagenlecleucel (Kymriah) was feasible in 28 patients, and treatment resulted in high rates of minimal residual disease (MRD) negativity, complete responses, event-free survival, and overall survival, reported Sara Ghorashian, MD from the University College London Great Ormond Street Institute of Child Health, on behalf of the International BFM Resistant Disease Committee.

“The disease-related outcomes noted in this cohort of younger children predominantly with relapsed/refractory infant [mixed lineage leukemia]–rearranged ALL were at least as good as for the ELIANA study,” she said in an oral abstract presented during the European Hematology Association annual congress (Abstract S116).

The international, single-arm, open-label, ELIANA study was a phase 2 trial that included 97 patients aged 3-24 years with relapsed or refractory B-cell ALL, most of whom had previously undergone a hematopoietic stem cell transplant. Of those patients, 79 patients went on to receive a single infusion of the CAR T therapy.

“It’s fantastic data,” said Kevin J. Curran, MD, a pediatric hematologist/oncologist specializing in stem cell transplants and cellular therapy at Memorial Sloan Kettering Cancer Center, New York.

“Pediatric leukemia, while it’s the most common malignancy that happens in children, when you get down to this really small group, this under 3-year-old group, it’s hard to get a cohort, and for them to put together 30 patients, and show these great results is groundbreaking,” he said in an interview.

“Most importantly, it gives hope to parents who have young children who have really difficult to treat leukemia,” he said.

Dr. Curran was not involved in the study.
 

Scarce data on ALL in infants

“Children under 3 years of age were excluded from the ELIANA study, yet in terms of having often highly aggressive disease, with traditionally poor outcomes with conventional therapy, the need for novel forms of therapy for children with relapsed infant ALL is important,” Dr. Ghorashian said.

Because there is a paucity of data on outcomes in the youngest children, some health authorities will not support the use of tisagenlecleucel in this age group, and there are concerns about difficulties with performing leukapheresis in children weighing less than 10 kg, she noted.

To gain a better understanding of outcomes, members of the International BFM (Berlin-Frankfurt-Munster) Study Group conducted a retrospective analysis of data on all patients assessed for tisagenlecleucel for B-ALL who were aged under 3 years at screening at 1 of 15 centers in Europe and Israel.

A total of 30 patients were screened and had T cells harvested. Of this group, three patients did not receive CAR T infusions, two because of manufacturing failures, and one because of progressive disease.

Of the 27 patients who received CAR T infusions, 26 were evaluable for disease outcomes (1 had yet to reach the 30-day post infusion at the time of data cutoff).

The median age at diagnosis was 4.4 months, and the median age at infusion was 17.4 months; 19 of the 30 children in the entire cohort were boys. Mixed lineage leukemia rearrangements were found in 24 children, and 21 had undergone a stem cell transplant.

The children had a median of two prior lines of therapy, not including transplant. Seven of the children had received inotuzumab (Besponsa) and 11 had received blinotumumab (Blincyto).
 

High success rate

Of the 27 patients infused, 17 had sufficient cells harvested in a single day, and the remainder required 2-4 days. As noted, the CAR T product was successfully manufactured in 28 patients, with a median dose of 2.3 x 10⁶/kg of patient weight.

The treatment failed for 2 of the 26 efficacy-evaluable patients, resulting in an MRD-negative rate of 92%.

Event-free survival at 6 months was 67%, similar to that in ELIANA (73%), and the 12-month event-free survival was 58%, which was superior to that in ELIANA (50%).

The 6-month and 12-month overall survival rates among the younger children were identical at 88%, compared with 90% and 76%, respectively, in ELIANA.

The 6- and 12-month probability of ongoing B-cell depletion, indicating CAR T persistence, were 77% and 68%, respectively. In ELIANA, the 6-month probability of B-cell depletion was 83%.

A total of 10 of the 27 patients received further therapy, including 3 who were given maintenance therapy for poor CAR T persistence, 2 who underwent chemotherapy for relapse, and 5 who underwent allogeneic stem cell transplant.

Of six patients who experienced a relapse after having a complete response, two had CD19 relapse.
 

Low rate of serious CRS

At 30 days post infusion, grade 3 or greater cytokine release syndrome (CRS) had occurred in two patients, severe neurotoxicity occurred in one, and grade 3 or greater prolonged cytopenias occurred in eight patients.

The toxicity profile in this study was generally favorable in comparison with ELIANA, with shorter median duration of CRS, shorter median duration of CRS-related ICU stay, and a lower frequency of tocilizumab use. It should be noted, however, that the I-BFM investigators used American Society for Transplantation and Cellular Therapy CRS consenus criteria, whereas the ELIANA investigators used University of Pennsylvania criteria.

“If the longer-term follow-up data are encouraging, it might suggest that the outcomes from tisagenlecleucel therapy are comparable to that of stem cell transplantation in high-risk relapsed infant ALL, without the associated late effects, and possibly supports CAR T-cell therapy eventually replace stem cell transplantation in this setting,” Dr. Ghorashian said.

Dr. Curran, who leads the CAR T effort at MSK Kids, the children’s division of MSKCC, agreed that the goal is for CAR T to replace stem cell transplants.

“I hope I put my clinical practice out of business with my research practice,” he said, but added that “I think we need to do more research in figuring out how to best use CAR T cells, either earlier, or as some data suggest, by treating patients with lower disease burden we would get better durability.

“Because obviously in kids’ cancer one relapse is too much, and we want to be able to raise that bar and provide hope and a cure for all of our children,” he said.

The study was sponsored by the I-BFM Resistant Disease Committee and member institutions. Dr. Ghorashian disclosed advisory board activity for Novartis, maker of tisagenlecleucel, and patents and royalties from UCL Business. Dr. Curran research funding and consulting fees from Novartis.

Patients with obesity who had bariatric surgery had a lower risk of having a major adverse cardiovascular event (MACE) or dying from all causes during a median 7-year follow-up, compared with similar patients who did not undergo surgery.

These findings, from a province-wide retrospective cohort study from Quebec, follow two recent, slightly shorter similar trials.

Now we need a large randomized clinical trial (RCT), experts say, to definitively establish cardiovascular and mortality benefits in people with obesity who have metabolic/bariatric surgery. And such a trial is just beginning.

Philippe Bouchard, MD, a general surgery resident from McGill University in Montreal presented the Quebec study in a top papers session at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

The findings showed that, among obese patients with metabolic syndrome, bariatric/metabolic surgery is associated with a sustained decrease in the incidence of MACE and all-cause mortality of at least 5 years, Dr. Bouchard said.

“The results of this population-based observational study should be validated in randomized controlled trials,” he concluded.

In the meantime, “we believe our study adds to the body of evidence in mainly two ways,” Dr. Bouchard told this news organization in an email.

It has a longer follow-up than recent observational studies, “a median of 7 years, compared to 3.9 years in a study from the Cleveland Clinic, and 4.6 years in one from Ontario, he said.

“This allows us to [estimate] an absolute risk reduction of MACE of 5.11% at 10 years,” he added. This is a smaller risk reduction than the roughly 40% risk reduction seen in the other two studies, possibly because of selection bias, Dr. Bouchard speculated.

“Second, most of the larger cohorts are heavily weighted on Roux-en-Y gastric bypass,” he continued. In contrast, their study included diverse procedures, including sleeve gastrectomy, duodenal switch, and adjustable gastric banding.

“Given the rise in popularity of a derivative of the duodenal switch – the single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADi-S) – we believe this information is timely and relevant to clinicians,” Dr. Bouchard said.
 

RCT on the subject is coming

“I totally agree that we need a large randomized controlled trial of bariatric surgery versus optimal medical therapy to conclusively establish” the impact of bariatric surgery on cardiovascular outcomes, said the assigned discussant, Mehran Anvari, MD. And their research group is just about to begin one.

In the absence of RCT data, clinicians “may currently not refer [eligible] patients for bariatric surgery because of the high risk they pose,” said Dr. Anvari, professor and director of the Centre for Minimal Access Surgery of McMaster University, Hamilton, Ont., and senior author in the Ontario study.

Furthermore, an important point is that the current trial extended the follow-up to 7 years, he told this news organization in an email.

That study included patients with diabetes and hypertension, he added, whereas his group included patients with a history of cardiovascular disease and/or heart failure.

“We hope these studies encourage general practitioners and cardiologists to consider bariatric surgery as a viable treatment option to prevent and reduce the risk of MACE in the obese patients [body mass index >35 kg/m²] with significant cardiovascular disease,” he said.

“We have embarked on a pilot RCT among bariatric centers of excellence in Ontario,” Dr. Anvari added, which showed the feasibility and safety of such a study.

