Given the age of the patient and the results of imaging, histology, and immunohistochemistry, the diagnosis is mucinous (colloid) carcinoma. The patient and oncologist discuss prognosis and discuss treatment options, such as breast-conserving surgery, local radiation, and possible adjuvant endocrine therapy.

Mucinous (colloid) carcinoma is a rare histologic subtype of invasive breast cancer that occurs in < 5% of patients and generally develops in those who are ≥ 60 years old. Patients with mucinous (colloid) carcinoma generally present with a palpable mass or, on imaging, a poorly defined tumor with rare calcifications. The histologic hallmark of mucinous (colloid) carcinoma is mucin production. There are two subtypes of mucinous breast carcinoma: pure and mixed. A pure mucinous tumor is defined as a carcinoma consisting of ≥ 90% intracellular or extracellular mucin. This pure subtype occurs more frequently than mixed mucinous breast carcinoma and is also less likely to metastasize to the lymph nodes.

Differential diagnosis can be challenging because mucinous (colloid) carcinoma can mimic a benign tumor on imaging, which is why it is important to include multiple factors when diagnosing in daily practice. According to the National Comprehensive Cancer Network (NCCN), diagnosing nonmetastatic invasive breast cancer like mucinous (colloid) carcinoma involves patient history and physical exam, diagnostic bilateral mammography (ultrasound and breast MRI, as needed), pathology review, tumor estrogen/progesterone receptor status, HER2 status, and genetic counseling for those with a family history. In most cases of mucinous (colloid) carcinoma, tumors are ER- and PR-positive and HER2-negative. 

A pure mucinous histologic subtype is generally associated with a favorable prognosis; 10-year survival rates of mucinous (colloid) carcinoma are > 80%. The tumor is generally not high grade and is most often classified on surgical excision. Two main types of lesions exist — A and B — as does a combination of AB. Type A has larger quantities of extracellular mucin and is considered the classic form of mucinous carcinoma. Type B is a distinct variant with endocrine differentiation. In addition, glycoproteins MUC2 and MUC6 are predominantly expressed in mucinous (colloid) carcinoma; ductal carcinoma in situ is not often found in this setting. 

NCCN recommends multidisciplinary care and development of a personalized survivorship treatment plan, which includes a customized summary of possible long-term treatment toxicities. In addition, multidisciplinary care coordination encourages close follow-up that helps patients adhere to their medications and stay current with ongoing screening.

Breast-conserving surgery and local radiation therapy are often the two modalities used to treat mucinous (colloid) carcinoma, especially because prognosis is so favorable. NCCN recommends the consideration of adjuvant endocrine treatment for patients with pure mucinous tumors that are HER2-negative and ER-positive and/or PR-positive; staged at pT1, pT2, or pT3, and pN0 or pN1mi; and ≤ 2.9 cm. Adjuvant endocrine therapy is recommended for patients with the same disease characteristics whose tumor is ≥ 3 cm.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Given the age of the patient and the results of imaging, histology, and immunohistochemistry, the diagnosis is mucinous (colloid) carcinoma. The patient and oncologist discuss prognosis and discuss treatment options, such as breast-conserving surgery, local radiation, and possible adjuvant endocrine therapy.

Mucinous (colloid) carcinoma is a rare histologic subtype of invasive breast cancer that occurs in < 5% of patients and generally develops in those who are ≥ 60 years old. Patients with mucinous (colloid) carcinoma generally present with a palpable mass or, on imaging, a poorly defined tumor with rare calcifications. The histologic hallmark of mucinous (colloid) carcinoma is mucin production. There are two subtypes of mucinous breast carcinoma: pure and mixed. A pure mucinous tumor is defined as a carcinoma consisting of ≥ 90% intracellular or extracellular mucin. This pure subtype occurs more frequently than mixed mucinous breast carcinoma and is also less likely to metastasize to the lymph nodes.

Differential diagnosis can be challenging because mucinous (colloid) carcinoma can mimic a benign tumor on imaging, which is why it is important to include multiple factors when diagnosing in daily practice. According to the National Comprehensive Cancer Network (NCCN), diagnosing nonmetastatic invasive breast cancer like mucinous (colloid) carcinoma involves patient history and physical exam, diagnostic bilateral mammography (ultrasound and breast MRI, as needed), pathology review, tumor estrogen/progesterone receptor status, HER2 status, and genetic counseling for those with a family history. In most cases of mucinous (colloid) carcinoma, tumors are ER- and PR-positive and HER2-negative. 

A pure mucinous histologic subtype is generally associated with a favorable prognosis; 10-year survival rates of mucinous (colloid) carcinoma are > 80%. The tumor is generally not high grade and is most often classified on surgical excision. Two main types of lesions exist — A and B — as does a combination of AB. Type A has larger quantities of extracellular mucin and is considered the classic form of mucinous carcinoma. Type B is a distinct variant with endocrine differentiation. In addition, glycoproteins MUC2 and MUC6 are predominantly expressed in mucinous (colloid) carcinoma; ductal carcinoma in situ is not often found in this setting. 

NCCN recommends multidisciplinary care and development of a personalized survivorship treatment plan, which includes a customized summary of possible long-term treatment toxicities. In addition, multidisciplinary care coordination encourages close follow-up that helps patients adhere to their medications and stay current with ongoing screening.

Breast-conserving surgery and local radiation therapy are often the two modalities used to treat mucinous (colloid) carcinoma, especially because prognosis is so favorable. NCCN recommends the consideration of adjuvant endocrine treatment for patients with pure mucinous tumors that are HER2-negative and ER-positive and/or PR-positive; staged at pT1, pT2, or pT3, and pN0 or pN1mi; and ≤ 2.9 cm. Adjuvant endocrine therapy is recommended for patients with the same disease characteristics whose tumor is ≥ 3 cm.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Given the age of the patient and the results of imaging, histology, and immunohistochemistry, the diagnosis is mucinous (colloid) carcinoma. The patient and oncologist discuss prognosis and discuss treatment options, such as breast-conserving surgery, local radiation, and possible adjuvant endocrine therapy.

Mucinous (colloid) carcinoma is a rare histologic subtype of invasive breast cancer that occurs in < 5% of patients and generally develops in those who are ≥ 60 years old. Patients with mucinous (colloid) carcinoma generally present with a palpable mass or, on imaging, a poorly defined tumor with rare calcifications. The histologic hallmark of mucinous (colloid) carcinoma is mucin production. There are two subtypes of mucinous breast carcinoma: pure and mixed. A pure mucinous tumor is defined as a carcinoma consisting of ≥ 90% intracellular or extracellular mucin. This pure subtype occurs more frequently than mixed mucinous breast carcinoma and is also less likely to metastasize to the lymph nodes.

Differential diagnosis can be challenging because mucinous (colloid) carcinoma can mimic a benign tumor on imaging, which is why it is important to include multiple factors when diagnosing in daily practice. According to the National Comprehensive Cancer Network (NCCN), diagnosing nonmetastatic invasive breast cancer like mucinous (colloid) carcinoma involves patient history and physical exam, diagnostic bilateral mammography (ultrasound and breast MRI, as needed), pathology review, tumor estrogen/progesterone receptor status, HER2 status, and genetic counseling for those with a family history. In most cases of mucinous (colloid) carcinoma, tumors are ER- and PR-positive and HER2-negative. 

A pure mucinous histologic subtype is generally associated with a favorable prognosis; 10-year survival rates of mucinous (colloid) carcinoma are > 80%. The tumor is generally not high grade and is most often classified on surgical excision. Two main types of lesions exist — A and B — as does a combination of AB. Type A has larger quantities of extracellular mucin and is considered the classic form of mucinous carcinoma. Type B is a distinct variant with endocrine differentiation. In addition, glycoproteins MUC2 and MUC6 are predominantly expressed in mucinous (colloid) carcinoma; ductal carcinoma in situ is not often found in this setting. 

NCCN recommends multidisciplinary care and development of a personalized survivorship treatment plan, which includes a customized summary of possible long-term treatment toxicities. In addition, multidisciplinary care coordination encourages close follow-up that helps patients adhere to their medications and stay current with ongoing screening.

Breast-conserving surgery and local radiation therapy are often the two modalities used to treat mucinous (colloid) carcinoma, especially because prognosis is so favorable. NCCN recommends the consideration of adjuvant endocrine treatment for patients with pure mucinous tumors that are HER2-negative and ER-positive and/or PR-positive; staged at pT1, pT2, or pT3, and pN0 or pN1mi; and ≤ 2.9 cm. Adjuvant endocrine therapy is recommended for patients with the same disease characteristics whose tumor is ≥ 3 cm.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

A lack of standardized blood pressure training among doctors, physician assistants, nurses, and other health care professionals is preventing the country’s medical community from curbing hypertension, according to the American Medical Association. Hypertension affects about half of U.S. adults and is a leading contributor to cardiovascular disease.

First-year medical students typically read about BP measurement in a textbook and possibly attend a lecture before practicing using a manual cuff a few times on classmates, said Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles.

The dearth of BP instruction is alarming because inaccurate readings contribute to under- and overtreatment of hypertension, she said in an interview.

The AMA hopes $100,000 in grants to five health education schools will help improve BP instruction. The group recently announced it would give $20,000 each to five schools that train health professionals, expanding on a 2021 program to improve BP measurement training.

The new grants for interactive lessons will benefit nearly 5,000 students from Johns Hopkins University, Baltimore; Nova Southeastern University, Fort Lauderdale, Fla.; University of Washington, Seattle; Stony Brook (N.Y.) University; and the University of Pittsburgh.

In a 2021 survey of 571 clinicians, most of whom were cardiologists, Dr. Gulati found that only 23% performed accurate BP measurements despite the majority saying they trusted BP readings taken in their clinic. Accurate readings were defined as routinely checking BP in both arms, checking BP at least twice each visit, and waiting 5 minutes before taking the reading.

Med students fare no better when it comes to BP skills. In a 2017 study of 159 students from medical schools in 37 states, only one student demonstrated proficiency in all 11 elements necessary to measure BP accurately. Students, on average, performed just four of them correctly.

The elements of proper BP measurement include patients resting for 5 minutes before the measurement with legs uncrossed, feet on floor, and arm supported, not talking, reading, or using cell phone; BP taken in both arms with correct size of cuff placed over bare arm; and identifying BP from the arm with the higher reading as clinically more important and as the one to use for future readings.

Manual BP readings require an appropriately sized BP cuff, a sphygmomanometer, and a clinician skilled in using a stethoscope and auscultatory method. Meanwhile, automated readings require a clinician to place the cuff, but a digital device collects the measurement. Though preference depends on the setting and clinician, automated readings are more common. In Dr. Gulati’s study, automated BP assessment was used by 58% of respondents.

Depending on the BP device and technique, significant variations in readings can occur. In a 2021 study, Current Hypertension Reports found that automated readings may more closely reflect the patient’s baseline BP and produce results similar to ambulatory monitoring by a medical professional. An earlier JAMA Internal Medicine analysis found that clinicians’ manual readings reflect higher BP measurements than automated readings.

Though the AMA offers a free online series on BP measurement for students, making the training available to more health care team members can help prevent hypertension, said Kate Kirley, MD, director of the AMA’s chronic disease prevention and programs.

Concern over the lack of standardized BP techniques isn’t new. In 2019, the American Heart Association and the AMA created an online BP course for health care workers. Two years later, the AMA offered grants to five medical schools for training courses.

Most of the new training sessions already on the AMA website take students about 15 minutes to complete. Dr. Kirley says because equipment varies across settings, participants will learn how to conduct manual, semi-automated, and automated office BP readings and identify workarounds for less-than-ideal room setups that can skew results. They will also explore how to guide patients in performing BP readings at home.

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

A lack of standardized blood pressure training among doctors, physician assistants, nurses, and other health care professionals is preventing the country’s medical community from curbing hypertension, according to the American Medical Association. Hypertension affects about half of U.S. adults and is a leading contributor to cardiovascular disease.

First-year medical students typically read about BP measurement in a textbook and possibly attend a lecture before practicing using a manual cuff a few times on classmates, said Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles.

The dearth of BP instruction is alarming because inaccurate readings contribute to under- and overtreatment of hypertension, she said in an interview.

The AMA hopes $100,000 in grants to five health education schools will help improve BP instruction. The group recently announced it would give $20,000 each to five schools that train health professionals, expanding on a 2021 program to improve BP measurement training.

The new grants for interactive lessons will benefit nearly 5,000 students from Johns Hopkins University, Baltimore; Nova Southeastern University, Fort Lauderdale, Fla.; University of Washington, Seattle; Stony Brook (N.Y.) University; and the University of Pittsburgh.

In a 2021 survey of 571 clinicians, most of whom were cardiologists, Dr. Gulati found that only 23% performed accurate BP measurements despite the majority saying they trusted BP readings taken in their clinic. Accurate readings were defined as routinely checking BP in both arms, checking BP at least twice each visit, and waiting 5 minutes before taking the reading.

Med students fare no better when it comes to BP skills. In a 2017 study of 159 students from medical schools in 37 states, only one student demonstrated proficiency in all 11 elements necessary to measure BP accurately. Students, on average, performed just four of them correctly.

The elements of proper BP measurement include patients resting for 5 minutes before the measurement with legs uncrossed, feet on floor, and arm supported, not talking, reading, or using cell phone; BP taken in both arms with correct size of cuff placed over bare arm; and identifying BP from the arm with the higher reading as clinically more important and as the one to use for future readings.

Manual BP readings require an appropriately sized BP cuff, a sphygmomanometer, and a clinician skilled in using a stethoscope and auscultatory method. Meanwhile, automated readings require a clinician to place the cuff, but a digital device collects the measurement. Though preference depends on the setting and clinician, automated readings are more common. In Dr. Gulati’s study, automated BP assessment was used by 58% of respondents.

Depending on the BP device and technique, significant variations in readings can occur. In a 2021 study, Current Hypertension Reports found that automated readings may more closely reflect the patient’s baseline BP and produce results similar to ambulatory monitoring by a medical professional. An earlier JAMA Internal Medicine analysis found that clinicians’ manual readings reflect higher BP measurements than automated readings.

Though the AMA offers a free online series on BP measurement for students, making the training available to more health care team members can help prevent hypertension, said Kate Kirley, MD, director of the AMA’s chronic disease prevention and programs.

Concern over the lack of standardized BP techniques isn’t new. In 2019, the American Heart Association and the AMA created an online BP course for health care workers. Two years later, the AMA offered grants to five medical schools for training courses.

Most of the new training sessions already on the AMA website take students about 15 minutes to complete. Dr. Kirley says because equipment varies across settings, participants will learn how to conduct manual, semi-automated, and automated office BP readings and identify workarounds for less-than-ideal room setups that can skew results. They will also explore how to guide patients in performing BP readings at home.

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

A lack of standardized blood pressure training among doctors, physician assistants, nurses, and other health care professionals is preventing the country’s medical community from curbing hypertension, according to the American Medical Association. Hypertension affects about half of U.S. adults and is a leading contributor to cardiovascular disease.