He estimates that the RCT will need to recruit 2,000 patients to demonstrate the safety and effectiveness of bariatric surgery in reducing MACE and cardiac and all-cause mortality among patients with existing cardiovascular disease.

This “will require international collaboration,” he added, “and our group is currently establishing collaboration with sites in North America, Europe, and Australia to conduct such a study.”
 

Patients matched for age, sex, number of comorbidities

Quebec has a single public health care system that covers the cost of bariatric surgery for eligible patients; that is, those with a BMI greater than 35 kg/m² and comorbidities or a BMI greater than 40 kg/m².

Using this provincial health care database, which covers over 97% of the population, the researchers identified 3,637 patients with diabetes and/or hypertension who had bariatric surgery during 2007-2012.

They matched the surgery patients with 5,420 control patients with obesity who lived in the same geographic region and had a similar age, sex, and number of Charlson Comorbidity Index comorbidities, but did not undergo bariatric surgery.

The patients had a mean age of 50 and 64% were women.

Half had zero to one comorbidities, a quarter had two comorbidities, and another quarter had at least three comorbidities.

Most patients in the surgery group had type 2 diabetes (70%) and 50% had hypertension, whereas in the control group, most patients had hypertension (82%) and 41% had diabetes.

The most common type of bariatric surgery was adjustable gastric banding (42% of patients), followed by duodenal switch (24%), sleeve gastrectomy (23%), and Roux-en-Y gastric bypass (11%).

The primary outcome was the incidence of MACE, defined as coronary artery events (including myocardial infarction, percutaneous coronary intervention, and coronary artery bypass graft), stroke, heart failure, and all-cause mortality,

After a median follow-up of 7-11 years, fewer patients in the surgical group than in the control group had MACE (20% vs. 25%) or died from all causes (4.1% vs. 6.3%, both statistically significant at P < .01)

Similarly, significantly fewer patients in the surgical group than in the control group had a coronary artery event or heart failure (each P < .01).

However, there were no significant between-group difference in the rate of stroke, possibly because of the small number of strokes.

The risk of MACE was 17% lower in the group that had bariatric surgery than in the control group (adjusted hazard ratio, 0.83; 95% confidence interval, 0.78-0.89), after adjusting for age, sex, and number of comorbidities.

In subgroup analysis, patients who had adjustable gastric banding, Roux-en-Y gastric bypass, or duodenal switch had a significantly lower risk of MACE than control patients.

The risk of MACE was similar in patients who had sleeve gastrectomy and in control patients.

However, these subgroup results need to be interpreted with caution since the surgery and control patients in each surgery type subgroup were not matched for age, sex, and comorbidities, said Dr. Bouchard.

He acknowledged that study limitations include a lack of information about the patients’ BMI, weight, medications, and glycemic control (hemoglobin A1c).

Dr. Bouchard and Dr. Anvari have no relevant financial disclosures.

Patients with obesity who had bariatric surgery had a lower risk of having a major adverse cardiovascular event (MACE) or dying from all causes during a median 7-year follow-up, compared with similar patients who did not undergo surgery.

These findings, from a province-wide retrospective cohort study from Quebec, follow two recent, slightly shorter similar trials.

Now we need a large randomized clinical trial (RCT), experts say, to definitively establish cardiovascular and mortality benefits in people with obesity who have metabolic/bariatric surgery. And such a trial is just beginning.

Philippe Bouchard, MD, a general surgery resident from McGill University in Montreal presented the Quebec study in a top papers session at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

The findings showed that, among obese patients with metabolic syndrome, bariatric/metabolic surgery is associated with a sustained decrease in the incidence of MACE and all-cause mortality of at least 5 years, Dr. Bouchard said.

“The results of this population-based observational study should be validated in randomized controlled trials,” he concluded.

In the meantime, “we believe our study adds to the body of evidence in mainly two ways,” Dr. Bouchard told this news organization in an email.

It has a longer follow-up than recent observational studies, “a median of 7 years, compared to 3.9 years in a study from the Cleveland Clinic, and 4.6 years in one from Ontario, he said.

“This allows us to [estimate] an absolute risk reduction of MACE of 5.11% at 10 years,” he added. This is a smaller risk reduction than the roughly 40% risk reduction seen in the other two studies, possibly because of selection bias, Dr. Bouchard speculated.

“Second, most of the larger cohorts are heavily weighted on Roux-en-Y gastric bypass,” he continued. In contrast, their study included diverse procedures, including sleeve gastrectomy, duodenal switch, and adjustable gastric banding.

“Given the rise in popularity of a derivative of the duodenal switch – the single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADi-S) – we believe this information is timely and relevant to clinicians,” Dr. Bouchard said.
 

RCT on the subject is coming

“I totally agree that we need a large randomized controlled trial of bariatric surgery versus optimal medical therapy to conclusively establish” the impact of bariatric surgery on cardiovascular outcomes, said the assigned discussant, Mehran Anvari, MD. And their research group is just about to begin one.

In the absence of RCT data, clinicians “may currently not refer [eligible] patients for bariatric surgery because of the high risk they pose,” said Dr. Anvari, professor and director of the Centre for Minimal Access Surgery of McMaster University, Hamilton, Ont., and senior author in the Ontario study.

Furthermore, an important point is that the current trial extended the follow-up to 7 years, he told this news organization in an email.

That study included patients with diabetes and hypertension, he added, whereas his group included patients with a history of cardiovascular disease and/or heart failure.

“We hope these studies encourage general practitioners and cardiologists to consider bariatric surgery as a viable treatment option to prevent and reduce the risk of MACE in the obese patients [body mass index >35 kg/m²] with significant cardiovascular disease,” he said.

“We have embarked on a pilot RCT among bariatric centers of excellence in Ontario,” Dr. Anvari added, which showed the feasibility and safety of such a study.

He estimates that the RCT will need to recruit 2,000 patients to demonstrate the safety and effectiveness of bariatric surgery in reducing MACE and cardiac and all-cause mortality among patients with existing cardiovascular disease.

This “will require international collaboration,” he added, “and our group is currently establishing collaboration with sites in North America, Europe, and Australia to conduct such a study.”
 

Patients matched for age, sex, number of comorbidities

Quebec has a single public health care system that covers the cost of bariatric surgery for eligible patients; that is, those with a BMI greater than 35 kg/m² and comorbidities or a BMI greater than 40 kg/m².

Using this provincial health care database, which covers over 97% of the population, the researchers identified 3,637 patients with diabetes and/or hypertension who had bariatric surgery during 2007-2012.

They matched the surgery patients with 5,420 control patients with obesity who lived in the same geographic region and had a similar age, sex, and number of Charlson Comorbidity Index comorbidities, but did not undergo bariatric surgery.

The patients had a mean age of 50 and 64% were women.

Half had zero to one comorbidities, a quarter had two comorbidities, and another quarter had at least three comorbidities.

Most patients in the surgery group had type 2 diabetes (70%) and 50% had hypertension, whereas in the control group, most patients had hypertension (82%) and 41% had diabetes.

The most common type of bariatric surgery was adjustable gastric banding (42% of patients), followed by duodenal switch (24%), sleeve gastrectomy (23%), and Roux-en-Y gastric bypass (11%).

The primary outcome was the incidence of MACE, defined as coronary artery events (including myocardial infarction, percutaneous coronary intervention, and coronary artery bypass graft), stroke, heart failure, and all-cause mortality,

After a median follow-up of 7-11 years, fewer patients in the surgical group than in the control group had MACE (20% vs. 25%) or died from all causes (4.1% vs. 6.3%, both statistically significant at P < .01)

Similarly, significantly fewer patients in the surgical group than in the control group had a coronary artery event or heart failure (each P < .01).

However, there were no significant between-group difference in the rate of stroke, possibly because of the small number of strokes.

The risk of MACE was 17% lower in the group that had bariatric surgery than in the control group (adjusted hazard ratio, 0.83; 95% confidence interval, 0.78-0.89), after adjusting for age, sex, and number of comorbidities.

In subgroup analysis, patients who had adjustable gastric banding, Roux-en-Y gastric bypass, or duodenal switch had a significantly lower risk of MACE than control patients.

The risk of MACE was similar in patients who had sleeve gastrectomy and in control patients.

However, these subgroup results need to be interpreted with caution since the surgery and control patients in each surgery type subgroup were not matched for age, sex, and comorbidities, said Dr. Bouchard.

He acknowledged that study limitations include a lack of information about the patients’ BMI, weight, medications, and glycemic control (hemoglobin A1c).

Dr. Bouchard and Dr. Anvari have no relevant financial disclosures.

Patients with obesity who had bariatric surgery had a lower risk of having a major adverse cardiovascular event (MACE) or dying from all causes during a median 7-year follow-up, compared with similar patients who did not undergo surgery.

These findings, from a province-wide retrospective cohort study from Quebec, follow two recent, slightly shorter similar trials.