First-year medical students typically read about BP measurement in a textbook and possibly attend a lecture before practicing using a manual cuff a few times on classmates, said Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles.

The dearth of BP instruction is alarming because inaccurate readings contribute to under- and overtreatment of hypertension, she said in an interview.

The AMA hopes $100,000 in grants to five health education schools will help improve BP instruction. The group recently announced it would give $20,000 each to five schools that train health professionals, expanding on a 2021 program to improve BP measurement training.

The new grants for interactive lessons will benefit nearly 5,000 students from Johns Hopkins University, Baltimore; Nova Southeastern University, Fort Lauderdale, Fla.; University of Washington, Seattle; Stony Brook (N.Y.) University; and the University of Pittsburgh.

In a 2021 survey of 571 clinicians, most of whom were cardiologists, Dr. Gulati found that only 23% performed accurate BP measurements despite the majority saying they trusted BP readings taken in their clinic. Accurate readings were defined as routinely checking BP in both arms, checking BP at least twice each visit, and waiting 5 minutes before taking the reading.

Med students fare no better when it comes to BP skills. In a 2017 study of 159 students from medical schools in 37 states, only one student demonstrated proficiency in all 11 elements necessary to measure BP accurately. Students, on average, performed just four of them correctly.

The elements of proper BP measurement include patients resting for 5 minutes before the measurement with legs uncrossed, feet on floor, and arm supported, not talking, reading, or using cell phone; BP taken in both arms with correct size of cuff placed over bare arm; and identifying BP from the arm with the higher reading as clinically more important and as the one to use for future readings.

Manual BP readings require an appropriately sized BP cuff, a sphygmomanometer, and a clinician skilled in using a stethoscope and auscultatory method. Meanwhile, automated readings require a clinician to place the cuff, but a digital device collects the measurement. Though preference depends on the setting and clinician, automated readings are more common. In Dr. Gulati’s study, automated BP assessment was used by 58% of respondents.

Depending on the BP device and technique, significant variations in readings can occur. In a 2021 study, Current Hypertension Reports found that automated readings may more closely reflect the patient’s baseline BP and produce results similar to ambulatory monitoring by a medical professional. An earlier JAMA Internal Medicine analysis found that clinicians’ manual readings reflect higher BP measurements than automated readings.

Though the AMA offers a free online series on BP measurement for students, making the training available to more health care team members can help prevent hypertension, said Kate Kirley, MD, director of the AMA’s chronic disease prevention and programs.

Concern over the lack of standardized BP techniques isn’t new. In 2019, the American Heart Association and the AMA created an online BP course for health care workers. Two years later, the AMA offered grants to five medical schools for training courses.

Most of the new training sessions already on the AMA website take students about 15 minutes to complete. Dr. Kirley says because equipment varies across settings, participants will learn how to conduct manual, semi-automated, and automated office BP readings and identify workarounds for less-than-ideal room setups that can skew results. They will also explore how to guide patients in performing BP readings at home.

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

The hugely popular weight loss agent semaglutide (approved as Wegovy for weight loss; Ozempic for type 2 diabetes; Novo Nordisk) received a pair of drug safety–related labeling additions from the Food and Drug Administration in late September for the Ozempic formulation.

The FDA added a warning to the drug-interaction section of the Ozempic label that reiterates a warning that is already in place in other label sections, reinforcing the message that the glucagon-like peptide-1 (GLP-1) receptor agonist Ozempic can potentially interact with the action of certain other agents to increase a person’s risk for hypoglycemia.

The added text says: “Ozempic stimulates insulin release in the presence of elevated blood glucose concentrations. Patients receiving Ozempic in combination with an insulin secretagogue (for instance, sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia.”

This text was already included in both the “Warning and Precautions” and the “Adverse Reactions” sections of the label. The warning also advises, “The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.”

Reports of ileus episodes after approval

The second addition concerns a new adverse reaction that was identified during the postmarketing experience.

The FDA has received more than 8,500 reports of gastrointestinal issues among patients prescribed glucagon-like peptide-1 (GLP-1) receptor agonists. Ileus is mentioned in 33 cases, including two deaths, associated with semaglutide. The FDA stopped short of saying there is a direct link between the drug and intestinal blockages.

“Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure,” the FDA stated in its approval of the label update.

The same warning for the risk of intestinal blockages is already listed on the labels for tirzepatide (Mounjaro, Lilly) and semaglutide injection 2.4 mg (Wegovy, Novo Nordisk).

The label change comes after a Louisiana woman filed a lawsuit in August that claims she was “severely injured” after using Mounjaro and Ozempic. She claimed the drug makers failed to disclose risks of vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.

*Correction, 10/3/23: An earlier version of this article misstated the semaglutide formulation that received the updates. 

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

The hugely popular weight loss agent semaglutide (approved as Wegovy for weight loss; Ozempic for type 2 diabetes; Novo Nordisk) received a pair of drug safety–related labeling additions from the Food and Drug Administration in late September for the Ozempic formulation.

The FDA added a warning to the drug-interaction section of the Ozempic label that reiterates a warning that is already in place in other label sections, reinforcing the message that the glucagon-like peptide-1 (GLP-1) receptor agonist Ozempic can potentially interact with the action of certain other agents to increase a person’s risk for hypoglycemia.

The added text says: “Ozempic stimulates insulin release in the presence of elevated blood glucose concentrations. Patients receiving Ozempic in combination with an insulin secretagogue (for instance, sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia.”

This text was already included in both the “Warning and Precautions” and the “Adverse Reactions” sections of the label. The warning also advises, “The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.”

Reports of ileus episodes after approval

The second addition concerns a new adverse reaction that was identified during the postmarketing experience.

The FDA has received more than 8,500 reports of gastrointestinal issues among patients prescribed glucagon-like peptide-1 (GLP-1) receptor agonists. Ileus is mentioned in 33 cases, including two deaths, associated with semaglutide. The FDA stopped short of saying there is a direct link between the drug and intestinal blockages.

“Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure,” the FDA stated in its approval of the label update.

The same warning for the risk of intestinal blockages is already listed on the labels for tirzepatide (Mounjaro, Lilly) and semaglutide injection 2.4 mg (Wegovy, Novo Nordisk).

The label change comes after a Louisiana woman filed a lawsuit in August that claims she was “severely injured” after using Mounjaro and Ozempic. She claimed the drug makers failed to disclose risks of vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.

*Correction, 10/3/23: An earlier version of this article misstated the semaglutide formulation that received the updates. 

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

The hugely popular weight loss agent semaglutide (approved as Wegovy for weight loss; Ozempic for type 2 diabetes; Novo Nordisk) received a pair of drug safety–related labeling additions from the Food and Drug Administration in late September for the Ozempic formulation.

The FDA added a warning to the drug-interaction section of the Ozempic label that reiterates a warning that is already in place in other label sections, reinforcing the message that the glucagon-like peptide-1 (GLP-1) receptor agonist Ozempic can potentially interact with the action of certain other agents to increase a person’s risk for hypoglycemia.

The added text says: “Ozempic stimulates insulin release in the presence of elevated blood glucose concentrations. Patients receiving Ozempic in combination with an insulin secretagogue (for instance, sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia.”

This text was already included in both the “Warning and Precautions” and the “Adverse Reactions” sections of the label. The warning also advises, “The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.”

Reports of ileus episodes after approval

The second addition concerns a new adverse reaction that was identified during the postmarketing experience.

The FDA has received more than 8,500 reports of gastrointestinal issues among patients prescribed glucagon-like peptide-1 (GLP-1) receptor agonists. Ileus is mentioned in 33 cases, including two deaths, associated with semaglutide. The FDA stopped short of saying there is a direct link between the drug and intestinal blockages.

“Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure,” the FDA stated in its approval of the label update.

The same warning for the risk of intestinal blockages is already listed on the labels for tirzepatide (Mounjaro, Lilly) and semaglutide injection 2.4 mg (Wegovy, Novo Nordisk).

The label change comes after a Louisiana woman filed a lawsuit in August that claims she was “severely injured” after using Mounjaro and Ozempic. She claimed the drug makers failed to disclose risks of vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.

*Correction, 10/3/23: An earlier version of this article misstated the semaglutide formulation that received the updates. 

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

While artificial intelligence (AI) appears to be on its way to transforming all fields of medicine, its potential benefits in endocrinology, with its substantial complexity, may be uniquely important. However, hurdles encountered with the latest AI iterations of chatbots underscore the need to proceed with caution.

“In contrast to other medical fields, endocrinology is not connected to a single organ structure; rather, it is a complicated biological system of hormones and metabolites, [intertwined with] various receptors, signaling pathways and intricate feedback mechanisms,” explained the authors of a recent article on the issue in Nature Reviews Endocrinology.

With interconnections that are “often beyond the comprehension and reasoning capabilities of the human brain, AI [is anticipated] to be exceptionally well-suited to tackle this remarkable heterogeneity and complexity,” they wrote.

Since the first regulatory approvals for AI-based technology were granted back in 2015, endocrinology has already been revolutionized by AI-based tools, most notably with AI biosensors for continuous glucose monitoring systems alerting patients of glucose levels, and automated insulin-delivery systems.

AI-based machine learning has also ushered in improved detection and analysis of thyroid nodules and potential malignancies, with algorithms in the analysis of radiological test images enabling detection through a deeper analysis than can be applied with individual specialists.

Likewise, the benefits of AI in imaging extend to osteoporosis.

“Imaging certainly is one of the most promising fields, including (but not limited to) conventional radiography, computed tomography, and magnetic resonance tomography,” explained Hans Peter Dimai, MD, a professor of medicine and endocrinology at the Medical University of Graz (Austria), and the past president of the Austrian Bone and Mineral Society.

“A typical indication is fracture detection, not in terms of replacing expert radiologists or orthopedists but rather in terms of supporting those who are in specialist training,” he said in an interview.

“Particularly the underdiagnosis of vertebral fractures has been an issue in past decades, with dramatic implications for the individual, since the first vertebral fracture would multiply the risk for any future fracture, and therefore requires immediate action from a physician’s side.”

The areas expected to further benefit from AI continue to grow as systems evolve, with advances being reported across a variety of endocrinologic conditions.

Papillary thyroid cancer (PTC): Central lymph node metastasis of papillary thyroid cancer is predictive of tumor recurrence and overall survival in PTC. However, few tests are able to diagnose the metastasis in the cancer with high accuracy. Using a convolutional neural network prediction model built with a deep-learning algorithm, researchers described high diagnostic sensitivity and specificity of a model, as reported in a study published in Feburary. The prediction model, developed using genetic mutations and clinicopathologic factors, showed high prediction efficacy, with validation in subclinical as well as clinical metastasis groups, suggesting broad applicability.

Adrenal tumors: Adrenal incidentalomas, or masses that are incidentally discovered when performing abdominal imaging for other reasons, can be a perplexing clinical challenge. Discovery of these is increasing as imaging technology advances. However, an AI-based machine learning approach utilizing CT is being developed to differentiate between subclinical pheochromocytoma and lipid-poor adenomas. As reported in a 2022 study, the prediction model scoring system used traditional radiological features on CT images to provide for a noninvasive method in assisting in the diagnosis and providing personalized care for people with adrenal tumors.

Osteoporosis – bone mineral density (BMD): In the diagnosis of osteoporosis, the measurement of BMD using dual-energy x-ray absorptiometry (DXA) is the gold standard. However, the availability of DXA devices in many countries is inadequate, leaving an unmet need for alternative approaches. But one AI-based algorithm shows promising diagnostic accuracy, compared with DXA, potentially providing a low-cost screening alternative for the early diagnosis of osteoporosis.  

Osteoporosis – Fracture Risk Assessment Tool (FRAX): In fracture risk and prevention, the free FRAX tool, available online, is the gold standard and recommended in nearly all osteoporosis guidelines. However, several studies on AI-based tools show some benefit over FRAX, including one approach using longitudinal data with conventional spine radiographs, showing predictive accuracy that exceeds FRAX.  

Osteoporosis – treatment: And for the often challenging process of treatment decision-making in osteoporosis, AI-based software, developed from more than 15,000 osteoporosis patients followed over 10 years, shows high accuracy in the prediction of response to treatment in terms of BMD increase, as described in another study. “Our results show that it is feasible to use a combination of electronic medical records–derived information to develop a machine-learning algorithm to predict a BMD response following osteoporosis treatment,” the authors reported. “This alternative approach can aid physicians to select an optimal therapeutic regimen in order to maximize a patient-specific treatment outcome.”
 

Chatbot wrinkles

The prospects of large language models (LLMs) and ChatGPT unleash the potential to understand and generate text in a similar capacity as humans. Although controversial, they could likewise be compelling.

However, such systems can be vastly more complex than earlier AI-based tools, and some studies are illustrating the kinds of stumbling blocks that need to be overcome.

For instance, in a study published in May, researchers explored the potential of ChatGPT 4.0 to synthesize clinical guidelines for diabetic ketoacidosis from three different sources to reflect the latest evidence and local context.

Such efforts are important but can be very resource-intensive when conducted without the use of AI assistance.

The study’s results showed that, although ChatGPT was able to generate a comprehensive table comparing the guidelines, there were multiple recurrent errors in misreporting and nonreporting, as well as inconsistencies, “rendering the results unreliable,” the authors wrote.

“Although ChatGPT demonstrates the potential for the synthesis of clinical guidelines, the presence of multiple recurrent errors and inconsistencies underscores the need for expert human intervention and validation,” the authors concluded.

Likewise, other research using ChatGPT for use in vitreoretinal diseases, including diabetic retinopathy, further demonstrated disappointing results, with the technology showing the chatbot provided completely accurate responses to only 8 (15.4%) of 52 questions, with some responses containing inappropriate or potentially harmful medical advice.

“For example, in response to ‘How do you get rid of epiretinal membrane?’, the platform described vitrectomy but also included incorrect options of injection therapy and laser therapy,” the authors wrote.

“The study highlights the limitations of using ChatGPT for the adaptation of clinical guidelines without expert human intervention,” they concluded.

And in research published in August that looked at the ability of ChatGPT to interpret guidelines – in this case 26 diagnosis descriptions from the National Comprehensive Cancer Network – results showed that as many as one-third of treatments recommended by the chatbot were at least partially not concordant with information stated in the NCCN guidelines, with recommendations varying based on how the question about treatment was presented.

“Clinicians should advise patients that LLM chatbots are not a reliable source of treatment information,” the authors wrote.
 

Diversity concerns

Among the most prominent concerns about chatbot inaccuracy has been the known lack of racial and ethnic diversity in large databases utilized in developing AI systems, potentially resulting in critical flaws in the information the systems produce.

In an editorial published with the NCCN guideline study, Atul Butte, MD, PhD, from the University of California, San Francisco, noted that the shortcomings should be weighed with the potential benefits.

“There is no doubt that AI and LLMs are not yet perfect, and they carry biases that will need to be addressed,” Dr. Butte wrote. “These algorithms will need to be carefully monitored as they are brought into health systems, [but] this does not alter the potential of how they can improve care for both the haves and have-nots of health care.”

In a comment, Dr. Butte elaborated that, once the system flaws are refined, a key benefit will be the broader application of top standards of care to more patients who may have limited resources.

“It is a privilege to get the very best level of care from the very best centers, but that privilege is not distributable to all right now,” Dr. Butte said.

“The real potential of LLMs and AI will be their ability to be trained from the patient, clinical, and outcomes data from the very best centers, and then used to deliver the best care through digital tools to all patients, especially to those without access to the best care or [those with] limited resources,” he said.

Further commenting on the issue of potential bias with chatbots, Matthew Li, MD, from the University of Alberta, Edmonton, said that awareness of the nature of the problem and need for diversity in data for training and testing AI-systems issues appears to be improving.

“Thanks to much research on this topic in recent years, I think most AI researchers in medicine are at least aware of these challenges now, which was not the case only a few years ago,” he said in an interview.

Across specialties, “the careful deployment of AI tools accounting for issues regarding AI model generalization, biases, and performance drift will be critical for ensuring safe and fair patient care,” Dr. Li noted.

On a broader level is the ongoing general concern of the potential for over-reliance on the technology by clinicians. For example, a recent study showing radiologists across all experience levels reading mammograms were prone to automation bias when being supported by an AI-based system.

“Concerns regarding over-reliance on AI remain,” said Dr. Li, who coauthored a study published in June on the issue.

“Ongoing research into and monitoring of the impact of AI systems as they are developed and deployed will be important to ensure safe patient care moving forward,” he said.

Ultimately, the clinical benefit of AI systems to patients should be the bottom line, Dr. Dimai added.

“In my opinion, the clinical relevance, i.e., the benefit for patients and/or physicians of a to-be-developed AI tool, must be clearly proven before its development starts and first clinical studies are carried out,” he said.

“This is not always the case,” Dr. Dimai said. “In other words, innovation per se should not be the only rationale and driving force for the development of such tools.”

Dr. Li, an associate editor for the journal Radiology: Artificial Intelligence, reports no relevant financial relationships. Dr. Dimai is a member of the key medical advisor team of Image Biopsy Lab.

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

While artificial intelligence (AI) appears to be on its way to transforming all fields of medicine, its potential benefits in endocrinology, with its substantial complexity, may be uniquely important. However, hurdles encountered with the latest AI iterations of chatbots underscore the need to proceed with caution.

“In contrast to other medical fields, endocrinology is not connected to a single organ structure; rather, it is a complicated biological system of hormones and metabolites, [intertwined with] various receptors, signaling pathways and intricate feedback mechanisms,” explained the authors of a recent article on the issue in Nature Reviews Endocrinology.

With interconnections that are “often beyond the comprehension and reasoning capabilities of the human brain, AI [is anticipated] to be exceptionally well-suited to tackle this remarkable heterogeneity and complexity,” they wrote.

Since the first regulatory approvals for AI-based technology were granted back in 2015, endocrinology has already been revolutionized by AI-based tools, most notably with AI biosensors for continuous glucose monitoring systems alerting patients of glucose levels, and automated insulin-delivery systems.

AI-based machine learning has also ushered in improved detection and analysis of thyroid nodules and potential malignancies, with algorithms in the analysis of radiological test images enabling detection through a deeper analysis than can be applied with individual specialists.

Likewise, the benefits of AI in imaging extend to osteoporosis.

“Imaging certainly is one of the most promising fields, including (but not limited to) conventional radiography, computed tomography, and magnetic resonance tomography,” explained Hans Peter Dimai, MD, a professor of medicine and endocrinology at the Medical University of Graz (Austria), and the past president of the Austrian Bone and Mineral Society.

“A typical indication is fracture detection, not in terms of replacing expert radiologists or orthopedists but rather in terms of supporting those who are in specialist training,” he said in an interview.

“Particularly the underdiagnosis of vertebral fractures has been an issue in past decades, with dramatic implications for the individual, since the first vertebral fracture would multiply the risk for any future fracture, and therefore requires immediate action from a physician’s side.”

The areas expected to further benefit from AI continue to grow as systems evolve, with advances being reported across a variety of endocrinologic conditions.

Papillary thyroid cancer (PTC): Central lymph node metastasis of papillary thyroid cancer is predictive of tumor recurrence and overall survival in PTC. However, few tests are able to diagnose the metastasis in the cancer with high accuracy. Using a convolutional neural network prediction model built with a deep-learning algorithm, researchers described high diagnostic sensitivity and specificity of a model, as reported in a study published in Feburary. The prediction model, developed using genetic mutations and clinicopathologic factors, showed high prediction efficacy, with validation in subclinical as well as clinical metastasis groups, suggesting broad applicability.

Adrenal tumors: Adrenal incidentalomas, or masses that are incidentally discovered when performing abdominal imaging for other reasons, can be a perplexing clinical challenge. Discovery of these is increasing as imaging technology advances. However, an AI-based machine learning approach utilizing CT is being developed to differentiate between subclinical pheochromocytoma and lipid-poor adenomas. As reported in a 2022 study, the prediction model scoring system used traditional radiological features on CT images to provide for a noninvasive method in assisting in the diagnosis and providing personalized care for people with adrenal tumors.

Osteoporosis – bone mineral density (BMD): In the diagnosis of osteoporosis, the measurement of BMD using dual-energy x-ray absorptiometry (DXA) is the gold standard. However, the availability of DXA devices in many countries is inadequate, leaving an unmet need for alternative approaches. But one AI-based algorithm shows promising diagnostic accuracy, compared with DXA, potentially providing a low-cost screening alternative for the early diagnosis of osteoporosis.  

Osteoporosis – Fracture Risk Assessment Tool (FRAX): In fracture risk and prevention, the free FRAX tool, available online, is the gold standard and recommended in nearly all osteoporosis guidelines. However, several studies on AI-based tools show some benefit over FRAX, including one approach using longitudinal data with conventional spine radiographs, showing predictive accuracy that exceeds FRAX.  

Osteoporosis – treatment: And for the often challenging process of treatment decision-making in osteoporosis, AI-based software, developed from more than 15,000 osteoporosis patients followed over 10 years, shows high accuracy in the prediction of response to treatment in terms of BMD increase, as described in another study. “Our results show that it is feasible to use a combination of electronic medical records–derived information to develop a machine-learning algorithm to predict a BMD response following osteoporosis treatment,” the authors reported. “This alternative approach can aid physicians to select an optimal therapeutic regimen in order to maximize a patient-specific treatment outcome.”
 

Chatbot wrinkles

The prospects of large language models (LLMs) and ChatGPT unleash the potential to understand and generate text in a similar capacity as humans. Although controversial, they could likewise be compelling.

However, such systems can be vastly more complex than earlier AI-based tools, and some studies are illustrating the kinds of stumbling blocks that need to be overcome.

For instance, in a study published in May, researchers explored the potential of ChatGPT 4.0 to synthesize clinical guidelines for diabetic ketoacidosis from three different sources to reflect the latest evidence and local context.

Such efforts are important but can be very resource-intensive when conducted without the use of AI assistance.

The study’s results showed that, although ChatGPT was able to generate a comprehensive table comparing the guidelines, there were multiple recurrent errors in misreporting and nonreporting, as well as inconsistencies, “rendering the results unreliable,” the authors wrote.

“Although ChatGPT demonstrates the potential for the synthesis of clinical guidelines, the presence of multiple recurrent errors and inconsistencies underscores the need for expert human intervention and validation,” the authors concluded.

Likewise, other research using ChatGPT for use in vitreoretinal diseases, including diabetic retinopathy, further demonstrated disappointing results, with the technology showing the chatbot provided completely accurate responses to only 8 (15.4%) of 52 questions, with some responses containing inappropriate or potentially harmful medical advice.

“For example, in response to ‘How do you get rid of epiretinal membrane?’, the platform described vitrectomy but also included incorrect options of injection therapy and laser therapy,” the authors wrote.

“The study highlights the limitations of using ChatGPT for the adaptation of clinical guidelines without expert human intervention,” they concluded.

And in research published in August that looked at the ability of ChatGPT to interpret guidelines – in this case 26 diagnosis descriptions from the National Comprehensive Cancer Network – results showed that as many as one-third of treatments recommended by the chatbot were at least partially not concordant with information stated in the NCCN guidelines, with recommendations varying based on how the question about treatment was presented.

“Clinicians should advise patients that LLM chatbots are not a reliable source of treatment information,” the authors wrote.
 

Diversity concerns

Among the most prominent concerns about chatbot inaccuracy has been the known lack of racial and ethnic diversity in large databases utilized in developing AI systems, potentially resulting in critical flaws in the information the systems produce.

In an editorial published with the NCCN guideline study, Atul Butte, MD, PhD, from the University of California, San Francisco, noted that the shortcomings should be weighed with the potential benefits.

“There is no doubt that AI and LLMs are not yet perfect, and they carry biases that will need to be addressed,” Dr. Butte wrote. “These algorithms will need to be carefully monitored as they are brought into health systems, [but] this does not alter the potential of how they can improve care for both the haves and have-nots of health care.”

In a comment, Dr. Butte elaborated that, once the system flaws are refined, a key benefit will be the broader application of top standards of care to more patients who may have limited resources.

“It is a privilege to get the very best level of care from the very best centers, but that privilege is not distributable to all right now,” Dr. Butte said.

“The real potential of LLMs and AI will be their ability to be trained from the patient, clinical, and outcomes data from the very best centers, and then used to deliver the best care through digital tools to all patients, especially to those without access to the best care or [those with] limited resources,” he said.

Further commenting on the issue of potential bias with chatbots, Matthew Li, MD, from the University of Alberta, Edmonton, said that awareness of the nature of the problem and need for diversity in data for training and testing AI-systems issues appears to be improving.

“Thanks to much research on this topic in recent years, I think most AI researchers in medicine are at least aware of these challenges now, which was not the case only a few years ago,” he said in an interview.

Across specialties, “the careful deployment of AI tools accounting for issues regarding AI model generalization, biases, and performance drift will be critical for ensuring safe and fair patient care,” Dr. Li noted.

On a broader level is the ongoing general concern of the potential for over-reliance on the technology by clinicians. For example, a recent study showing radiologists across all experience levels reading mammograms were prone to automation bias when being supported by an AI-based system.

“Concerns regarding over-reliance on AI remain,” said Dr. Li, who coauthored a study published in June on the issue.

“Ongoing research into and monitoring of the impact of AI systems as they are developed and deployed will be important to ensure safe patient care moving forward,” he said.

Ultimately, the clinical benefit of AI systems to patients should be the bottom line, Dr. Dimai added.

“In my opinion, the clinical relevance, i.e., the benefit for patients and/or physicians of a to-be-developed AI tool, must be clearly proven before its development starts and first clinical studies are carried out,” he said.

“This is not always the case,” Dr. Dimai said. “In other words, innovation per se should not be the only rationale and driving force for the development of such tools.”

Dr. Li, an associate editor for the journal Radiology: Artificial Intelligence, reports no relevant financial relationships. Dr. Dimai is a member of the key medical advisor team of Image Biopsy Lab.

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

While artificial intelligence (AI) appears to be on its way to transforming all fields of medicine, its potential benefits in endocrinology, with its substantial complexity, may be uniquely important. However, hurdles encountered with the latest AI iterations of chatbots underscore the need to proceed with caution.

“In contrast to other medical fields, endocrinology is not connected to a single organ structure; rather, it is a complicated biological system of hormones and metabolites, [intertwined with] various receptors, signaling pathways and intricate feedback mechanisms,” explained the authors of a recent article on the issue in Nature Reviews Endocrinology.

With interconnections that are “often beyond the comprehension and reasoning capabilities of the human brain, AI [is anticipated] to be exceptionally well-suited to tackle this remarkable heterogeneity and complexity,” they wrote.

Since the first regulatory approvals for AI-based technology were granted back in 2015, endocrinology has already been revolutionized by AI-based tools, most notably with AI biosensors for continuous glucose monitoring systems alerting patients of glucose levels, and automated insulin-delivery systems.

AI-based machine learning has also ushered in improved detection and analysis of thyroid nodules and potential malignancies, with algorithms in the analysis of radiological test images enabling detection through a deeper analysis than can be applied with individual specialists.

Likewise, the benefits of AI in imaging extend to osteoporosis.

“Imaging certainly is one of the most promising fields, including (but not limited to) conventional radiography, computed tomography, and magnetic resonance tomography,” explained Hans Peter Dimai, MD, a professor of medicine and endocrinology at the Medical University of Graz (Austria), and the past president of the Austrian Bone and Mineral Society.

“A typical indication is fracture detection, not in terms of replacing expert radiologists or orthopedists but rather in terms of supporting those who are in specialist training,” he said in an interview.

“Particularly the underdiagnosis of vertebral fractures has been an issue in past decades, with dramatic implications for the individual, since the first vertebral fracture would multiply the risk for any future fracture, and therefore requires immediate action from a physician’s side.”

The areas expected to further benefit from AI continue to grow as systems evolve, with advances being reported across a variety of endocrinologic conditions.

Papillary thyroid cancer (PTC): Central lymph node metastasis of papillary thyroid cancer is predictive of tumor recurrence and overall survival in PTC. However, few tests are able to diagnose the metastasis in the cancer with high accuracy. Using a convolutional neural network prediction model built with a deep-learning algorithm, researchers described high diagnostic sensitivity and specificity of a model, as reported in a study published in Feburary. The prediction model, developed using genetic mutations and clinicopathologic factors, showed high prediction efficacy, with validation in subclinical as well as clinical metastasis groups, suggesting broad applicability.

Adrenal tumors: Adrenal incidentalomas, or masses that are incidentally discovered when performing abdominal imaging for other reasons, can be a perplexing clinical challenge. Discovery of these is increasing as imaging technology advances. However, an AI-based machine learning approach utilizing CT is being developed to differentiate between subclinical pheochromocytoma and lipid-poor adenomas. As reported in a 2022 study, the prediction model scoring system used traditional radiological features on CT images to provide for a noninvasive method in assisting in the diagnosis and providing personalized care for people with adrenal tumors.

Osteoporosis – bone mineral density (BMD): In the diagnosis of osteoporosis, the measurement of BMD using dual-energy x-ray absorptiometry (DXA) is the gold standard. However, the availability of DXA devices in many countries is inadequate, leaving an unmet need for alternative approaches. But one AI-based algorithm shows promising diagnostic accuracy, compared with DXA, potentially providing a low-cost screening alternative for the early diagnosis of osteoporosis.  

Osteoporosis – Fracture Risk Assessment Tool (FRAX): In fracture risk and prevention, the free FRAX tool, available online, is the gold standard and recommended in nearly all osteoporosis guidelines. However, several studies on AI-based tools show some benefit over FRAX, including one approach using longitudinal data with conventional spine radiographs, showing predictive accuracy that exceeds FRAX.  