Now we need a large randomized clinical trial (RCT), experts say, to definitively establish cardiovascular and mortality benefits in people with obesity who have metabolic/bariatric surgery. And such a trial is just beginning.

Philippe Bouchard, MD, a general surgery resident from McGill University in Montreal presented the Quebec study in a top papers session at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

The findings showed that, among obese patients with metabolic syndrome, bariatric/metabolic surgery is associated with a sustained decrease in the incidence of MACE and all-cause mortality of at least 5 years, Dr. Bouchard said.

“The results of this population-based observational study should be validated in randomized controlled trials,” he concluded.

In the meantime, “we believe our study adds to the body of evidence in mainly two ways,” Dr. Bouchard told this news organization in an email.

It has a longer follow-up than recent observational studies, “a median of 7 years, compared to 3.9 years in a study from the Cleveland Clinic, and 4.6 years in one from Ontario, he said.

“This allows us to [estimate] an absolute risk reduction of MACE of 5.11% at 10 years,” he added. This is a smaller risk reduction than the roughly 40% risk reduction seen in the other two studies, possibly because of selection bias, Dr. Bouchard speculated.

“Second, most of the larger cohorts are heavily weighted on Roux-en-Y gastric bypass,” he continued. In contrast, their study included diverse procedures, including sleeve gastrectomy, duodenal switch, and adjustable gastric banding.

“Given the rise in popularity of a derivative of the duodenal switch – the single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADi-S) – we believe this information is timely and relevant to clinicians,” Dr. Bouchard said.
 

RCT on the subject is coming

“I totally agree that we need a large randomized controlled trial of bariatric surgery versus optimal medical therapy to conclusively establish” the impact of bariatric surgery on cardiovascular outcomes, said the assigned discussant, Mehran Anvari, MD. And their research group is just about to begin one.

In the absence of RCT data, clinicians “may currently not refer [eligible] patients for bariatric surgery because of the high risk they pose,” said Dr. Anvari, professor and director of the Centre for Minimal Access Surgery of McMaster University, Hamilton, Ont., and senior author in the Ontario study.

Furthermore, an important point is that the current trial extended the follow-up to 7 years, he told this news organization in an email.

That study included patients with diabetes and hypertension, he added, whereas his group included patients with a history of cardiovascular disease and/or heart failure.

“We hope these studies encourage general practitioners and cardiologists to consider bariatric surgery as a viable treatment option to prevent and reduce the risk of MACE in the obese patients [body mass index >35 kg/m²] with significant cardiovascular disease,” he said.

“We have embarked on a pilot RCT among bariatric centers of excellence in Ontario,” Dr. Anvari added, which showed the feasibility and safety of such a study.

He estimates that the RCT will need to recruit 2,000 patients to demonstrate the safety and effectiveness of bariatric surgery in reducing MACE and cardiac and all-cause mortality among patients with existing cardiovascular disease.

This “will require international collaboration,” he added, “and our group is currently establishing collaboration with sites in North America, Europe, and Australia to conduct such a study.”
 

Patients matched for age, sex, number of comorbidities

Quebec has a single public health care system that covers the cost of bariatric surgery for eligible patients; that is, those with a BMI greater than 35 kg/m² and comorbidities or a BMI greater than 40 kg/m².

Using this provincial health care database, which covers over 97% of the population, the researchers identified 3,637 patients with diabetes and/or hypertension who had bariatric surgery during 2007-2012.

They matched the surgery patients with 5,420 control patients with obesity who lived in the same geographic region and had a similar age, sex, and number of Charlson Comorbidity Index comorbidities, but did not undergo bariatric surgery.

The patients had a mean age of 50 and 64% were women.

Half had zero to one comorbidities, a quarter had two comorbidities, and another quarter had at least three comorbidities.

Most patients in the surgery group had type 2 diabetes (70%) and 50% had hypertension, whereas in the control group, most patients had hypertension (82%) and 41% had diabetes.

The most common type of bariatric surgery was adjustable gastric banding (42% of patients), followed by duodenal switch (24%), sleeve gastrectomy (23%), and Roux-en-Y gastric bypass (11%).

The primary outcome was the incidence of MACE, defined as coronary artery events (including myocardial infarction, percutaneous coronary intervention, and coronary artery bypass graft), stroke, heart failure, and all-cause mortality,

After a median follow-up of 7-11 years, fewer patients in the surgical group than in the control group had MACE (20% vs. 25%) or died from all causes (4.1% vs. 6.3%, both statistically significant at P < .01)

Similarly, significantly fewer patients in the surgical group than in the control group had a coronary artery event or heart failure (each P < .01).

However, there were no significant between-group difference in the rate of stroke, possibly because of the small number of strokes.

The risk of MACE was 17% lower in the group that had bariatric surgery than in the control group (adjusted hazard ratio, 0.83; 95% confidence interval, 0.78-0.89), after adjusting for age, sex, and number of comorbidities.

In subgroup analysis, patients who had adjustable gastric banding, Roux-en-Y gastric bypass, or duodenal switch had a significantly lower risk of MACE than control patients.

The risk of MACE was similar in patients who had sleeve gastrectomy and in control patients.

However, these subgroup results need to be interpreted with caution since the surgery and control patients in each surgery type subgroup were not matched for age, sex, and comorbidities, said Dr. Bouchard.

He acknowledged that study limitations include a lack of information about the patients’ BMI, weight, medications, and glycemic control (hemoglobin A1c).

Dr. Bouchard and Dr. Anvari have no relevant financial disclosures.

A clinical prediction rule combining procalcitonin, absolute neutrophil count, and urinalysis effectively identified most febrile infants at low risk for serious bacterial infections, based on data from 702 individuals

The clinical prediction rule (CPR) described in 2019 in JAMA Pediatrics was developed by the Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN) to identify febrile infants at low risk for serious bacterial infections in order to reduce unnecessary procedures, antibiotics use, and hospitalization, according to April Clawson, MD, of Arkansas Children’s Hospital, Little Rock, and colleagues.

In a poster presented at the Pediatric Academic Societies annual meeting, the researchers conducted an external validation of the rule via a retrospective, observational study of febrile infants aged 60 days and younger who presented to an urban pediatric ED between October 2014 and June 2019. The study population included 702 infants with an average age of 36 days. Approximately 45% were female, and 60% were White. Fever was defined as 38° C or greater. Exclusion criteria were prematurity, receipt of antibiotics in the past 48 hours, presence of an indwelling medical device, and evidence of focal infection (not including otitis media); those who were critically ill at presentation or had a previous medical condition were excluded as well, the researchers said. A serious bacterial infection (SBI) was defined as a urinary tract infection (UTI), bacteremia, or bacterial meningitis.

Based on the CPR, a patient is considered low risk for an SBI if all the following criteria are met: normal urinalysis (defined as absence of leukocyte esterase, nitrite, and 5 or less white blood cells per high power field); an absolute neutrophil count of 4,090/mL or less; and procalcitonin of 1.71 ng/mL or less.

Overall, 62 infants (8.8%) were diagnosed with an SBI, similar to the 9.3% seen in the parent study of the CPR, Dr. Clawson said.

Of these, 42 had a UTI only (6%), 10 had bacteremia only (1.4%), and 1 had meningitis only (0.1%). Another five infants had UTI with bacteremia (0.7%), and four had bacteremia and meningitis (0.6%).

According to the CPR, 432 infants met criteria for low risk and 270 were considered high risk. A total of five infants who were classified as low risk had SBIs, including two with UTIs, two with bacteremia, and one with meningitis.

“The CPR derived and validated by Kupperman et al. had a decreased sensitivity for the patients in our study and missed some SBIs,” Dr. Clawson noted. “However, it had a strong negative predictive value, so it may still be a useful CPR.”

The sensitivity for the CPR in the parent study and the current study was 97.7 and 91.9, respectively; specificity was 60 and 66.7, respectively. The negative predictive values for the parent and current studies were 99.6 and 98.8, respectively, and the positive predictive values were 20.7 and 21.1.

The results support the potential of the CPR, but more external validation is needed, they said.
 

PECARN rule keeps it simple

“It has always been a challenge to identify infants with fever with serious bacterial infections when they are well-appearing,” Yashas Nathani, MD, of Oklahoma University, Oklahoma City, said in an interview. “The clinical prediction rule offers a simple, step-by-step approach for pediatricians and emergency medicine physicians to stratify infants in high or low risk categories for SBIs. However, as with everything, validation of protocols, guidelines and decision-making algorithms is extremely important, especially as more clinicians start to employ this CPR to their daily practice. This study objectively puts the CPR to the test and offers an independent external validation.