Osteoporosis – treatment: And for the often challenging process of treatment decision-making in osteoporosis, AI-based software, developed from more than 15,000 osteoporosis patients followed over 10 years, shows high accuracy in the prediction of response to treatment in terms of BMD increase, as described in another study. “Our results show that it is feasible to use a combination of electronic medical records–derived information to develop a machine-learning algorithm to predict a BMD response following osteoporosis treatment,” the authors reported. “This alternative approach can aid physicians to select an optimal therapeutic regimen in order to maximize a patient-specific treatment outcome.”
 

Chatbot wrinkles

The prospects of large language models (LLMs) and ChatGPT unleash the potential to understand and generate text in a similar capacity as humans. Although controversial, they could likewise be compelling.

However, such systems can be vastly more complex than earlier AI-based tools, and some studies are illustrating the kinds of stumbling blocks that need to be overcome.

For instance, in a study published in May, researchers explored the potential of ChatGPT 4.0 to synthesize clinical guidelines for diabetic ketoacidosis from three different sources to reflect the latest evidence and local context.

Such efforts are important but can be very resource-intensive when conducted without the use of AI assistance.

The study’s results showed that, although ChatGPT was able to generate a comprehensive table comparing the guidelines, there were multiple recurrent errors in misreporting and nonreporting, as well as inconsistencies, “rendering the results unreliable,” the authors wrote.

“Although ChatGPT demonstrates the potential for the synthesis of clinical guidelines, the presence of multiple recurrent errors and inconsistencies underscores the need for expert human intervention and validation,” the authors concluded.

Likewise, other research using ChatGPT for use in vitreoretinal diseases, including diabetic retinopathy, further demonstrated disappointing results, with the technology showing the chatbot provided completely accurate responses to only 8 (15.4%) of 52 questions, with some responses containing inappropriate or potentially harmful medical advice.

“For example, in response to ‘How do you get rid of epiretinal membrane?’, the platform described vitrectomy but also included incorrect options of injection therapy and laser therapy,” the authors wrote.

“The study highlights the limitations of using ChatGPT for the adaptation of clinical guidelines without expert human intervention,” they concluded.

And in research published in August that looked at the ability of ChatGPT to interpret guidelines – in this case 26 diagnosis descriptions from the National Comprehensive Cancer Network – results showed that as many as one-third of treatments recommended by the chatbot were at least partially not concordant with information stated in the NCCN guidelines, with recommendations varying based on how the question about treatment was presented.

“Clinicians should advise patients that LLM chatbots are not a reliable source of treatment information,” the authors wrote.
 

Diversity concerns

Among the most prominent concerns about chatbot inaccuracy has been the known lack of racial and ethnic diversity in large databases utilized in developing AI systems, potentially resulting in critical flaws in the information the systems produce.

In an editorial published with the NCCN guideline study, Atul Butte, MD, PhD, from the University of California, San Francisco, noted that the shortcomings should be weighed with the potential benefits.

“There is no doubt that AI and LLMs are not yet perfect, and they carry biases that will need to be addressed,” Dr. Butte wrote. “These algorithms will need to be carefully monitored as they are brought into health systems, [but] this does not alter the potential of how they can improve care for both the haves and have-nots of health care.”

In a comment, Dr. Butte elaborated that, once the system flaws are refined, a key benefit will be the broader application of top standards of care to more patients who may have limited resources.

“It is a privilege to get the very best level of care from the very best centers, but that privilege is not distributable to all right now,” Dr. Butte said.

“The real potential of LLMs and AI will be their ability to be trained from the patient, clinical, and outcomes data from the very best centers, and then used to deliver the best care through digital tools to all patients, especially to those without access to the best care or [those with] limited resources,” he said.

Further commenting on the issue of potential bias with chatbots, Matthew Li, MD, from the University of Alberta, Edmonton, said that awareness of the nature of the problem and need for diversity in data for training and testing AI-systems issues appears to be improving.

“Thanks to much research on this topic in recent years, I think most AI researchers in medicine are at least aware of these challenges now, which was not the case only a few years ago,” he said in an interview.

Across specialties, “the careful deployment of AI tools accounting for issues regarding AI model generalization, biases, and performance drift will be critical for ensuring safe and fair patient care,” Dr. Li noted.

On a broader level is the ongoing general concern of the potential for over-reliance on the technology by clinicians. For example, a recent study showing radiologists across all experience levels reading mammograms were prone to automation bias when being supported by an AI-based system.

“Concerns regarding over-reliance on AI remain,” said Dr. Li, who coauthored a study published in June on the issue.

“Ongoing research into and monitoring of the impact of AI systems as they are developed and deployed will be important to ensure safe patient care moving forward,” he said.

Ultimately, the clinical benefit of AI systems to patients should be the bottom line, Dr. Dimai added.

“In my opinion, the clinical relevance, i.e., the benefit for patients and/or physicians of a to-be-developed AI tool, must be clearly proven before its development starts and first clinical studies are carried out,” he said.

“This is not always the case,” Dr. Dimai said. “In other words, innovation per se should not be the only rationale and driving force for the development of such tools.”

Dr. Li, an associate editor for the journal Radiology: Artificial Intelligence, reports no relevant financial relationships. Dr. Dimai is a member of the key medical advisor team of Image Biopsy Lab.

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

TOPLINE:

Cutaneous immune-related adverse events are associated with improved overall and progression-free survival among patients treated with immune checkpoint inhibitors (ICIs).

METHODOLOGY:

• Emerging evidence suggests that the presence of cutaneous immune-related adverse events may be linked with favorable outcomes among patients with cancer who receive ICIs.
• Researchers conducted a systematic review and meta-analysis that included 23 studies and a total of 22,749 patients with cancer who received ICI treatment; studies compared outcomes among patients with and those without cutaneous immune-related adverse events.
• The major outcomes evaluated in the analysis were overall survival and progression-free survival (PFS); subgroup analyses assessed cutaneous immune-related adverse event type, cancer type, and other factors.

TAKEAWAY:

• The occurrence of cutaneous immune-related adverse events was associated with improved PFS (hazard ratio, 0.52; P < .001) and overall survival (HR, 0.61; P < .001).
• In the subgroup analysis, patients with eczematous (HR, 0.69), lichenoid or lichen planus–like skin lesions (HR, 0.51), pruritus without rash (HR, 0.70), psoriasis (HR, 0.63), or vitiligo (HR, 0.30) demonstrated a significant overall survival advantage. Vitiligo was the only adverse event associated with a PFS advantage (HR, 0.28).
• Among patients with melanoma, analyses revealed a significant association between the incidence of cutaneous immune-related adverse events and improved overall survival (HR, 0.51) and PFS (HR, 0.45). The authors highlighted similar findings among patients with non–small cell lung cancer (HR, 0.50 for overall survival and 0.61 for PFS).

IN PRACTICE:

“These data suggest that [cutaneous immune-related adverse events] may have useful prognostic value in ICI treatment,” the authors concluded.

SOURCE:

The analysis, led by Fei Wang, MD, Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, China, was published online in JAMA Dermatology.

LIMITATIONS:

Most of the data came from retrospective studies, and there were limited data on specific patient subgroups. The Egger tests, used to assess potential publication bias in meta-analyses, revealed publication bias.

DISCLOSURES:

No disclosures were reported. The study was supported by a grant from the Postgraduate Research and Practice Innovation Program of Jiangsu Province.

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

TOPLINE:

Cutaneous immune-related adverse events are associated with improved overall and progression-free survival among patients treated with immune checkpoint inhibitors (ICIs).

METHODOLOGY:

• Emerging evidence suggests that the presence of cutaneous immune-related adverse events may be linked with favorable outcomes among patients with cancer who receive ICIs.
• Researchers conducted a systematic review and meta-analysis that included 23 studies and a total of 22,749 patients with cancer who received ICI treatment; studies compared outcomes among patients with and those without cutaneous immune-related adverse events.
• The major outcomes evaluated in the analysis were overall survival and progression-free survival (PFS); subgroup analyses assessed cutaneous immune-related adverse event type, cancer type, and other factors.

TAKEAWAY:

• The occurrence of cutaneous immune-related adverse events was associated with improved PFS (hazard ratio, 0.52; P < .001) and overall survival (HR, 0.61; P < .001).
• In the subgroup analysis, patients with eczematous (HR, 0.69), lichenoid or lichen planus–like skin lesions (HR, 0.51), pruritus without rash (HR, 0.70), psoriasis (HR, 0.63), or vitiligo (HR, 0.30) demonstrated a significant overall survival advantage. Vitiligo was the only adverse event associated with a PFS advantage (HR, 0.28).
• Among patients with melanoma, analyses revealed a significant association between the incidence of cutaneous immune-related adverse events and improved overall survival (HR, 0.51) and PFS (HR, 0.45). The authors highlighted similar findings among patients with non–small cell lung cancer (HR, 0.50 for overall survival and 0.61 for PFS).

IN PRACTICE:

“These data suggest that [cutaneous immune-related adverse events] may have useful prognostic value in ICI treatment,” the authors concluded.

SOURCE:

The analysis, led by Fei Wang, MD, Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, China, was published online in JAMA Dermatology.

LIMITATIONS:

Most of the data came from retrospective studies, and there were limited data on specific patient subgroups. The Egger tests, used to assess potential publication bias in meta-analyses, revealed publication bias.

DISCLOSURES:

No disclosures were reported. The study was supported by a grant from the Postgraduate Research and Practice Innovation Program of Jiangsu Province.

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

TOPLINE:

Cutaneous immune-related adverse events are associated with improved overall and progression-free survival among patients treated with immune checkpoint inhibitors (ICIs).

METHODOLOGY:

• Emerging evidence suggests that the presence of cutaneous immune-related adverse events may be linked with favorable outcomes among patients with cancer who receive ICIs.
• Researchers conducted a systematic review and meta-analysis that included 23 studies and a total of 22,749 patients with cancer who received ICI treatment; studies compared outcomes among patients with and those without cutaneous immune-related adverse events.
• The major outcomes evaluated in the analysis were overall survival and progression-free survival (PFS); subgroup analyses assessed cutaneous immune-related adverse event type, cancer type, and other factors.

TAKEAWAY:

• The occurrence of cutaneous immune-related adverse events was associated with improved PFS (hazard ratio, 0.52; P < .001) and overall survival (HR, 0.61; P < .001).
• In the subgroup analysis, patients with eczematous (HR, 0.69), lichenoid or lichen planus–like skin lesions (HR, 0.51), pruritus without rash (HR, 0.70), psoriasis (HR, 0.63), or vitiligo (HR, 0.30) demonstrated a significant overall survival advantage. Vitiligo was the only adverse event associated with a PFS advantage (HR, 0.28).
• Among patients with melanoma, analyses revealed a significant association between the incidence of cutaneous immune-related adverse events and improved overall survival (HR, 0.51) and PFS (HR, 0.45). The authors highlighted similar findings among patients with non–small cell lung cancer (HR, 0.50 for overall survival and 0.61 for PFS).

IN PRACTICE:

“These data suggest that [cutaneous immune-related adverse events] may have useful prognostic value in ICI treatment,” the authors concluded.

SOURCE:

The analysis, led by Fei Wang, MD, Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, China, was published online in JAMA Dermatology.

LIMITATIONS:

Most of the data came from retrospective studies, and there were limited data on specific patient subgroups. The Egger tests, used to assess potential publication bias in meta-analyses, revealed publication bias.

DISCLOSURES:

No disclosures were reported. The study was supported by a grant from the Postgraduate Research and Practice Innovation Program of Jiangsu Province.

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

TOPLINE:

The number of primary melanomas is not an independent risk factor for mortality.

METHODOLOGY:

• The difference in outcomes between people with multiple primary melanomas (MPMs) and a single primary melanoma (SPM) has not been established.
• To compare 10-year melanoma-specific mortality and overall mortality between people with MPMs and SPM, researchers drew from the Melanoma Patterns of Care study, a population-based observational analysis of residents in the state of New South Wales, Australia, who had a melanoma reported to the state cancer registry over 12 months in 2006-2007, and were followed up until 2018, for a median of almost 12 years.
• The researchers performed logistic regression analyses to assess 10-year melanoma-specific mortality differences between the two groups.

TAKEAWAY:

• Of 3,404 people included in the analysis, 2,830 had an SPM and 574 developed MPMs during follow-up.
• On multivariable regression adjusted for pathologic characteristics of the thickest lesion in the MPM group, no significant differences were seen in 10-year melanoma-specific mortality between the two groups (odds ratio, 0.85; 95% confidence interval, 0.58-1.24; P = .40).
• Sensitivity analyses adjusted for parameters of the first primary melanoma among patients with MPMs revealed similar findings (OR, 1.34; 95% CI, 0.92-1.96; P = .12).
• On multivariable analysis using data from the thickest lesion, factors independently associated with melanoma-specific mortality were male sex, disadvantaged socioeconomic status (based on location of residence), and Breslow thickness.
• Factors independently associated with 10-year overall mortality were like those seen in other studies and included sex, Breslow thickness, ulceration status, and socioeconomic disadvantage.

IN PRACTICE:

“The results of our study suggest that the number of primary melanomas is not an independent risk factor for mortality,” the researchers concluded. “In addition, the detection of melanoma at an early stage (with a thin Breslow thickness) rather than an intrinsic biologic factor remains the biggest influence on melanoma mortality after diagnosis of one or more melanomas.”

SOURCE:

Corresponding author Serigne N. Lo, PhD, of the Melanoma Institute Australia, led the research. The study was published in the Journal of the American Academy of Dermatology.

LIMITATIONS:

No adjustments for treatment modality were made in the study, and at baseline survey, effective systemic treatments for melanoma were not available.

DISCLOSURES:

This study was supported by the Australian National Health and Medical Research Council, Cancer Institute New South Wales, and the New South Wale State Government via a grant to the New South Wales Melanoma Network. Additional support was provided by Melanoma Institute Australia and the New South Wales Melanoma Network.
 

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

TOPLINE:

The number of primary melanomas is not an independent risk factor for mortality.

METHODOLOGY:

• The difference in outcomes between people with multiple primary melanomas (MPMs) and a single primary melanoma (SPM) has not been established.
• To compare 10-year melanoma-specific mortality and overall mortality between people with MPMs and SPM, researchers drew from the Melanoma Patterns of Care study, a population-based observational analysis of residents in the state of New South Wales, Australia, who had a melanoma reported to the state cancer registry over 12 months in 2006-2007, and were followed up until 2018, for a median of almost 12 years.
• The researchers performed logistic regression analyses to assess 10-year melanoma-specific mortality differences between the two groups.

TAKEAWAY:

• Of 3,404 people included in the analysis, 2,830 had an SPM and 574 developed MPMs during follow-up.
• On multivariable regression adjusted for pathologic characteristics of the thickest lesion in the MPM group, no significant differences were seen in 10-year melanoma-specific mortality between the two groups (odds ratio, 0.85; 95% confidence interval, 0.58-1.24; P = .40).
• Sensitivity analyses adjusted for parameters of the first primary melanoma among patients with MPMs revealed similar findings (OR, 1.34; 95% CI, 0.92-1.96; P = .12).
• On multivariable analysis using data from the thickest lesion, factors independently associated with melanoma-specific mortality were male sex, disadvantaged socioeconomic status (based on location of residence), and Breslow thickness.
• Factors independently associated with 10-year overall mortality were like those seen in other studies and included sex, Breslow thickness, ulceration status, and socioeconomic disadvantage.

IN PRACTICE:

“The results of our study suggest that the number of primary melanomas is not an independent risk factor for mortality,” the researchers concluded. “In addition, the detection of melanoma at an early stage (with a thin Breslow thickness) rather than an intrinsic biologic factor remains the biggest influence on melanoma mortality after diagnosis of one or more melanomas.”

SOURCE:

Corresponding author Serigne N. Lo, PhD, of the Melanoma Institute Australia, led the research. The study was published in the Journal of the American Academy of Dermatology.

LIMITATIONS:

No adjustments for treatment modality were made in the study, and at baseline survey, effective systemic treatments for melanoma were not available.

DISCLOSURES:

This study was supported by the Australian National Health and Medical Research Council, Cancer Institute New South Wales, and the New South Wale State Government via a grant to the New South Wales Melanoma Network. Additional support was provided by Melanoma Institute Australia and the New South Wales Melanoma Network.
 

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

TOPLINE:

The number of primary melanomas is not an independent risk factor for mortality.

METHODOLOGY:

• The difference in outcomes between people with multiple primary melanomas (MPMs) and a single primary melanoma (SPM) has not been established.
• To compare 10-year melanoma-specific mortality and overall mortality between people with MPMs and SPM, researchers drew from the Melanoma Patterns of Care study, a population-based observational analysis of residents in the state of New South Wales, Australia, who had a melanoma reported to the state cancer registry over 12 months in 2006-2007, and were followed up until 2018, for a median of almost 12 years.
• The researchers performed logistic regression analyses to assess 10-year melanoma-specific mortality differences between the two groups.

TAKEAWAY:

• Of 3,404 people included in the analysis, 2,830 had an SPM and 574 developed MPMs during follow-up.
• On multivariable regression adjusted for pathologic characteristics of the thickest lesion in the MPM group, no significant differences were seen in 10-year melanoma-specific mortality between the two groups (odds ratio, 0.85; 95% confidence interval, 0.58-1.24; P = .40).
• Sensitivity analyses adjusted for parameters of the first primary melanoma among patients with MPMs revealed similar findings (OR, 1.34; 95% CI, 0.92-1.96; P = .12).
• On multivariable analysis using data from the thickest lesion, factors independently associated with melanoma-specific mortality were male sex, disadvantaged socioeconomic status (based on location of residence), and Breslow thickness.
• Factors independently associated with 10-year overall mortality were like those seen in other studies and included sex, Breslow thickness, ulceration status, and socioeconomic disadvantage.

IN PRACTICE:

“The results of our study suggest that the number of primary melanomas is not an independent risk factor for mortality,” the researchers concluded. “In addition, the detection of melanoma at an early stage (with a thin Breslow thickness) rather than an intrinsic biologic factor remains the biggest influence on melanoma mortality after diagnosis of one or more melanomas.”

SOURCE:

Corresponding author Serigne N. Lo, PhD, of the Melanoma Institute Australia, led the research. The study was published in the Journal of the American Academy of Dermatology.

LIMITATIONS:

No adjustments for treatment modality were made in the study, and at baseline survey, effective systemic treatments for melanoma were not available.

DISCLOSURES:

This study was supported by the Australian National Health and Medical Research Council, Cancer Institute New South Wales, and the New South Wale State Government via a grant to the New South Wales Melanoma Network. Additional support was provided by Melanoma Institute Australia and the New South Wales Melanoma Network.
 

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

Transgender patients in the United States and Canada told researchers that they often face voyeuristic and stigmatizing treatment in medical clinics and they fear they’re getting substandard care.

“Transgender people feel that their care worsens when clinicians learn that they are transgender, and thus they often have to choose between stigma if clinicians learn that they are transgender and potentially ineffective clinical problem-solving if they do not,” said Yale Cancer Center instructor of medicine Ash B. Alpert, MD, MFA, lead author of the study, which was published in Annals of Family Medicine. For the qualitative study, researchers held seven online focus groups with 30 transgender adults (median age, 31; age range, 20-67; 40% people of color; and 47% with incomes of more than $40,000 a year). All but one were from the United States.

According to the study, the participants said clinicians often ask “irrelevant” questions, sometimes with intentions that appear voyeuristic. “I saw a pulmonologist earlier in the year and one of his first questions was, ‘When are you getting genital surgery?’ and I was like, ‘I’m here for my lungs,’ ” said a White, nonbinary participant. A White male participant said “As soon as I walk in, no matter what I’m there for, the first [order] of business is for them to determine my gender or sex assigned at birth ... and ... once they ... know they’re ... much more at ease.”

Participants also described how medical encounters went awry once clinicians realized they were transgender. “It wasn’t until after I told the doctor that I was on hormones for transition that I started being ‘he’d.’ ” Before that, it was “she,” said a Black transgender woman.

One participant, a Black person who declined to identify by gender, said “I don’t feel comfortable sharing medical records with physicians anyway because it’s a guarantee that I’m not gonna get services. So I lost [my medical records] and they’re good wherever they are now, far away from me.”

Ten participants were clinicians. “Many seemed concerned that transgender people are being put in distressing and difficult situations in medical settings and also seemed dubious that health care for transgender people would improve without a complete overhaul,” Dr. Alpert said.

In an interview, Boston University assistant professor of medicine C. Streed Jr., MD, MPH, who studies gender and health, praised the study. He said it plays an early role in revealing the problems faced by transgender people in the health system.

“We do not fully know the experience of transgender persons accessing care in various contexts, especially in specialty care such as oncology, pulmonology, nephrology, etc.” Dr. Streed said. “We do not know how they identify specialists who are welcoming, compassionate, and competent in care for transgender persons.”

The results aren’t surprising, Dr. Streed said, “given the lack of training in medical school, residency, and fellowship specific to the unique needs of transgender persons.”
 

How can clinicians improve interactions with transgender people?

What can clinicians do to help transgender patients feel comfortable? Dr. Alpert suggested they “ask [only] for medically relevant information and to explain to patients why it is medically relevant.”

“This is important because transgender people are often weighing the risks and benefits of disclosing information that could be used to stigmatize them,” Dr. Alpert said.

What if a clinician wants to create a personal connection with a patient by asking questions about their life? “If you as a clinician think it’s important to ask for nonmedical information to get to know a patient, explicitly clarify that your questions are optional and not medically relevant,” Dr. Alpert said. “That way patients have the ability to consent or not to questions that likely will not directly benefit their care.”

Dr. Streed offered a similar perspective. “Clinicians should only be asking questions of patients that will affect the care the patient is seeking and for which the clinician is trained to provide,” he said. “Having a transgender patient is not an opportunity for a clinician to satisfy their curiosity when it is not related to the care the patient is seeking or needs.”

More specifically, Dr. Streed offered an example: Clinicians should not be asking about a patient’s genitals if they are seeking care related to their asthma diagnosis.

Dr. Streed referred clinicians to resources from the American Medical Association and the Human Rights Campaign for guidelines on caring for transgender patients.

The study was funded by Conquer Cancer. The study authors and Dr. Streed have no relevant disclosures.
 

Transgender patients in the United States and Canada told researchers that they often face voyeuristic and stigmatizing treatment in medical clinics and they fear they’re getting substandard care.

“Transgender people feel that their care worsens when clinicians learn that they are transgender, and thus they often have to choose between stigma if clinicians learn that they are transgender and potentially ineffective clinical problem-solving if they do not,” said Yale Cancer Center instructor of medicine Ash B. Alpert, MD, MFA, lead author of the study, which was published in Annals of Family Medicine. For the qualitative study, researchers held seven online focus groups with 30 transgender adults (median age, 31; age range, 20-67; 40% people of color; and 47% with incomes of more than $40,000 a year). All but one were from the United States.

According to the study, the participants said clinicians often ask “irrelevant” questions, sometimes with intentions that appear voyeuristic. “I saw a pulmonologist earlier in the year and one of his first questions was, ‘When are you getting genital surgery?’ and I was like, ‘I’m here for my lungs,’ ” said a White, nonbinary participant. A White male participant said “As soon as I walk in, no matter what I’m there for, the first [order] of business is for them to determine my gender or sex assigned at birth ... and ... once they ... know they’re ... much more at ease.”

Participants also described how medical encounters went awry once clinicians realized they were transgender. “It wasn’t until after I told the doctor that I was on hormones for transition that I started being ‘he’d.’ ” Before that, it was “she,” said a Black transgender woman.

One participant, a Black person who declined to identify by gender, said “I don’t feel comfortable sharing medical records with physicians anyway because it’s a guarantee that I’m not gonna get services. So I lost [my medical records] and they’re good wherever they are now, far away from me.”

Ten participants were clinicians. “Many seemed concerned that transgender people are being put in distressing and difficult situations in medical settings and also seemed dubious that health care for transgender people would improve without a complete overhaul,” Dr. Alpert said.

In an interview, Boston University assistant professor of medicine C. Streed Jr., MD, MPH, who studies gender and health, praised the study. He said it plays an early role in revealing the problems faced by transgender people in the health system.

“We do not fully know the experience of transgender persons accessing care in various contexts, especially in specialty care such as oncology, pulmonology, nephrology, etc.” Dr. Streed said. “We do not know how they identify specialists who are welcoming, compassionate, and competent in care for transgender persons.”

The results aren’t surprising, Dr. Streed said, “given the lack of training in medical school, residency, and fellowship specific to the unique needs of transgender persons.”
 

How can clinicians improve interactions with transgender people?

What can clinicians do to help transgender patients feel comfortable? Dr. Alpert suggested they “ask [only] for medically relevant information and to explain to patients why it is medically relevant.”

“This is important because transgender people are often weighing the risks and benefits of disclosing information that could be used to stigmatize them,” Dr. Alpert said.

What if a clinician wants to create a personal connection with a patient by asking questions about their life? “If you as a clinician think it’s important to ask for nonmedical information to get to know a patient, explicitly clarify that your questions are optional and not medically relevant,” Dr. Alpert said. “That way patients have the ability to consent or not to questions that likely will not directly benefit their care.”

Dr. Streed offered a similar perspective. “Clinicians should only be asking questions of patients that will affect the care the patient is seeking and for which the clinician is trained to provide,” he said. “Having a transgender patient is not an opportunity for a clinician to satisfy their curiosity when it is not related to the care the patient is seeking or needs.”

More specifically, Dr. Streed offered an example: Clinicians should not be asking about a patient’s genitals if they are seeking care related to their asthma diagnosis.

Dr. Streed referred clinicians to resources from the American Medical Association and the Human Rights Campaign for guidelines on caring for transgender patients.

The study was funded by Conquer Cancer. The study authors and Dr. Streed have no relevant disclosures.
 

Transgender patients in the United States and Canada told researchers that they often face voyeuristic and stigmatizing treatment in medical clinics and they fear they’re getting substandard care.

“Transgender people feel that their care worsens when clinicians learn that they are transgender, and thus they often have to choose between stigma if clinicians learn that they are transgender and potentially ineffective clinical problem-solving if they do not,” said Yale Cancer Center instructor of medicine Ash B. Alpert, MD, MFA, lead author of the study, which was published in Annals of Family Medicine. For the qualitative study, researchers held seven online focus groups with 30 transgender adults (median age, 31; age range, 20-67; 40% people of color; and 47% with incomes of more than $40,000 a year). All but one were from the United States.

According to the study, the participants said clinicians often ask “irrelevant” questions, sometimes with intentions that appear voyeuristic. “I saw a pulmonologist earlier in the year and one of his first questions was, ‘When are you getting genital surgery?’ and I was like, ‘I’m here for my lungs,’ ” said a White, nonbinary participant. A White male participant said “As soon as I walk in, no matter what I’m there for, the first [order] of business is for them to determine my gender or sex assigned at birth ... and ... once they ... know they’re ... much more at ease.”

Participants also described how medical encounters went awry once clinicians realized they were transgender. “It wasn’t until after I told the doctor that I was on hormones for transition that I started being ‘he’d.’ ” Before that, it was “she,” said a Black transgender woman.

One participant, a Black person who declined to identify by gender, said “I don’t feel comfortable sharing medical records with physicians anyway because it’s a guarantee that I’m not gonna get services. So I lost [my medical records] and they’re good wherever they are now, far away from me.”

Ten participants were clinicians. “Many seemed concerned that transgender people are being put in distressing and difficult situations in medical settings and also seemed dubious that health care for transgender people would improve without a complete overhaul,” Dr. Alpert said.

In an interview, Boston University assistant professor of medicine C. Streed Jr., MD, MPH, who studies gender and health, praised the study. He said it plays an early role in revealing the problems faced by transgender people in the health system.

“We do not fully know the experience of transgender persons accessing care in various contexts, especially in specialty care such as oncology, pulmonology, nephrology, etc.” Dr. Streed said. “We do not know how they identify specialists who are welcoming, compassionate, and competent in care for transgender persons.”

The results aren’t surprising, Dr. Streed said, “given the lack of training in medical school, residency, and fellowship specific to the unique needs of transgender persons.”
 

How can clinicians improve interactions with transgender people?

What can clinicians do to help transgender patients feel comfortable? Dr. Alpert suggested they “ask [only] for medically relevant information and to explain to patients why it is medically relevant.”

“This is important because transgender people are often weighing the risks and benefits of disclosing information that could be used to stigmatize them,” Dr. Alpert said.

What if a clinician wants to create a personal connection with a patient by asking questions about their life? “If you as a clinician think it’s important to ask for nonmedical information to get to know a patient, explicitly clarify that your questions are optional and not medically relevant,” Dr. Alpert said. “That way patients have the ability to consent or not to questions that likely will not directly benefit their care.”

Dr. Streed offered a similar perspective. “Clinicians should only be asking questions of patients that will affect the care the patient is seeking and for which the clinician is trained to provide,” he said. “Having a transgender patient is not an opportunity for a clinician to satisfy their curiosity when it is not related to the care the patient is seeking or needs.”

More specifically, Dr. Streed offered an example: Clinicians should not be asking about a patient’s genitals if they are seeking care related to their asthma diagnosis.

Dr. Streed referred clinicians to resources from the American Medical Association and the Human Rights Campaign for guidelines on caring for transgender patients.

The study was funded by Conquer Cancer. The study authors and Dr. Streed have no relevant disclosures.
 

A revolutionary treatment for cancers may also be able to treat and reset the immune system to provide long-term remission or possibly even cure certain autoimmune diseases.

Chimeric antigen receptor (CAR) T-cell therapy has offered a novel approach to treating hematologic cancers since 2017, but there are early signs that these cellular immunotherapies could be repurposed for B-cell mediated autoimmune diseases.

In September of last year, researchers in Germany reported that five patients with refractory systemic lupus erythematosus (SLE) treated with CAR T-cell therapy all achieved drug-free remission. At the time of publication, no patients had relapsed for up to 17 months after treatment. The authors described seroconversion of antinuclear antibodies in two patients with the longest follow-up, “indicating that abrogation of autoimmune B-cell clones may lead to a more widespread correction of autoimmunity,” the researchers write.