“Although this study had a lower sensitivity in identifying infants with SBI using the clinical prediction rule as compared to the original study, the robust validation of negative predictive value is extremely important and not surprising,” said Dr. Nathani. “The goal of this CPR is to identify infants with low-risk for SBI and the stated NPV helps clinicians in doing just that.”

Overall, “the clinical prediction rule is a fantastic resource for physicians to identify potentially sick infants with fever, especially the ones that appear well on initial evaluation,” said Dr. Nathani. However, “it is important to acknowledge that this is merely a guideline, and not an absolute rule. Clinicians also must remain cautious, as this rule does not incorporate the presence of viral pathogens as a factor.

“It is important to continue the scientific quest to refine our approach in identifying infants with serious bacterial infections when fever is the only presentation,” Dr. Nathani noted. “Additional research is needed to continue fine-tuning this CPR and the thresholds for procalcitonin and absolute neutrophil counts to improve the sensitivity and specificity.” Research also is needed to explore whether this CPR can be extended to incorporate viral testing, “as a large number of infants with fever have viral pathogens as the primary etiology,” he concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Nathani had no financial conflicts to disclose.

A clinical prediction rule combining procalcitonin, absolute neutrophil count, and urinalysis effectively identified most febrile infants at low risk for serious bacterial infections, based on data from 702 individuals

The clinical prediction rule (CPR) described in 2019 in JAMA Pediatrics was developed by the Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN) to identify febrile infants at low risk for serious bacterial infections in order to reduce unnecessary procedures, antibiotics use, and hospitalization, according to April Clawson, MD, of Arkansas Children’s Hospital, Little Rock, and colleagues.

In a poster presented at the Pediatric Academic Societies annual meeting, the researchers conducted an external validation of the rule via a retrospective, observational study of febrile infants aged 60 days and younger who presented to an urban pediatric ED between October 2014 and June 2019. The study population included 702 infants with an average age of 36 days. Approximately 45% were female, and 60% were White. Fever was defined as 38° C or greater. Exclusion criteria were prematurity, receipt of antibiotics in the past 48 hours, presence of an indwelling medical device, and evidence of focal infection (not including otitis media); those who were critically ill at presentation or had a previous medical condition were excluded as well, the researchers said. A serious bacterial infection (SBI) was defined as a urinary tract infection (UTI), bacteremia, or bacterial meningitis.

Based on the CPR, a patient is considered low risk for an SBI if all the following criteria are met: normal urinalysis (defined as absence of leukocyte esterase, nitrite, and 5 or less white blood cells per high power field); an absolute neutrophil count of 4,090/mL or less; and procalcitonin of 1.71 ng/mL or less.

Overall, 62 infants (8.8%) were diagnosed with an SBI, similar to the 9.3% seen in the parent study of the CPR, Dr. Clawson said.

Of these, 42 had a UTI only (6%), 10 had bacteremia only (1.4%), and 1 had meningitis only (0.1%). Another five infants had UTI with bacteremia (0.7%), and four had bacteremia and meningitis (0.6%).

According to the CPR, 432 infants met criteria for low risk and 270 were considered high risk. A total of five infants who were classified as low risk had SBIs, including two with UTIs, two with bacteremia, and one with meningitis.

“The CPR derived and validated by Kupperman et al. had a decreased sensitivity for the patients in our study and missed some SBIs,” Dr. Clawson noted. “However, it had a strong negative predictive value, so it may still be a useful CPR.”

The sensitivity for the CPR in the parent study and the current study was 97.7 and 91.9, respectively; specificity was 60 and 66.7, respectively. The negative predictive values for the parent and current studies were 99.6 and 98.8, respectively, and the positive predictive values were 20.7 and 21.1.

The results support the potential of the CPR, but more external validation is needed, they said.
 

PECARN rule keeps it simple

“It has always been a challenge to identify infants with fever with serious bacterial infections when they are well-appearing,” Yashas Nathani, MD, of Oklahoma University, Oklahoma City, said in an interview. “The clinical prediction rule offers a simple, step-by-step approach for pediatricians and emergency medicine physicians to stratify infants in high or low risk categories for SBIs. However, as with everything, validation of protocols, guidelines and decision-making algorithms is extremely important, especially as more clinicians start to employ this CPR to their daily practice. This study objectively puts the CPR to the test and offers an independent external validation.

“Although this study had a lower sensitivity in identifying infants with SBI using the clinical prediction rule as compared to the original study, the robust validation of negative predictive value is extremely important and not surprising,” said Dr. Nathani. “The goal of this CPR is to identify infants with low-risk for SBI and the stated NPV helps clinicians in doing just that.”

Overall, “the clinical prediction rule is a fantastic resource for physicians to identify potentially sick infants with fever, especially the ones that appear well on initial evaluation,” said Dr. Nathani. However, “it is important to acknowledge that this is merely a guideline, and not an absolute rule. Clinicians also must remain cautious, as this rule does not incorporate the presence of viral pathogens as a factor.

“It is important to continue the scientific quest to refine our approach in identifying infants with serious bacterial infections when fever is the only presentation,” Dr. Nathani noted. “Additional research is needed to continue fine-tuning this CPR and the thresholds for procalcitonin and absolute neutrophil counts to improve the sensitivity and specificity.” Research also is needed to explore whether this CPR can be extended to incorporate viral testing, “as a large number of infants with fever have viral pathogens as the primary etiology,” he concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Nathani had no financial conflicts to disclose.

A clinical prediction rule combining procalcitonin, absolute neutrophil count, and urinalysis effectively identified most febrile infants at low risk for serious bacterial infections, based on data from 702 individuals

The clinical prediction rule (CPR) described in 2019 in JAMA Pediatrics was developed by the Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN) to identify febrile infants at low risk for serious bacterial infections in order to reduce unnecessary procedures, antibiotics use, and hospitalization, according to April Clawson, MD, of Arkansas Children’s Hospital, Little Rock, and colleagues.

In a poster presented at the Pediatric Academic Societies annual meeting, the researchers conducted an external validation of the rule via a retrospective, observational study of febrile infants aged 60 days and younger who presented to an urban pediatric ED between October 2014 and June 2019. The study population included 702 infants with an average age of 36 days. Approximately 45% were female, and 60% were White. Fever was defined as 38° C or greater. Exclusion criteria were prematurity, receipt of antibiotics in the past 48 hours, presence of an indwelling medical device, and evidence of focal infection (not including otitis media); those who were critically ill at presentation or had a previous medical condition were excluded as well, the researchers said. A serious bacterial infection (SBI) was defined as a urinary tract infection (UTI), bacteremia, or bacterial meningitis.

Based on the CPR, a patient is considered low risk for an SBI if all the following criteria are met: normal urinalysis (defined as absence of leukocyte esterase, nitrite, and 5 or less white blood cells per high power field); an absolute neutrophil count of 4,090/mL or less; and procalcitonin of 1.71 ng/mL or less.

Overall, 62 infants (8.8%) were diagnosed with an SBI, similar to the 9.3% seen in the parent study of the CPR, Dr. Clawson said.

Of these, 42 had a UTI only (6%), 10 had bacteremia only (1.4%), and 1 had meningitis only (0.1%). Another five infants had UTI with bacteremia (0.7%), and four had bacteremia and meningitis (0.6%).

According to the CPR, 432 infants met criteria for low risk and 270 were considered high risk. A total of five infants who were classified as low risk had SBIs, including two with UTIs, two with bacteremia, and one with meningitis.

“The CPR derived and validated by Kupperman et al. had a decreased sensitivity for the patients in our study and missed some SBIs,” Dr. Clawson noted. “However, it had a strong negative predictive value, so it may still be a useful CPR.”

The sensitivity for the CPR in the parent study and the current study was 97.7 and 91.9, respectively; specificity was 60 and 66.7, respectively. The negative predictive values for the parent and current studies were 99.6 and 98.8, respectively, and the positive predictive values were 20.7 and 21.1.

The results support the potential of the CPR, but more external validation is needed, they said.
 

PECARN rule keeps it simple

“It has always been a challenge to identify infants with fever with serious bacterial infections when they are well-appearing,” Yashas Nathani, MD, of Oklahoma University, Oklahoma City, said in an interview. “The clinical prediction rule offers a simple, step-by-step approach for pediatricians and emergency medicine physicians to stratify infants in high or low risk categories for SBIs. However, as with everything, validation of protocols, guidelines and decision-making algorithms is extremely important, especially as more clinicians start to employ this CPR to their daily practice. This study objectively puts the CPR to the test and offers an independent external validation.

“Although this study had a lower sensitivity in identifying infants with SBI using the clinical prediction rule as compared to the original study, the robust validation of negative predictive value is extremely important and not surprising,” said Dr. Nathani. “The goal of this CPR is to identify infants with low-risk for SBI and the stated NPV helps clinicians in doing just that.”