In another case study published in June, researchers used CD-19 targeted CAR-T cells to treat a 41-year-old man with refractory antisynthetase syndrome with progressive myositis and interstitial lung disease. Six months after treatment, there were no signs of myositis on MRI and a chest CT scan showed full regression of alveolitis.

John Hopkins Medicine

Since then, two biotechnology companies – Cabaletta Bio in Philadelphia and Kyverna Therapeutics in Emeryville, Calif. – have already been granted fast-track designations from the U.S. Food and Drug Administration for CAR T-cell therapy for SLE and lupus nephritis. Bristol-Myers Squibb is also conducting a phase 1 trial in patients with severe, refractory SLE. Several biotechnology companies and hospitals in China are also conducting clinical trials for SLE. But this is only the tip of the iceberg regarding cellular therapies for autoimmune disease, said Max Konig, MD, PhD, an assistant professor of medicine in the division of rheumatology at Johns Hopkins University, Baltimore.

“It’s an incredibly exciting time. It’s unprecedented in the history of autoimmunity,” he noted.
 

A ‘reboot’ for the immune system

B-cell targeted therapies have been around since the early 2000s with drugs like rituximab, a monoclonal antibody medication that targets CD20, an antigen expressed on the surface of B cells. The CAR T cells currently available target another surface antigen, CD19, and are a much more potent therapy. Both are effective at depleting B cells in blood, but these engineered CD19-targeted T cells can reach B cells sitting in tissues in a way that antibody therapies cannot, Dr. Konig explained.

“If you have a patient with myositis, for example, where autoreactive B cells are sitting in the inflamed muscle, or a patient with rheumatoid arthritis, where you have disease-relevant B cells in hard-to-reach tissues like the synovium, those cells are much harder to deplete with an antibody, compared to a T cell that evolved to surveil and effectively kill in all tissues,” he explained.

In this process, T cells are collected from patients via leukapheresis and then re-engineered to express chimeric antigen receptors. A few days before these modified T cells are infused back into the patient, the patients are given a low-dose chemotherapy (lymphodepletion) regimen to help increase the effectiveness of the therapy. The one-time infusion is generally given on an inpatient basis, and patients are then monitored in hospital for side effects.

Once B cells are depleted, disease symptoms improve. But in the case studies published to date, once B cells re-emerge, they are naïve and no longer producing autoreactive B cells.
 

“Maybe it’s like a tabula rasa: You wipe [the B cells] out and start with a clean slate. Then, the immune system reboots, and now it’s working, whereas before it was messed up,” said Carl June, MD, who directs the Center for Cellular Immunotherapies at the at the University of Pennsylvania, Philadelphia. Dr. June and his research team led the development of CAR T-cell therapies for blood cancers.

The findings suggest that autoantibodies “might not be hardwired into the immune system,” he said.

But Dr. Konig stressed that we are still in the early days of clinical trials, and more research is necessary to understand the safety and efficacy of these therapies.

“There’s an incredible buzz around CAR T cells at the moment in rheumatology, which is great because I think that’s where the future is,” he said. “But we still need to learn how to appropriately apply these therapies in randomized, controlled trials.”

So far, the evidence behind CD19 CAR T-cell therapies in autoimmune disease is from case studies and phase 1 trials in a very small number of selected patients. (The upcoming Cabaletta and Kyverna trials in lupus will also be small, consisting of 12 patients each.)
 

Risks of intensive therapy

But while these therapies show promise, the process is very intensive. The lymphodepleting regimen increases the risk for infection and patients are commonly hospitalized for a week or more following infusion for toxicity monitoring. Serious adverse events such as cytokine release syndrome (CRS) can occur days to weeks after CAR T-cell infusion. In the five-patient case series reported in 2022, patients were hospitalized for 10 days following treatment.

The patient with antisynthetase syndrome, as well as three of five patients in the SLE case series study experienced mild CRS following infusion. Patients are also at a high risk for infection, as the engineered T cells target all B cells, not just the autoreactive immune cells.

The inability to differentiate between disease-causing and protective immune cells is an issue for all currently available drugs treating autoimmune disease, Dr. Konig said. But scientists are already working on how to make these potent cellular therapies safer and more precise.
 

Alternatives to standard CAR T-cell therapies

Engineering T cells with RNA is a new approach to limit the side effects and toxicity of CAR T-cell therapy, said Chris Jewell, PhD, the chief scientific officer at Cartesian Therapeutics, a biotechnology company based in Gaithersburg, Md. The company’s RNA CAR T-cell (rCAR-T) therapy – called DESCARTES-08 – is in phase 2 clinical trials for treatment of myasthenia gravis. Once these rCAR-T cells are infused in patients, as they divide, the RNAnaturally decays, he explained, meaning that after a certain point, the CAR is no longer expressed.

Cartesian Therapeutics

DESCARTES-08 targets B-cell maturation antigen (BCMA), which is primarily expressed on plasma cells, rather than all B cells, Dr. Jewell said.

“Targeting BCMA, we actually have a more selective profile,” he explained. “We are targeting the cells primarily responsible for the pathogenicity; many plasma cells – such as long-lived plasma cells – also take a long time to repopulate.”

This therapy also does not require lymphodepletion prior to infusion and can be done in an outpatient setting. The therapy is given in multiple infusions, once per week.

In the most recent clinical trial, patients with myasthenia gravis received six infusions over 6 weeks and experienced notable decreases in myasthenia gravis severity scale at up to 9 months of follow-up.

Abata Therapeutics

While standard CAR T-cell therapies under clinical investigational up to now all use effector T cells, regulatory T cells (Tregs) can also be engineered to target autoimmune disease. Abata Therapeutics, based in Boston, is using this approach for therapies for progressive multiple sclerosis and type 1 diabetes. These engineered Tregs express a T-cell receptor (TCR) that recognizes tissue-specific antigens and suppress inflammation at the site of the disease. “Treg-based cell therapies are really harnessing the natural power of regulatory cells to reset immune tolerance and recalibrate the immune system,” said their chief medical officer, Leonard Dragone, MD, PhD.

These therapies are derived from terminally differentiated cells that have limited capacity to produce pro-inflammatory cytokines including interleukin-2 or interferon gamma, Dr. Dragone explained. “CRS is difficult to envision from engineered Treg products and hasn’t been observed in any clinical experience with polyclonal Tregs,” he said.

This approach also does not require lymphodepletion prior to treatment. The company’s Treg cellular therapy for progressive MS is currently in investigational new drug-enabling studies, and they aim to dose their first patients in 2024.
 

Precision immunotherapy

For B-cell driven autoimmune diseases where the autoantibody is known, researchers have begun to re-engineer T cells to recognize only autoreactive B cells. While CD19 CAR T cells act more like a sledgehammer, these precision cellular immunotherapies are “like a razor’s strike,” Dr. June said.

University of Pennsylvania

“The chimeric autoantibody receptor (CAAR) approach targets autoantibodies that are expressed only on the surface of autoimmune B cells and are not expressed on normal B cells, which ideally should lead to precision targeting of just the cells that cause autoimmune disease,” explained Aimee Payne, MD, PhD, professor of dermatology and director of the Penn Clinical Autoimmunity Center of Excellence at the University of Pennsylvania, Philadelphia.

She and her research team used this approach to develop a treatment for mucosal pemphigus vulgaris, an autoimmune blistering disease of mucous membranes driven by autoantibodies against desmoglein 3.

“The current standard of care for pemphigus is to treat with steroids and rituximab, an infusion therapy that results in global, but temporary, B-cell depletion,” she said. “By expressing desmoglein 3 (DSG3) on the surface of the CAAR T-cell therapy, we target just the anti-DSG3 B cells that cause disease in mucosal pemphigus vulgaris and spare the healthy B cells.”

The therapy – called DSG3-CAART – is being developed by Cabaletta Bio and is now in phase 1 clinical trials. The approach is also being investigated to treat certain types of myasthenia gravis and membranous nephropathy.

Dr. Konig’s lab at Johns Hopkins developed and is now exploring a new precision cellular immunotherapy approach, chimeric autoantigen-T cell receptor (CATCR) T-cell therapy, to treat antiphospholipid syndrome, which is in preclinical stages. In this approach, Dr. Konig and his team are “re-engineering the natural T-cell receptor to selectively kill disease-causing B cells that drive antiphospholipid syndrome,” he explained.

He anticipates the CD19 CAR T-cell therapies currently in clinical trials will help to pave the way for this new generation of precision cellular therapies. The ultimate goal of these therapies, he said, is to uncouple therapeutic potency from infection risk.

“That’s really the holy grail in the treatment of autoimmune diseases. It’s tantalizingly close, but we’re not there yet.”

Dr. June is an inventor on patents and/or patent applications licensed to Novartis Institutes of Biomedical Research and receives license revenue from such licenses. Dr. June is a scientific founder of Tmunity Therapeutics and Capstan Therapeutics and is a member of the scientific advisory boards of AC Immune SA, Alaunos, BlueSphere Bio, Cabaletta, Carisma, Cartography Biosciences, Cellares, Celldex, Decheng Capital, Poseida, Verismo, and WIRB-Copernicus Group. Dr. Konig is a consultant for argenx and Revel and is listed as inventor for patent applications filed by John Hopkins University. Dr. Payne holds equity, grants, payments, and patent licensing from Cabaletta Bio and consults for Janssen.

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

A revolutionary treatment for cancers may also be able to treat and reset the immune system to provide long-term remission or possibly even cure certain autoimmune diseases.

Chimeric antigen receptor (CAR) T-cell therapy has offered a novel approach to treating hematologic cancers since 2017, but there are early signs that these cellular immunotherapies could be repurposed for B-cell mediated autoimmune diseases.

In September of last year, researchers in Germany reported that five patients with refractory systemic lupus erythematosus (SLE) treated with CAR T-cell therapy all achieved drug-free remission. At the time of publication, no patients had relapsed for up to 17 months after treatment. The authors described seroconversion of antinuclear antibodies in two patients with the longest follow-up, “indicating that abrogation of autoimmune B-cell clones may lead to a more widespread correction of autoimmunity,” the researchers write.

In another case study published in June, researchers used CD-19 targeted CAR-T cells to treat a 41-year-old man with refractory antisynthetase syndrome with progressive myositis and interstitial lung disease. Six months after treatment, there were no signs of myositis on MRI and a chest CT scan showed full regression of alveolitis.

John Hopkins Medicine

Since then, two biotechnology companies – Cabaletta Bio in Philadelphia and Kyverna Therapeutics in Emeryville, Calif. – have already been granted fast-track designations from the U.S. Food and Drug Administration for CAR T-cell therapy for SLE and lupus nephritis. Bristol-Myers Squibb is also conducting a phase 1 trial in patients with severe, refractory SLE. Several biotechnology companies and hospitals in China are also conducting clinical trials for SLE. But this is only the tip of the iceberg regarding cellular therapies for autoimmune disease, said Max Konig, MD, PhD, an assistant professor of medicine in the division of rheumatology at Johns Hopkins University, Baltimore.

“It’s an incredibly exciting time. It’s unprecedented in the history of autoimmunity,” he noted.
 

A ‘reboot’ for the immune system

B-cell targeted therapies have been around since the early 2000s with drugs like rituximab, a monoclonal antibody medication that targets CD20, an antigen expressed on the surface of B cells. The CAR T cells currently available target another surface antigen, CD19, and are a much more potent therapy. Both are effective at depleting B cells in blood, but these engineered CD19-targeted T cells can reach B cells sitting in tissues in a way that antibody therapies cannot, Dr. Konig explained.

“If you have a patient with myositis, for example, where autoreactive B cells are sitting in the inflamed muscle, or a patient with rheumatoid arthritis, where you have disease-relevant B cells in hard-to-reach tissues like the synovium, those cells are much harder to deplete with an antibody, compared to a T cell that evolved to surveil and effectively kill in all tissues,” he explained.

In this process, T cells are collected from patients via leukapheresis and then re-engineered to express chimeric antigen receptors. A few days before these modified T cells are infused back into the patient, the patients are given a low-dose chemotherapy (lymphodepletion) regimen to help increase the effectiveness of the therapy. The one-time infusion is generally given on an inpatient basis, and patients are then monitored in hospital for side effects.

Once B cells are depleted, disease symptoms improve. But in the case studies published to date, once B cells re-emerge, they are naïve and no longer producing autoreactive B cells.
 

“Maybe it’s like a tabula rasa: You wipe [the B cells] out and start with a clean slate. Then, the immune system reboots, and now it’s working, whereas before it was messed up,” said Carl June, MD, who directs the Center for Cellular Immunotherapies at the at the University of Pennsylvania, Philadelphia. Dr. June and his research team led the development of CAR T-cell therapies for blood cancers.

The findings suggest that autoantibodies “might not be hardwired into the immune system,” he said.

But Dr. Konig stressed that we are still in the early days of clinical trials, and more research is necessary to understand the safety and efficacy of these therapies.

“There’s an incredible buzz around CAR T cells at the moment in rheumatology, which is great because I think that’s where the future is,” he said. “But we still need to learn how to appropriately apply these therapies in randomized, controlled trials.”

So far, the evidence behind CD19 CAR T-cell therapies in autoimmune disease is from case studies and phase 1 trials in a very small number of selected patients. (The upcoming Cabaletta and Kyverna trials in lupus will also be small, consisting of 12 patients each.)
 

Risks of intensive therapy

But while these therapies show promise, the process is very intensive. The lymphodepleting regimen increases the risk for infection and patients are commonly hospitalized for a week or more following infusion for toxicity monitoring. Serious adverse events such as cytokine release syndrome (CRS) can occur days to weeks after CAR T-cell infusion. In the five-patient case series reported in 2022, patients were hospitalized for 10 days following treatment.

The patient with antisynthetase syndrome, as well as three of five patients in the SLE case series study experienced mild CRS following infusion. Patients are also at a high risk for infection, as the engineered T cells target all B cells, not just the autoreactive immune cells.

The inability to differentiate between disease-causing and protective immune cells is an issue for all currently available drugs treating autoimmune disease, Dr. Konig said. But scientists are already working on how to make these potent cellular therapies safer and more precise.
 

Alternatives to standard CAR T-cell therapies

Engineering T cells with RNA is a new approach to limit the side effects and toxicity of CAR T-cell therapy, said Chris Jewell, PhD, the chief scientific officer at Cartesian Therapeutics, a biotechnology company based in Gaithersburg, Md. The company’s RNA CAR T-cell (rCAR-T) therapy – called DESCARTES-08 – is in phase 2 clinical trials for treatment of myasthenia gravis. Once these rCAR-T cells are infused in patients, as they divide, the RNAnaturally decays, he explained, meaning that after a certain point, the CAR is no longer expressed.

Cartesian Therapeutics

DESCARTES-08 targets B-cell maturation antigen (BCMA), which is primarily expressed on plasma cells, rather than all B cells, Dr. Jewell said.

“Targeting BCMA, we actually have a more selective profile,” he explained. “We are targeting the cells primarily responsible for the pathogenicity; many plasma cells – such as long-lived plasma cells – also take a long time to repopulate.”

This therapy also does not require lymphodepletion prior to infusion and can be done in an outpatient setting. The therapy is given in multiple infusions, once per week.

In the most recent clinical trial, patients with myasthenia gravis received six infusions over 6 weeks and experienced notable decreases in myasthenia gravis severity scale at up to 9 months of follow-up.

Abata Therapeutics

While standard CAR T-cell therapies under clinical investigational up to now all use effector T cells, regulatory T cells (Tregs) can also be engineered to target autoimmune disease. Abata Therapeutics, based in Boston, is using this approach for therapies for progressive multiple sclerosis and type 1 diabetes. These engineered Tregs express a T-cell receptor (TCR) that recognizes tissue-specific antigens and suppress inflammation at the site of the disease. “Treg-based cell therapies are really harnessing the natural power of regulatory cells to reset immune tolerance and recalibrate the immune system,” said their chief medical officer, Leonard Dragone, MD, PhD.

These therapies are derived from terminally differentiated cells that have limited capacity to produce pro-inflammatory cytokines including interleukin-2 or interferon gamma, Dr. Dragone explained. “CRS is difficult to envision from engineered Treg products and hasn’t been observed in any clinical experience with polyclonal Tregs,” he said.

This approach also does not require lymphodepletion prior to treatment. The company’s Treg cellular therapy for progressive MS is currently in investigational new drug-enabling studies, and they aim to dose their first patients in 2024.
 

Precision immunotherapy

For B-cell driven autoimmune diseases where the autoantibody is known, researchers have begun to re-engineer T cells to recognize only autoreactive B cells. While CD19 CAR T cells act more like a sledgehammer, these precision cellular immunotherapies are “like a razor’s strike,” Dr. June said.

University of Pennsylvania

“The chimeric autoantibody receptor (CAAR) approach targets autoantibodies that are expressed only on the surface of autoimmune B cells and are not expressed on normal B cells, which ideally should lead to precision targeting of just the cells that cause autoimmune disease,” explained Aimee Payne, MD, PhD, professor of dermatology and director of the Penn Clinical Autoimmunity Center of Excellence at the University of Pennsylvania, Philadelphia.

She and her research team used this approach to develop a treatment for mucosal pemphigus vulgaris, an autoimmune blistering disease of mucous membranes driven by autoantibodies against desmoglein 3.

“The current standard of care for pemphigus is to treat with steroids and rituximab, an infusion therapy that results in global, but temporary, B-cell depletion,” she said. “By expressing desmoglein 3 (DSG3) on the surface of the CAAR T-cell therapy, we target just the anti-DSG3 B cells that cause disease in mucosal pemphigus vulgaris and spare the healthy B cells.”

The therapy – called DSG3-CAART – is being developed by Cabaletta Bio and is now in phase 1 clinical trials. The approach is also being investigated to treat certain types of myasthenia gravis and membranous nephropathy.

Dr. Konig’s lab at Johns Hopkins developed and is now exploring a new precision cellular immunotherapy approach, chimeric autoantigen-T cell receptor (CATCR) T-cell therapy, to treat antiphospholipid syndrome, which is in preclinical stages. In this approach, Dr. Konig and his team are “re-engineering the natural T-cell receptor to selectively kill disease-causing B cells that drive antiphospholipid syndrome,” he explained.

He anticipates the CD19 CAR T-cell therapies currently in clinical trials will help to pave the way for this new generation of precision cellular therapies. The ultimate goal of these therapies, he said, is to uncouple therapeutic potency from infection risk.

“That’s really the holy grail in the treatment of autoimmune diseases. It’s tantalizingly close, but we’re not there yet.”

Dr. June is an inventor on patents and/or patent applications licensed to Novartis Institutes of Biomedical Research and receives license revenue from such licenses. Dr. June is a scientific founder of Tmunity Therapeutics and Capstan Therapeutics and is a member of the scientific advisory boards of AC Immune SA, Alaunos, BlueSphere Bio, Cabaletta, Carisma, Cartography Biosciences, Cellares, Celldex, Decheng Capital, Poseida, Verismo, and WIRB-Copernicus Group. Dr. Konig is a consultant for argenx and Revel and is listed as inventor for patent applications filed by John Hopkins University. Dr. Payne holds equity, grants, payments, and patent licensing from Cabaletta Bio and consults for Janssen.

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

A revolutionary treatment for cancers may also be able to treat and reset the immune system to provide long-term remission or possibly even cure certain autoimmune diseases.

Chimeric antigen receptor (CAR) T-cell therapy has offered a novel approach to treating hematologic cancers since 2017, but there are early signs that these cellular immunotherapies could be repurposed for B-cell mediated autoimmune diseases.

In September of last year, researchers in Germany reported that five patients with refractory systemic lupus erythematosus (SLE) treated with CAR T-cell therapy all achieved drug-free remission. At the time of publication, no patients had relapsed for up to 17 months after treatment. The authors described seroconversion of antinuclear antibodies in two patients with the longest follow-up, “indicating that abrogation of autoimmune B-cell clones may lead to a more widespread correction of autoimmunity,” the researchers write.

In another case study published in June, researchers used CD-19 targeted CAR-T cells to treat a 41-year-old man with refractory antisynthetase syndrome with progressive myositis and interstitial lung disease. Six months after treatment, there were no signs of myositis on MRI and a chest CT scan showed full regression of alveolitis.

John Hopkins Medicine

Since then, two biotechnology companies – Cabaletta Bio in Philadelphia and Kyverna Therapeutics in Emeryville, Calif. – have already been granted fast-track designations from the U.S. Food and Drug Administration for CAR T-cell therapy for SLE and lupus nephritis. Bristol-Myers Squibb is also conducting a phase 1 trial in patients with severe, refractory SLE. Several biotechnology companies and hospitals in China are also conducting clinical trials for SLE. But this is only the tip of the iceberg regarding cellular therapies for autoimmune disease, said Max Konig, MD, PhD, an assistant professor of medicine in the division of rheumatology at Johns Hopkins University, Baltimore.

“It’s an incredibly exciting time. It’s unprecedented in the history of autoimmunity,” he noted.
 

A ‘reboot’ for the immune system

B-cell targeted therapies have been around since the early 2000s with drugs like rituximab, a monoclonal antibody medication that targets CD20, an antigen expressed on the surface of B cells. The CAR T cells currently available target another surface antigen, CD19, and are a much more potent therapy. Both are effective at depleting B cells in blood, but these engineered CD19-targeted T cells can reach B cells sitting in tissues in a way that antibody therapies cannot, Dr. Konig explained.

“If you have a patient with myositis, for example, where autoreactive B cells are sitting in the inflamed muscle, or a patient with rheumatoid arthritis, where you have disease-relevant B cells in hard-to-reach tissues like the synovium, those cells are much harder to deplete with an antibody, compared to a T cell that evolved to surveil and effectively kill in all tissues,” he explained.

In this process, T cells are collected from patients via leukapheresis and then re-engineered to express chimeric antigen receptors. A few days before these modified T cells are infused back into the patient, the patients are given a low-dose chemotherapy (lymphodepletion) regimen to help increase the effectiveness of the therapy. The one-time infusion is generally given on an inpatient basis, and patients are then monitored in hospital for side effects.

Once B cells are depleted, disease symptoms improve. But in the case studies published to date, once B cells re-emerge, they are naïve and no longer producing autoreactive B cells.
 

“Maybe it’s like a tabula rasa: You wipe [the B cells] out and start with a clean slate. Then, the immune system reboots, and now it’s working, whereas before it was messed up,” said Carl June, MD, who directs the Center for Cellular Immunotherapies at the at the University of Pennsylvania, Philadelphia. Dr. June and his research team led the development of CAR T-cell therapies for blood cancers.

The findings suggest that autoantibodies “might not be hardwired into the immune system,” he said.

But Dr. Konig stressed that we are still in the early days of clinical trials, and more research is necessary to understand the safety and efficacy of these therapies.

“There’s an incredible buzz around CAR T cells at the moment in rheumatology, which is great because I think that’s where the future is,” he said. “But we still need to learn how to appropriately apply these therapies in randomized, controlled trials.”

So far, the evidence behind CD19 CAR T-cell therapies in autoimmune disease is from case studies and phase 1 trials in a very small number of selected patients. (The upcoming Cabaletta and Kyverna trials in lupus will also be small, consisting of 12 patients each.)
 

Risks of intensive therapy

But while these therapies show promise, the process is very intensive. The lymphodepleting regimen increases the risk for infection and patients are commonly hospitalized for a week or more following infusion for toxicity monitoring. Serious adverse events such as cytokine release syndrome (CRS) can occur days to weeks after CAR T-cell infusion. In the five-patient case series reported in 2022, patients were hospitalized for 10 days following treatment.

The patient with antisynthetase syndrome, as well as three of five patients in the SLE case series study experienced mild CRS following infusion. Patients are also at a high risk for infection, as the engineered T cells target all B cells, not just the autoreactive immune cells.

The inability to differentiate between disease-causing and protective immune cells is an issue for all currently available drugs treating autoimmune disease, Dr. Konig said. But scientists are already working on how to make these potent cellular therapies safer and more precise.
 

Alternatives to standard CAR T-cell therapies

Engineering T cells with RNA is a new approach to limit the side effects and toxicity of CAR T-cell therapy, said Chris Jewell, PhD, the chief scientific officer at Cartesian Therapeutics, a biotechnology company based in Gaithersburg, Md. The company’s RNA CAR T-cell (rCAR-T) therapy – called DESCARTES-08 – is in phase 2 clinical trials for treatment of myasthenia gravis. Once these rCAR-T cells are infused in patients, as they divide, the RNAnaturally decays, he explained, meaning that after a certain point, the CAR is no longer expressed.

Cartesian Therapeutics

DESCARTES-08 targets B-cell maturation antigen (BCMA), which is primarily expressed on plasma cells, rather than all B cells, Dr. Jewell said.

“Targeting BCMA, we actually have a more selective profile,” he explained. “We are targeting the cells primarily responsible for the pathogenicity; many plasma cells – such as long-lived plasma cells – also take a long time to repopulate.”

This therapy also does not require lymphodepletion prior to infusion and can be done in an outpatient setting. The therapy is given in multiple infusions, once per week.

In the most recent clinical trial, patients with myasthenia gravis received six infusions over 6 weeks and experienced notable decreases in myasthenia gravis severity scale at up to 9 months of follow-up.

Abata Therapeutics

While standard CAR T-cell therapies under clinical investigational up to now all use effector T cells, regulatory T cells (Tregs) can also be engineered to target autoimmune disease. Abata Therapeutics, based in Boston, is using this approach for therapies for progressive multiple sclerosis and type 1 diabetes. These engineered Tregs express a T-cell receptor (TCR) that recognizes tissue-specific antigens and suppress inflammation at the site of the disease. “Treg-based cell therapies are really harnessing the natural power of regulatory cells to reset immune tolerance and recalibrate the immune system,” said their chief medical officer, Leonard Dragone, MD, PhD.

These therapies are derived from terminally differentiated cells that have limited capacity to produce pro-inflammatory cytokines including interleukin-2 or interferon gamma, Dr. Dragone explained. “CRS is difficult to envision from engineered Treg products and hasn’t been observed in any clinical experience with polyclonal Tregs,” he said.

This approach also does not require lymphodepletion prior to treatment. The company’s Treg cellular therapy for progressive MS is currently in investigational new drug-enabling studies, and they aim to dose their first patients in 2024.
 

Precision immunotherapy

For B-cell driven autoimmune diseases where the autoantibody is known, researchers have begun to re-engineer T cells to recognize only autoreactive B cells. While CD19 CAR T cells act more like a sledgehammer, these precision cellular immunotherapies are “like a razor’s strike,” Dr. June said.

University of Pennsylvania

“The chimeric autoantibody receptor (CAAR) approach targets autoantibodies that are expressed only on the surface of autoimmune B cells and are not expressed on normal B cells, which ideally should lead to precision targeting of just the cells that cause autoimmune disease,” explained Aimee Payne, MD, PhD, professor of dermatology and director of the Penn Clinical Autoimmunity Center of Excellence at the University of Pennsylvania, Philadelphia.

She and her research team used this approach to develop a treatment for mucosal pemphigus vulgaris, an autoimmune blistering disease of mucous membranes driven by autoantibodies against desmoglein 3.

“The current standard of care for pemphigus is to treat with steroids and rituximab, an infusion therapy that results in global, but temporary, B-cell depletion,” she said. “By expressing desmoglein 3 (DSG3) on the surface of the CAAR T-cell therapy, we target just the anti-DSG3 B cells that cause disease in mucosal pemphigus vulgaris and spare the healthy B cells.”

The therapy – called DSG3-CAART – is being developed by Cabaletta Bio and is now in phase 1 clinical trials. The approach is also being investigated to treat certain types of myasthenia gravis and membranous nephropathy.

Dr. Konig’s lab at Johns Hopkins developed and is now exploring a new precision cellular immunotherapy approach, chimeric autoantigen-T cell receptor (CATCR) T-cell therapy, to treat antiphospholipid syndrome, which is in preclinical stages. In this approach, Dr. Konig and his team are “re-engineering the natural T-cell receptor to selectively kill disease-causing B cells that drive antiphospholipid syndrome,” he explained.

He anticipates the CD19 CAR T-cell therapies currently in clinical trials will help to pave the way for this new generation of precision cellular therapies. The ultimate goal of these therapies, he said, is to uncouple therapeutic potency from infection risk.

“That’s really the holy grail in the treatment of autoimmune diseases. It’s tantalizingly close, but we’re not there yet.”

Dr. June is an inventor on patents and/or patent applications licensed to Novartis Institutes of Biomedical Research and receives license revenue from such licenses. Dr. June is a scientific founder of Tmunity Therapeutics and Capstan Therapeutics and is a member of the scientific advisory boards of AC Immune SA, Alaunos, BlueSphere Bio, Cabaletta, Carisma, Cartography Biosciences, Cellares, Celldex, Decheng Capital, Poseida, Verismo, and WIRB-Copernicus Group. Dr. Konig is a consultant for argenx and Revel and is listed as inventor for patent applications filed by John Hopkins University. Dr. Payne holds equity, grants, payments, and patent licensing from Cabaletta Bio and consults for Janssen.

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

SAN DIEGO – While mechanical subcision of fat septa with a scalpel or a large bore needle is a tried-and-true treatment for cellulite, other technologies have emerged as alternatives.

A noninvasive treatment, rapid acoustic pulse (RAP) technology (RESONIC), was cleared by the Food and Drug Administration in 2021 for short-term improvement in the appearance of cellulite. The device emits rapid acoustic pulses (shock waves) that are transmitted through the skin to rupture or shear the fibrotic septa; release of the septa results in the smoothing of skin dimples, Arisa E. Ortiz, MD, director of laser and cosmetic dermatology at the University of California, San Diego, said at the annual Masters of Aesthetics Symposium. RAP, however, was “taken off the market temporarily to refine the design.”