Overall, “the clinical prediction rule is a fantastic resource for physicians to identify potentially sick infants with fever, especially the ones that appear well on initial evaluation,” said Dr. Nathani. However, “it is important to acknowledge that this is merely a guideline, and not an absolute rule. Clinicians also must remain cautious, as this rule does not incorporate the presence of viral pathogens as a factor.

“It is important to continue the scientific quest to refine our approach in identifying infants with serious bacterial infections when fever is the only presentation,” Dr. Nathani noted. “Additional research is needed to continue fine-tuning this CPR and the thresholds for procalcitonin and absolute neutrophil counts to improve the sensitivity and specificity.” Research also is needed to explore whether this CPR can be extended to incorporate viral testing, “as a large number of infants with fever have viral pathogens as the primary etiology,” he concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Nathani had no financial conflicts to disclose.

Current evidence does not support use of “excited delirium” or “excited delirium syndrome” as a medical diagnosis, the American Medical Association said June 14, and the term should not be used unless clear diagnostic criteria are validated.

The term is disproportionately applied to people of color, “for whom inappropriate and excessive pharmacotherapy continues to be the norm instead of behavioral deescalation,” the report by the AMA’s Council on Science and Public Health stated, and is therefore indicative of systemic racism.

That conclusion was one of many included in CSAPH Report 2, which was adopted June 14 at the special meeting of the AMA House of Delegates.

The AMA also opposes “use of sedative/hypnotic and dissociative agents, including ketamine, as a pharmacologic intervention for agitated individuals in the out-of-hospital setting, when done solely for a law enforcement purpose.”

Medications typically used for restraint include dissociative ketamine, benzodiazepine sedatives such as midazolam, and antipsychotic medications including olanzapine or haloperidol, alone or in combination.

Kenneth Certa, MD, from the American Psychiatric Association, speaking on behalf of the section council on psychiatry, said in a reference committee hearing: “We have been very concerned over the years with the development of the inexact diagnosis of ‘agitated delirium’ or ‘excited delirium,’ especially after having had a number of individuals, more than what’s reported in the press, die by the use of ketamine in the field for this inexact diagnosis.”

Tamaan Osbourne-Roberts, MD, a delegate and CSAPH member, said the diagnosis lacks scientific evidence and is “disproportionately applied to otherwise healthy Black men in their mid-30s and these men are most likely to die from resulting first-responder actions.”

Dr. Osbourne-Roberts testified that deescalation training should be more widely used and that crisis intervention team models in which behavioral health specialists are first deployed to respond to behavioral health emergencies should be more prevalent.

Andrew Rudawsky, MD, an assistant medical director of two emergency departments and delegate from Ohio, speaking as an individual, testified: “I can tell you from first-hand experience that ‘excited delirium’ is very real. These acutely ill, unstable patients have an emergency medical condition best cared for by an emergency medicine physician.”

The report recognizes that drugs used outside a hospital setting by nonphysicians come with significant risks, particularly for those with underlying conditions and in terms of drug–drug interactions.

“I completely agree that medicine should not be practiced by law enforcement,” Dr. Rudawsky said. “I’m gravely concerned by the legal ramifications of stating that this condition doesn’t exist.”

He said he is optimistic that the Diagnostic and Statistical Manual of Mental Disorders (DSM) will be updated to include “excited delirium.”

The report urges that medical and behavioral health specialists, instead of law enforcement, serve as first responders and decision-makers in medical and mental health emergencies in local communities.

Additionally, the report urges that “administration of any pharmacologic treatments in the out-of-hospital setting be done equitably, in an evidence-based, antiracist, and stigma-free way.”

The report calls on law enforcement and frontline emergency medical service personnel, who are a part of the “dual response” in emergency situations, to engage in training overseen by EMS medical directors. “The training should minimally include deescalation techniques and the appropriate use of pharmacologic intervention for agitated individuals in the out-of-hospital setting,” the report states.

 

Recommendation on oversight draws controversy

Several commenters were emergency physicians and medical directors who expressed concern that investigation of potential cases of inappropriate pharmacologic intervention would be overseen by nonphysicians.

The CSAPH authors write that independent investigators are appropriate, whereas those in emergency medicine say EMS medical directors should lead oversight.

Stephen Epstein, MD, chair of the section council on emergency medicine, speaking on behalf of the section council, had moved for referral of the portion of the report that deals with oversight of EMS.

“We’re concerned that recommendation 6, by calling for independent investigators, would put nonphysicians in the position of supervising the practice of medicine of a board-approved specialty. This would set an unfortunate precedent for our AMA,” he said.

Dr. Epstein also said the American College of Emergency Physicians will soon release a report on “excited delirium,” which will add key information for debating the issue.

He added that a new report on the safety of ketamine in out-of-hospital use was published just last week in the Annals of Emergency Medicine. The authors reviewed more than 11,000 cases of the pharmacologic intervention over the past 2 years.

“We believe this information may add substantively to the recommendation in this report,” Dr. Epstein said.

Recommendation 6 was referred to the AMA Board for a decision, but the rest of the report was overwhelmingly adopted.

Dr. Certa, Dr. Osbourne-Roberts, Dr. Rudawsky, and Dr. Epstein have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Current evidence does not support use of “excited delirium” or “excited delirium syndrome” as a medical diagnosis, the American Medical Association said June 14, and the term should not be used unless clear diagnostic criteria are validated.

The term is disproportionately applied to people of color, “for whom inappropriate and excessive pharmacotherapy continues to be the norm instead of behavioral deescalation,” the report by the AMA’s Council on Science and Public Health stated, and is therefore indicative of systemic racism.

That conclusion was one of many included in CSAPH Report 2, which was adopted June 14 at the special meeting of the AMA House of Delegates.

The AMA also opposes “use of sedative/hypnotic and dissociative agents, including ketamine, as a pharmacologic intervention for agitated individuals in the out-of-hospital setting, when done solely for a law enforcement purpose.”

Medications typically used for restraint include dissociative ketamine, benzodiazepine sedatives such as midazolam, and antipsychotic medications including olanzapine or haloperidol, alone or in combination.

Kenneth Certa, MD, from the American Psychiatric Association, speaking on behalf of the section council on psychiatry, said in a reference committee hearing: “We have been very concerned over the years with the development of the inexact diagnosis of ‘agitated delirium’ or ‘excited delirium,’ especially after having had a number of individuals, more than what’s reported in the press, die by the use of ketamine in the field for this inexact diagnosis.”

Tamaan Osbourne-Roberts, MD, a delegate and CSAPH member, said the diagnosis lacks scientific evidence and is “disproportionately applied to otherwise healthy Black men in their mid-30s and these men are most likely to die from resulting first-responder actions.”

Dr. Osbourne-Roberts testified that deescalation training should be more widely used and that crisis intervention team models in which behavioral health specialists are first deployed to respond to behavioral health emergencies should be more prevalent.

Andrew Rudawsky, MD, an assistant medical director of two emergency departments and delegate from Ohio, speaking as an individual, testified: “I can tell you from first-hand experience that ‘excited delirium’ is very real. These acutely ill, unstable patients have an emergency medical condition best cared for by an emergency medicine physician.”

The report recognizes that drugs used outside a hospital setting by nonphysicians come with significant risks, particularly for those with underlying conditions and in terms of drug–drug interactions.

“I completely agree that medicine should not be practiced by law enforcement,” Dr. Rudawsky said. “I’m gravely concerned by the legal ramifications of stating that this condition doesn’t exist.”

He said he is optimistic that the Diagnostic and Statistical Manual of Mental Disorders (DSM) will be updated to include “excited delirium.”

The report urges that medical and behavioral health specialists, instead of law enforcement, serve as first responders and decision-makers in medical and mental health emergencies in local communities.

Additionally, the report urges that “administration of any pharmacologic treatments in the out-of-hospital setting be done equitably, in an evidence-based, antiracist, and stigma-free way.”

The report calls on law enforcement and frontline emergency medical service personnel, who are a part of the “dual response” in emergency situations, to engage in training overseen by EMS medical directors. “The training should minimally include deescalation techniques and the appropriate use of pharmacologic intervention for agitated individuals in the out-of-hospital setting,” the report states.

 

Recommendation on oversight draws controversy

Several commenters were emergency physicians and medical directors who expressed concern that investigation of potential cases of inappropriate pharmacologic intervention would be overseen by nonphysicians.

The CSAPH authors write that independent investigators are appropriate, whereas those in emergency medicine say EMS medical directors should lead oversight.

Stephen Epstein, MD, chair of the section council on emergency medicine, speaking on behalf of the section council, had moved for referral of the portion of the report that deals with oversight of EMS.

“We’re concerned that recommendation 6, by calling for independent investigators, would put nonphysicians in the position of supervising the practice of medicine of a board-approved specialty. This would set an unfortunate precedent for our AMA,” he said.

Dr. Epstein also said the American College of Emergency Physicians will soon release a report on “excited delirium,” which will add key information for debating the issue.

He added that a new report on the safety of ketamine in out-of-hospital use was published just last week in the Annals of Emergency Medicine. The authors reviewed more than 11,000 cases of the pharmacologic intervention over the past 2 years.

“We believe this information may add substantively to the recommendation in this report,” Dr. Epstein said.

Recommendation 6 was referred to the AMA Board for a decision, but the rest of the report was overwhelmingly adopted.

Dr. Certa, Dr. Osbourne-Roberts, Dr. Rudawsky, and Dr. Epstein have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Current evidence does not support use of “excited delirium” or “excited delirium syndrome” as a medical diagnosis, the American Medical Association said June 14, and the term should not be used unless clear diagnostic criteria are validated.

The term is disproportionately applied to people of color, “for whom inappropriate and excessive pharmacotherapy continues to be the norm instead of behavioral deescalation,” the report by the AMA’s Council on Science and Public Health stated, and is therefore indicative of systemic racism.

That conclusion was one of many included in CSAPH Report 2, which was adopted June 14 at the special meeting of the AMA House of Delegates.

The AMA also opposes “use of sedative/hypnotic and dissociative agents, including ketamine, as a pharmacologic intervention for agitated individuals in the out-of-hospital setting, when done solely for a law enforcement purpose.”

Medications typically used for restraint include dissociative ketamine, benzodiazepine sedatives such as midazolam, and antipsychotic medications including olanzapine or haloperidol, alone or in combination.

Kenneth Certa, MD, from the American Psychiatric Association, speaking on behalf of the section council on psychiatry, said in a reference committee hearing: “We have been very concerned over the years with the development of the inexact diagnosis of ‘agitated delirium’ or ‘excited delirium,’ especially after having had a number of individuals, more than what’s reported in the press, die by the use of ketamine in the field for this inexact diagnosis.”

Tamaan Osbourne-Roberts, MD, a delegate and CSAPH member, said the diagnosis lacks scientific evidence and is “disproportionately applied to otherwise healthy Black men in their mid-30s and these men are most likely to die from resulting first-responder actions.”

Dr. Osbourne-Roberts testified that deescalation training should be more widely used and that crisis intervention team models in which behavioral health specialists are first deployed to respond to behavioral health emergencies should be more prevalent.

Andrew Rudawsky, MD, an assistant medical director of two emergency departments and delegate from Ohio, speaking as an individual, testified: “I can tell you from first-hand experience that ‘excited delirium’ is very real. These acutely ill, unstable patients have an emergency medical condition best cared for by an emergency medicine physician.”

The report recognizes that drugs used outside a hospital setting by nonphysicians come with significant risks, particularly for those with underlying conditions and in terms of drug–drug interactions.

“I completely agree that medicine should not be practiced by law enforcement,” Dr. Rudawsky said. “I’m gravely concerned by the legal ramifications of stating that this condition doesn’t exist.”

He said he is optimistic that the Diagnostic and Statistical Manual of Mental Disorders (DSM) will be updated to include “excited delirium.”

The report urges that medical and behavioral health specialists, instead of law enforcement, serve as first responders and decision-makers in medical and mental health emergencies in local communities.

Additionally, the report urges that “administration of any pharmacologic treatments in the out-of-hospital setting be done equitably, in an evidence-based, antiracist, and stigma-free way.”

The report calls on law enforcement and frontline emergency medical service personnel, who are a part of the “dual response” in emergency situations, to engage in training overseen by EMS medical directors. “The training should minimally include deescalation techniques and the appropriate use of pharmacologic intervention for agitated individuals in the out-of-hospital setting,” the report states.

 

Recommendation on oversight draws controversy

Several commenters were emergency physicians and medical directors who expressed concern that investigation of potential cases of inappropriate pharmacologic intervention would be overseen by nonphysicians.

The CSAPH authors write that independent investigators are appropriate, whereas those in emergency medicine say EMS medical directors should lead oversight.

Stephen Epstein, MD, chair of the section council on emergency medicine, speaking on behalf of the section council, had moved for referral of the portion of the report that deals with oversight of EMS.

“We’re concerned that recommendation 6, by calling for independent investigators, would put nonphysicians in the position of supervising the practice of medicine of a board-approved specialty. This would set an unfortunate precedent for our AMA,” he said.

Dr. Epstein also said the American College of Emergency Physicians will soon release a report on “excited delirium,” which will add key information for debating the issue.

He added that a new report on the safety of ketamine in out-of-hospital use was published just last week in the Annals of Emergency Medicine. The authors reviewed more than 11,000 cases of the pharmacologic intervention over the past 2 years.

“We believe this information may add substantively to the recommendation in this report,” Dr. Epstein said.

Recommendation 6 was referred to the AMA Board for a decision, but the rest of the report was overwhelmingly adopted.

Dr. Certa, Dr. Osbourne-Roberts, Dr. Rudawsky, and Dr. Epstein have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Inpatient care utilization for hidradenitis suppurativa (HS) was higher for Black and Hispanic patients, compared with White patients, in an analysis of the 2012-2017 National Inpatient Sample.

The differences occurred despite Black and Hispanic patients being younger at the time of admission than White patients, and may reflect increased disease severity and management challenges in these patients with skin of color, Nishadh Sutaria, BS, a medical student at Tufts University, Boston, said at the annual Skin of Color Society symposium. “They may also reflect social inequities in access to dermatologists, with racial and ethnic minorities using inpatient services in lieu of outpatient care.”

Mr. Sutaria and coinvestigators, led by Shawn Kwatra, MD, of Johns Hopkins University, Baltimore, identified 8,040 HS admissions for White patients, 16,490 Black patients, and 2,405 for Hispanic patients during the 5-year period.

Black and Hispanic patients were significantly younger than White patients, with a mean age of 38.1 years and 35 years, respectively, compared with 42 years for White patients (P < .001 in each case). Compared with White patients, Black patients had more procedures (2.03 vs. 1.84, P = .006), a longer length of stay (5.82 days vs. 4.97 days, P = .001), and higher cost of care ($46,119 vs. $39,862, P = .010). Compared with White patients, Hispanic patients had higher cost of care ($52,334 vs. $39,862, P = .004).

“In these models, Black patients stayed almost a full day longer and accrued a charge of $8,000 more than White patients, and Hispanic patients stayed about a half-day longer and accrued a charge of almost $15,000 more than White patients,” Mr. Sutaria said.

In a multilinear regression analysis adjusting for age, sex, and insurance type, Black race correlated with more procedures, higher length of stay, and higher cost of care, and Hispanic ethnicity with more procedures and higher cost of care.

Prior research has shown that Black patients may be disproportionately affected by HS. A 2017 analysis of electronic health record data for tens of millions of patients nationally, for instance, showed an incidence of HS that was over 2.5 times greater in Blacks than Whites. And a recent analysis of electronic data in Wisconsin for patients with an HS diagnosis and 3 or more encounters for the disease showed that Blacks are more likely to have HS that is Hurley Stage 3, the most severe type.

Increased severity “has not been explicitly shown in Hispanic patients,” Dr. Kwatra said in an interview, “[but] there is a strong relationship between obesity/metabolic syndrome with HS. Because Hispanic patients have higher rates of obesity and metabolic syndrome, it’s [thought] that they may have more severe HS.”

HS patients with skin of color are underrepresented in clinical trials, he said. “Severe HS can be difficult to treat because there are few effective treatments,” he said, noting that adalimumab is the only Food and Drug Administration–approved therapy.

The National Inpatient Sample is a publicly available, all-payer inpatient care database developed for the Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project.

Mr. Sutaria is a dermatology research fellow working under the guidance of Dr. Kwatra.

Inpatient care utilization for hidradenitis suppurativa (HS) was higher for Black and Hispanic patients, compared with White patients, in an analysis of the 2012-2017 National Inpatient Sample.

The differences occurred despite Black and Hispanic patients being younger at the time of admission than White patients, and may reflect increased disease severity and management challenges in these patients with skin of color, Nishadh Sutaria, BS, a medical student at Tufts University, Boston, said at the annual Skin of Color Society symposium. “They may also reflect social inequities in access to dermatologists, with racial and ethnic minorities using inpatient services in lieu of outpatient care.”

Mr. Sutaria and coinvestigators, led by Shawn Kwatra, MD, of Johns Hopkins University, Baltimore, identified 8,040 HS admissions for White patients, 16,490 Black patients, and 2,405 for Hispanic patients during the 5-year period.

Black and Hispanic patients were significantly younger than White patients, with a mean age of 38.1 years and 35 years, respectively, compared with 42 years for White patients (P < .001 in each case). Compared with White patients, Black patients had more procedures (2.03 vs. 1.84, P = .006), a longer length of stay (5.82 days vs. 4.97 days, P = .001), and higher cost of care ($46,119 vs. $39,862, P = .010). Compared with White patients, Hispanic patients had higher cost of care ($52,334 vs. $39,862, P = .004).

“In these models, Black patients stayed almost a full day longer and accrued a charge of $8,000 more than White patients, and Hispanic patients stayed about a half-day longer and accrued a charge of almost $15,000 more than White patients,” Mr. Sutaria said.

In a multilinear regression analysis adjusting for age, sex, and insurance type, Black race correlated with more procedures, higher length of stay, and higher cost of care, and Hispanic ethnicity with more procedures and higher cost of care.

Prior research has shown that Black patients may be disproportionately affected by HS. A 2017 analysis of electronic health record data for tens of millions of patients nationally, for instance, showed an incidence of HS that was over 2.5 times greater in Blacks than Whites. And a recent analysis of electronic data in Wisconsin for patients with an HS diagnosis and 3 or more encounters for the disease showed that Blacks are more likely to have HS that is Hurley Stage 3, the most severe type.

Increased severity “has not been explicitly shown in Hispanic patients,” Dr. Kwatra said in an interview, “[but] there is a strong relationship between obesity/metabolic syndrome with HS. Because Hispanic patients have higher rates of obesity and metabolic syndrome, it’s [thought] that they may have more severe HS.”

HS patients with skin of color are underrepresented in clinical trials, he said. “Severe HS can be difficult to treat because there are few effective treatments,” he said, noting that adalimumab is the only Food and Drug Administration–approved therapy.

The National Inpatient Sample is a publicly available, all-payer inpatient care database developed for the Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project.

Mr. Sutaria is a dermatology research fellow working under the guidance of Dr. Kwatra.

Inpatient care utilization for hidradenitis suppurativa (HS) was higher for Black and Hispanic patients, compared with White patients, in an analysis of the 2012-2017 National Inpatient Sample.

The differences occurred despite Black and Hispanic patients being younger at the time of admission than White patients, and may reflect increased disease severity and management challenges in these patients with skin of color, Nishadh Sutaria, BS, a medical student at Tufts University, Boston, said at the annual Skin of Color Society symposium. “They may also reflect social inequities in access to dermatologists, with racial and ethnic minorities using inpatient services in lieu of outpatient care.”

Mr. Sutaria and coinvestigators, led by Shawn Kwatra, MD, of Johns Hopkins University, Baltimore, identified 8,040 HS admissions for White patients, 16,490 Black patients, and 2,405 for Hispanic patients during the 5-year period.

Black and Hispanic patients were significantly younger than White patients, with a mean age of 38.1 years and 35 years, respectively, compared with 42 years for White patients (P < .001 in each case). Compared with White patients, Black patients had more procedures (2.03 vs. 1.84, P = .006), a longer length of stay (5.82 days vs. 4.97 days, P = .001), and higher cost of care ($46,119 vs. $39,862, P = .010). Compared with White patients, Hispanic patients had higher cost of care ($52,334 vs. $39,862, P = .004).

“In these models, Black patients stayed almost a full day longer and accrued a charge of $8,000 more than White patients, and Hispanic patients stayed about a half-day longer and accrued a charge of almost $15,000 more than White patients,” Mr. Sutaria said.

In a multilinear regression analysis adjusting for age, sex, and insurance type, Black race correlated with more procedures, higher length of stay, and higher cost of care, and Hispanic ethnicity with more procedures and higher cost of care.

Prior research has shown that Black patients may be disproportionately affected by HS. A 2017 analysis of electronic health record data for tens of millions of patients nationally, for instance, showed an incidence of HS that was over 2.5 times greater in Blacks than Whites. And a recent analysis of electronic data in Wisconsin for patients with an HS diagnosis and 3 or more encounters for the disease showed that Blacks are more likely to have HS that is Hurley Stage 3, the most severe type.

Increased severity “has not been explicitly shown in Hispanic patients,” Dr. Kwatra said in an interview, “[but] there is a strong relationship between obesity/metabolic syndrome with HS. Because Hispanic patients have higher rates of obesity and metabolic syndrome, it’s [thought] that they may have more severe HS.”

HS patients with skin of color are underrepresented in clinical trials, he said. “Severe HS can be difficult to treat because there are few effective treatments,” he said, noting that adalimumab is the only Food and Drug Administration–approved therapy.

The National Inpatient Sample is a publicly available, all-payer inpatient care database developed for the Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project.

Mr. Sutaria is a dermatology research fellow working under the guidance of Dr. Kwatra.

The results from three small studies of targeted therapy for rare brain tumors were “remarkable,” according to Jaishri Blakeley, MD, a neurology professor at Johns Hopkins Medicine, Baltimore, who discussed the studies after they were presented at the American Society of Clinical Oncology meeting.

Although most patients don’t have targetable mutations, molecular testing “is well worth the effort,” for those that do. “I think it’s fair to say that precision medicine” – well established in other tumor types – “is finally here in full force for neuro-oncology,” Dr. Blakeley said.
 

A promising start

Fifteen of 16 patients (94%) in one study had newly diagnosed and untreated papillary craniopharyngiomas (PCPs) that harbored BRAF V600E mutations, a common finding in PCPs, which have no effective medical treatment.

Tumors shrunk 68%-99% in 14 patients (93%) after treatment with the BRAF inhibitor vemurafenib plus the MEK inhibitor cobimetinib, which was included to stave off resistance to vemurafenib. The 24-month progression free survival was 93%.

The combination resulted in significant response in all patients who received at least one cycle of therapy, with a median 91% volume reduction. “Our study indicates that BRAF/MEK inhibitors could be a powerful tool in the treatment of previously untreated PCP, with the potential to avoid the morbidity associated with radiation and surgery,” concluded lead investigator and presenter Priscilla K. Brastianos, MD, associate professor of medicine at Mass General Cancer Center, Boston.

Thirty-three people in the second study had a mix of high and low grade gliomas or other CNS tumors positive for TRK gene fusions, a known oncogenic driver; the majority were children. They were treated with the TRK inhibitor larotrectinib after progressing on other systemic therapies.

The objective response rate was 30%, and the disease control rate was 73% at 24 weeks, with a median time to best response of 1.9 months. Tumors shrank in 82% of evaluable patients. Median progression-free survival was 18.3 months, and overall survival was not reached.

“These results support testing for TRK gene fusions for all patients with CNS tumors, especially if there is no known driver and especially in infants,” concluded lead investigator and presenter Sebastien Perreault, MD, a clinical assistant neurosciences professor at the University of Montreal.

The third study tested ALK inhibitors such as crizotinib in seven patients with adult-onset neuroblastoma, a rare and almost invariably fatal tumor known to be enriched for ALK mutations; the subjects were positive for them.

Their disease remained stable anywhere from 3.4 to 37.4 months. Median time to progression was 15.5 months, and median overall survival was 46.5 months.

ALK inhibitors “can be a well-tolerated options for treatment, improving time to progression. Development of resistance to one agent does not preclude use of other agents in the same drug class. ALK inhibitors should be considered when treating patients with this diagnosis,” said lead investigator and presenter Jessica Stiefel, MD, a pediatric hematology oncology fellow at Memorial Sloan Kettering Cancer Center, New York.
 

A ‘strong’ recommendation

The data “are great news” across the board. Targeted therapy applied to the right CNS tumor can have “dramatic” benefit for tumor control, Dr. Blakeley said.

But organizing molecular testing is not straightforward and requires strategies to balance “the use of precious resources, such as time money, and tissue,” with the potential benefit. Interpretation of testing results isn’t straightforward either, and is best handled by a molecular tumor board. Clinical pharmacists are also key to accessing expensive medications off label for CNS tumors.

Adverse events are also a consideration. Most of the subjects in the PCP study had grade 3/4 toxicity. Three patients in the ALK inhibitor study had to stop because of adverse events. Almost 40% on larotrectinib had grade 3 or 4 toxicity; nobody came off treatment, but a third had to skip doses.

Once an actionable mutation is identified, Dr. Blakeley’s “strong recommendation” is to enroll patients in a clinical trial that targets it, to take advantage the structure already in place to secure treatment, managed patients, and assess outcomes.

The National Cancer Institute’s MATCH trial is one of several options.

The BRAF/MEK inhibitor study was funded by Genentech and the National Institutes of Health. Dr. Brastianos had ties to numerous companies, including Pfizer, Lilly, and Merck. The TRK inhibitor study was funded by Bayer/Lilly. Dr. Perreault is a speaker and researcher for the company and has other ties. Dr. Blakeley is an adviser and/or researcher for a number of companies, including AbbVie, Astellas, BMS, and Exelixis. Dr. Stiefel didn’t have any disclosures, and didn’t report outside funding.

aotto@mdedge.com

The results from three small studies of targeted therapy for rare brain tumors were “remarkable,” according to Jaishri Blakeley, MD, a neurology professor at Johns Hopkins Medicine, Baltimore, who discussed the studies after they were presented at the American Society of Clinical Oncology meeting.

Although most patients don’t have targetable mutations, molecular testing “is well worth the effort,” for those that do. “I think it’s fair to say that precision medicine” – well established in other tumor types – “is finally here in full force for neuro-oncology,” Dr. Blakeley said.
 

A promising start

Fifteen of 16 patients (94%) in one study had newly diagnosed and untreated papillary craniopharyngiomas (PCPs) that harbored BRAF V600E mutations, a common finding in PCPs, which have no effective medical treatment.

Tumors shrunk 68%-99% in 14 patients (93%) after treatment with the BRAF inhibitor vemurafenib plus the MEK inhibitor cobimetinib, which was included to stave off resistance to vemurafenib. The 24-month progression free survival was 93%.

The combination resulted in significant response in all patients who received at least one cycle of therapy, with a median 91% volume reduction. “Our study indicates that BRAF/MEK inhibitors could be a powerful tool in the treatment of previously untreated PCP, with the potential to avoid the morbidity associated with radiation and surgery,” concluded lead investigator and presenter Priscilla K. Brastianos, MD, associate professor of medicine at Mass General Cancer Center, Boston.

Thirty-three people in the second study had a mix of high and low grade gliomas or other CNS tumors positive for TRK gene fusions, a known oncogenic driver; the majority were children. They were treated with the TRK inhibitor larotrectinib after progressing on other systemic therapies.

The objective response rate was 30%, and the disease control rate was 73% at 24 weeks, with a median time to best response of 1.9 months. Tumors shrank in 82% of evaluable patients. Median progression-free survival was 18.3 months, and overall survival was not reached.

“These results support testing for TRK gene fusions for all patients with CNS tumors, especially if there is no known driver and especially in infants,” concluded lead investigator and presenter Sebastien Perreault, MD, a clinical assistant neurosciences professor at the University of Montreal.

The third study tested ALK inhibitors such as crizotinib in seven patients with adult-onset neuroblastoma, a rare and almost invariably fatal tumor known to be enriched for ALK mutations; the subjects were positive for them.

Their disease remained stable anywhere from 3.4 to 37.4 months. Median time to progression was 15.5 months, and median overall survival was 46.5 months.

ALK inhibitors “can be a well-tolerated options for treatment, improving time to progression. Development of resistance to one agent does not preclude use of other agents in the same drug class. ALK inhibitors should be considered when treating patients with this diagnosis,” said lead investigator and presenter Jessica Stiefel, MD, a pediatric hematology oncology fellow at Memorial Sloan Kettering Cancer Center, New York.
 

A ‘strong’ recommendation

The data “are great news” across the board. Targeted therapy applied to the right CNS tumor can have “dramatic” benefit for tumor control, Dr. Blakeley said.

But organizing molecular testing is not straightforward and requires strategies to balance “the use of precious resources, such as time money, and tissue,” with the potential benefit. Interpretation of testing results isn’t straightforward either, and is best handled by a molecular tumor board. Clinical pharmacists are also key to accessing expensive medications off label for CNS tumors.

Adverse events are also a consideration. Most of the subjects in the PCP study had grade 3/4 toxicity. Three patients in the ALK inhibitor study had to stop because of adverse events. Almost 40% on larotrectinib had grade 3 or 4 toxicity; nobody came off treatment, but a third had to skip doses.

Once an actionable mutation is identified, Dr. Blakeley’s “strong recommendation” is to enroll patients in a clinical trial that targets it, to take advantage the structure already in place to secure treatment, managed patients, and assess outcomes.

The National Cancer Institute’s MATCH trial is one of several options.

The BRAF/MEK inhibitor study was funded by Genentech and the National Institutes of Health. Dr. Brastianos had ties to numerous companies, including Pfizer, Lilly, and Merck. The TRK inhibitor study was funded by Bayer/Lilly. Dr. Perreault is a speaker and researcher for the company and has other ties. Dr. Blakeley is an adviser and/or researcher for a number of companies, including AbbVie, Astellas, BMS, and Exelixis. Dr. Stiefel didn’t have any disclosures, and didn’t report outside funding.

aotto@mdedge.com

The results from three small studies of targeted therapy for rare brain tumors were “remarkable,” according to Jaishri Blakeley, MD, a neurology professor at Johns Hopkins Medicine, Baltimore, who discussed the studies after they were presented at the American Society of Clinical Oncology meeting.

Although most patients don’t have targetable mutations, molecular testing “is well worth the effort,” for those that do. “I think it’s fair to say that precision medicine” – well established in other tumor types – “is finally here in full force for neuro-oncology,” Dr. Blakeley said.
 

A promising start

Fifteen of 16 patients (94%) in one study had newly diagnosed and untreated papillary craniopharyngiomas (PCPs) that harbored BRAF V600E mutations, a common finding in PCPs, which have no effective medical treatment.

Tumors shrunk 68%-99% in 14 patients (93%) after treatment with the BRAF inhibitor vemurafenib plus the MEK inhibitor cobimetinib, which was included to stave off resistance to vemurafenib. The 24-month progression free survival was 93%.

The combination resulted in significant response in all patients who received at least one cycle of therapy, with a median 91% volume reduction. “Our study indicates that BRAF/MEK inhibitors could be a powerful tool in the treatment of previously untreated PCP, with the potential to avoid the morbidity associated with radiation and surgery,” concluded lead investigator and presenter Priscilla K. Brastianos, MD, associate professor of medicine at Mass General Cancer Center, Boston.

Thirty-three people in the second study had a mix of high and low grade gliomas or other CNS tumors positive for TRK gene fusions, a known oncogenic driver; the majority were children. They were treated with the TRK inhibitor larotrectinib after progressing on other systemic therapies.

The objective response rate was 30%, and the disease control rate was 73% at 24 weeks, with a median time to best response of 1.9 months. Tumors shrank in 82% of evaluable patients. Median progression-free survival was 18.3 months, and overall survival was not reached.

“These results support testing for TRK gene fusions for all patients with CNS tumors, especially if there is no known driver and especially in infants,” concluded lead investigator and presenter Sebastien Perreault, MD, a clinical assistant neurosciences professor at the University of Montreal.

The third study tested ALK inhibitors such as crizotinib in seven patients with adult-onset neuroblastoma, a rare and almost invariably fatal tumor known to be enriched for ALK mutations; the subjects were positive for them.

Their disease remained stable anywhere from 3.4 to 37.4 months. Median time to progression was 15.5 months, and median overall survival was 46.5 months.

ALK inhibitors “can be a well-tolerated options for treatment, improving time to progression. Development of resistance to one agent does not preclude use of other agents in the same drug class. ALK inhibitors should be considered when treating patients with this diagnosis,” said lead investigator and presenter Jessica Stiefel, MD, a pediatric hematology oncology fellow at Memorial Sloan Kettering Cancer Center, New York.
 

A ‘strong’ recommendation

The data “are great news” across the board. Targeted therapy applied to the right CNS tumor can have “dramatic” benefit for tumor control, Dr. Blakeley said.

But organizing molecular testing is not straightforward and requires strategies to balance “the use of precious resources, such as time money, and tissue,” with the potential benefit. Interpretation of testing results isn’t straightforward either, and is best handled by a molecular tumor board. Clinical pharmacists are also key to accessing expensive medications off label for CNS tumors.

Adverse events are also a consideration. Most of the subjects in the PCP study had grade 3/4 toxicity. Three patients in the ALK inhibitor study had to stop because of adverse events. Almost 40% on larotrectinib had grade 3 or 4 toxicity; nobody came off treatment, but a third had to skip doses.

Once an actionable mutation is identified, Dr. Blakeley’s “strong recommendation” is to enroll patients in a clinical trial that targets it, to take advantage the structure already in place to secure treatment, managed patients, and assess outcomes.

The National Cancer Institute’s MATCH trial is one of several options.

The BRAF/MEK inhibitor study was funded by Genentech and the National Institutes of Health. Dr. Brastianos had ties to numerous companies, including Pfizer, Lilly, and Merck. The TRK inhibitor study was funded by Bayer/Lilly. Dr. Perreault is a speaker and researcher for the company and has other ties. Dr. Blakeley is an adviser and/or researcher for a number of companies, including AbbVie, Astellas, BMS, and Exelixis. Dr. Stiefel didn’t have any disclosures, and didn’t report outside funding.

aotto@mdedge.com