Dr. Arisa E. Ortiz

According to Dr. Ortiz, RAP’s repetition rate and short rise time provides microscopic mechanical disruption to the targeted cellular level structures and vacuoles, while high peak pressure and the fast repetition rate exploit the viscoelastic nature of tissue. Compressed pulses from electronic filtering and the reflector shape eliminate cavitation, heat, and pain. Researchers have postulated that the procedure stimulates collagenesis and angiogenesis.

“There’s no heat to this; it just uses sound,” Dr. Ortiz explained. “It’s also time dependent. The longer you do the treatment, the more disruption of the septa you see. The procedure takes 20-30 minutes. Unlike other treatments, it’s not just for discreet dimples. You can treat entire areas like the buttock or posterior leg,” said Dr. Ortiz, who did not use the RAP device in her practice.

Another device, targeted verifiable subcision (TVS, marketed as Avéli), is FDA cleared for temporary reduction in the appearance of cellulite in the buttock and thigh areas of adult women. “But studies show lasting results, at least through a year,” Dr. Ortiz said. The device features a light-guided probe and a hook. The light enables clinicians to navigate under the skin, while the hook releases a tiny blade that severs the septa. “Once you find the septa, then you activate the blade and release the septa. You go right to left because the direction of the blade is on the left of the probe. Then you go back to verify that you got everything that was creating that dimple.”

Previous devices, she said, would “blindly shear the area, so you would find the dimple and blindly cut, so there was no way to verify that you got the target dimple. The results were sometimes mediocre because you didn’t really know if you effectively treated the area.”

Iuliia Mikhalitskaia/Getty Images

She emphasized that TVS is only useful for discreet dimples. “Many patients who come in asking for cellulite treatment have a lot of laxity and rippled texture,” said Dr. Ortiz, who is also president-elect of the American Society for Laser Medicine and Surgery. “This is not going to be appropriate for those cases. Setting expectations is important. If patients have laxity and discreet dimples and it’s just the dimples that bother them, that’s fine. They just need to understand the difference,” she said, noting that this is “safe for all skin types.”

Tumescent anesthesia is used to control pain during the procedure. The most common adverse events are bruising and soreness. Results from a pivotal trial showed that clinically significant improvements in the primary endpoint, Cellulite Severity Scale scores, were sustained 1 year after treatment. “Hemosiderin staining can occur, but it eventually dissipates on its own,” Dr. Ortiz added. “You can use laser to speed up healing but sometimes that can make it worse, so you want to be careful with that. Most of the time I have patients wait it out; it does go away on its own.”

She noted that the development of RAP and TVS have helped clinicians better understand the makeup of septa. “We used to think of septa as singular bands that are vertically oriented in cellulite, but what we’ve realized is that it’s more like a network of septa,” she said.

Another noninvasive technology, synchronous parallel ultrasound beam technology from Sofwave (marketed as SUPERB), was FDA cleared in December 2022 for the short-term improvement in the appearance of cellulite. The device has seven parallel beam transducers that increase tissue temperatures of the treatment area to 60-70° C, inducing collagen remodeling and collagen denaturation, she said.

In the pivotal study of 68 women, two blinded reviewers reported an 89% improvement rate for both cellulite and skin laxity, after two treatments 2-4 weeks apart, according to data she presented at the meeting. The mean pain score during treatment was 4.55 on a scale of 1-10. No safety issues were observed and immediate responses were limited to erythema and edema.

Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies, including receipt of speaker fees and honoraria from Sofwave. She is also cochair of MOAS.

SAN DIEGO – While mechanical subcision of fat septa with a scalpel or a large bore needle is a tried-and-true treatment for cellulite, other technologies have emerged as alternatives.

A noninvasive treatment, rapid acoustic pulse (RAP) technology (RESONIC), was cleared by the Food and Drug Administration in 2021 for short-term improvement in the appearance of cellulite. The device emits rapid acoustic pulses (shock waves) that are transmitted through the skin to rupture or shear the fibrotic septa; release of the septa results in the smoothing of skin dimples, Arisa E. Ortiz, MD, director of laser and cosmetic dermatology at the University of California, San Diego, said at the annual Masters of Aesthetics Symposium. RAP, however, was “taken off the market temporarily to refine the design.”

Dr. Arisa E. Ortiz

According to Dr. Ortiz, RAP’s repetition rate and short rise time provides microscopic mechanical disruption to the targeted cellular level structures and vacuoles, while high peak pressure and the fast repetition rate exploit the viscoelastic nature of tissue. Compressed pulses from electronic filtering and the reflector shape eliminate cavitation, heat, and pain. Researchers have postulated that the procedure stimulates collagenesis and angiogenesis.

“There’s no heat to this; it just uses sound,” Dr. Ortiz explained. “It’s also time dependent. The longer you do the treatment, the more disruption of the septa you see. The procedure takes 20-30 minutes. Unlike other treatments, it’s not just for discreet dimples. You can treat entire areas like the buttock or posterior leg,” said Dr. Ortiz, who did not use the RAP device in her practice.

Another device, targeted verifiable subcision (TVS, marketed as Avéli), is FDA cleared for temporary reduction in the appearance of cellulite in the buttock and thigh areas of adult women. “But studies show lasting results, at least through a year,” Dr. Ortiz said. The device features a light-guided probe and a hook. The light enables clinicians to navigate under the skin, while the hook releases a tiny blade that severs the septa. “Once you find the septa, then you activate the blade and release the septa. You go right to left because the direction of the blade is on the left of the probe. Then you go back to verify that you got everything that was creating that dimple.”

Previous devices, she said, would “blindly shear the area, so you would find the dimple and blindly cut, so there was no way to verify that you got the target dimple. The results were sometimes mediocre because you didn’t really know if you effectively treated the area.”

Iuliia Mikhalitskaia/Getty Images

She emphasized that TVS is only useful for discreet dimples. “Many patients who come in asking for cellulite treatment have a lot of laxity and rippled texture,” said Dr. Ortiz, who is also president-elect of the American Society for Laser Medicine and Surgery. “This is not going to be appropriate for those cases. Setting expectations is important. If patients have laxity and discreet dimples and it’s just the dimples that bother them, that’s fine. They just need to understand the difference,” she said, noting that this is “safe for all skin types.”

Tumescent anesthesia is used to control pain during the procedure. The most common adverse events are bruising and soreness. Results from a pivotal trial showed that clinically significant improvements in the primary endpoint, Cellulite Severity Scale scores, were sustained 1 year after treatment. “Hemosiderin staining can occur, but it eventually dissipates on its own,” Dr. Ortiz added. “You can use laser to speed up healing but sometimes that can make it worse, so you want to be careful with that. Most of the time I have patients wait it out; it does go away on its own.”

She noted that the development of RAP and TVS have helped clinicians better understand the makeup of septa. “We used to think of septa as singular bands that are vertically oriented in cellulite, but what we’ve realized is that it’s more like a network of septa,” she said.

Another noninvasive technology, synchronous parallel ultrasound beam technology from Sofwave (marketed as SUPERB), was FDA cleared in December 2022 for the short-term improvement in the appearance of cellulite. The device has seven parallel beam transducers that increase tissue temperatures of the treatment area to 60-70° C, inducing collagen remodeling and collagen denaturation, she said.

In the pivotal study of 68 women, two blinded reviewers reported an 89% improvement rate for both cellulite and skin laxity, after two treatments 2-4 weeks apart, according to data she presented at the meeting. The mean pain score during treatment was 4.55 on a scale of 1-10. No safety issues were observed and immediate responses were limited to erythema and edema.

Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies, including receipt of speaker fees and honoraria from Sofwave. She is also cochair of MOAS.

SAN DIEGO – While mechanical subcision of fat septa with a scalpel or a large bore needle is a tried-and-true treatment for cellulite, other technologies have emerged as alternatives.

A noninvasive treatment, rapid acoustic pulse (RAP) technology (RESONIC), was cleared by the Food and Drug Administration in 2021 for short-term improvement in the appearance of cellulite. The device emits rapid acoustic pulses (shock waves) that are transmitted through the skin to rupture or shear the fibrotic septa; release of the septa results in the smoothing of skin dimples, Arisa E. Ortiz, MD, director of laser and cosmetic dermatology at the University of California, San Diego, said at the annual Masters of Aesthetics Symposium. RAP, however, was “taken off the market temporarily to refine the design.”

Dr. Arisa E. Ortiz

According to Dr. Ortiz, RAP’s repetition rate and short rise time provides microscopic mechanical disruption to the targeted cellular level structures and vacuoles, while high peak pressure and the fast repetition rate exploit the viscoelastic nature of tissue. Compressed pulses from electronic filtering and the reflector shape eliminate cavitation, heat, and pain. Researchers have postulated that the procedure stimulates collagenesis and angiogenesis.

“There’s no heat to this; it just uses sound,” Dr. Ortiz explained. “It’s also time dependent. The longer you do the treatment, the more disruption of the septa you see. The procedure takes 20-30 minutes. Unlike other treatments, it’s not just for discreet dimples. You can treat entire areas like the buttock or posterior leg,” said Dr. Ortiz, who did not use the RAP device in her practice.

Another device, targeted verifiable subcision (TVS, marketed as Avéli), is FDA cleared for temporary reduction in the appearance of cellulite in the buttock and thigh areas of adult women. “But studies show lasting results, at least through a year,” Dr. Ortiz said. The device features a light-guided probe and a hook. The light enables clinicians to navigate under the skin, while the hook releases a tiny blade that severs the septa. “Once you find the septa, then you activate the blade and release the septa. You go right to left because the direction of the blade is on the left of the probe. Then you go back to verify that you got everything that was creating that dimple.”

Previous devices, she said, would “blindly shear the area, so you would find the dimple and blindly cut, so there was no way to verify that you got the target dimple. The results were sometimes mediocre because you didn’t really know if you effectively treated the area.”

Iuliia Mikhalitskaia/Getty Images

She emphasized that TVS is only useful for discreet dimples. “Many patients who come in asking for cellulite treatment have a lot of laxity and rippled texture,” said Dr. Ortiz, who is also president-elect of the American Society for Laser Medicine and Surgery. “This is not going to be appropriate for those cases. Setting expectations is important. If patients have laxity and discreet dimples and it’s just the dimples that bother them, that’s fine. They just need to understand the difference,” she said, noting that this is “safe for all skin types.”

Tumescent anesthesia is used to control pain during the procedure. The most common adverse events are bruising and soreness. Results from a pivotal trial showed that clinically significant improvements in the primary endpoint, Cellulite Severity Scale scores, were sustained 1 year after treatment. “Hemosiderin staining can occur, but it eventually dissipates on its own,” Dr. Ortiz added. “You can use laser to speed up healing but sometimes that can make it worse, so you want to be careful with that. Most of the time I have patients wait it out; it does go away on its own.”

She noted that the development of RAP and TVS have helped clinicians better understand the makeup of septa. “We used to think of septa as singular bands that are vertically oriented in cellulite, but what we’ve realized is that it’s more like a network of septa,” she said.

Another noninvasive technology, synchronous parallel ultrasound beam technology from Sofwave (marketed as SUPERB), was FDA cleared in December 2022 for the short-term improvement in the appearance of cellulite. The device has seven parallel beam transducers that increase tissue temperatures of the treatment area to 60-70° C, inducing collagen remodeling and collagen denaturation, she said.

In the pivotal study of 68 women, two blinded reviewers reported an 89% improvement rate for both cellulite and skin laxity, after two treatments 2-4 weeks apart, according to data she presented at the meeting. The mean pain score during treatment was 4.55 on a scale of 1-10. No safety issues were observed and immediate responses were limited to erythema and edema.

Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies, including receipt of speaker fees and honoraria from Sofwave. She is also cochair of MOAS.

Some physicians are frustrated that key information about implantable medical devices rarely makes it into electronic health records, despite a 10-year mandate on manufacturers to label these products with identifiers.

As a result of this siloing of information, patients are not getting the expected benefits of a regulation finalized over a decade ago by the U.S. Food and Drug Administration.

In 2013, the agency ordered companies to include unique device identifiers (UDIs) in plain-text and barcode format on some device labels, starting with implanted devices that are considered life-sustaining. The FDA said that tracking of UDI information would speed detection of complications linked to devices.

But identifiers are rarely on devices. At the time of the regulation creation, the FDA also said it expected this data would be integrated into EHRs. But only a few pioneer organizations such as Duke University and Mercy Health have so far attempted to track any UDI data in an organized way, researchers say.

Richard J. Kovacs, MD, the chief medical officer of the American College of Cardiology, contrasted the lack of useful implementation of UDI data with the speedy transfers of information that happen routinely in other industries. For example, employees of car rental agencies use handheld devices to gather detailed information about the vehicles being returned.

“But if you go to an emergency room with a medical device in your body, no one knows what it is or where it came from or anything about it,” Dr. Kovacs said in an interview.

Many physicians with expertise in device research have pushed for years to have insurers like Medicare require identification information on medical claims.

Even researchers face multiple obstacles in trying to investigate how well UDIs have been incorporated into EHRs and outcomes tied to certain devices.

In August, a Harvard team published a study in JAMA Internal Medicine, attempting to analyze the risks of endovascular aortic repair (EVAR) devices. They reported an 11.6% risk for serious blood leaks with AFX Endovascular AAA System aneurysm devices, more than double the 5.7% risk estimated for competing products. The team selected EVAR devices for the study due in part to their known safety concerns. Endologix, the maker of the devices, declined to comment for this story.

The Harvard team used data from the Veterans Affairs health system, which is considered more well organized than most other health systems. But UDI information was found for only 19 of the 13,941 patients whose records were studied. In those cases, only partial information was included.

The researchers developed natural language processing tools, which they used to scrounge clinical notes for information about which devices patients received.

Using this method isn’t feasible for most clinicians, given that records from independent hospitals might not provide this kind of data and descriptions to search, according to the authors of an editorial accompanying the paper. Those researchers urged Congress to pass a law mandating inclusion of UDIs for all devices on claims forms as a condition for reimbursement by federal health care programs.

Setback for advocates

The movement toward UDI suffered a setback in June.

An influential, but little known federal advisory panel, the National Committee on Vital Health Statistics (NCVHS), opted to not recommend use of this information in claims, saying the FDA should consider the matter further.

Gaining an NCVHS recommendation would have been a win, said Sen. Elizabeth Warren (D-MA), Sen. Charles E. Grassley (R-IA), and Rep. Bill Pascrell Jr. (D-NJ), in a December 2022 letter to the panel.

Including UDI data would let researchers track patients’ interactions with a health system and could be used to establish population-level correlations between a particular device and a long-term outcome or side effect, the lawmakers said.

That view had the support of at least one major maker of devices, Cook Group, which sells products for a variety of specialties, including cardiology.

In a comment to NCVHS, Cook urged for the inclusion identifiers in Medicare claims.

“While some have argued that the UDI is better suited for inclusion in the electronic health records, Cook believes this argument sets up a false choice between the two,” wrote Stephen L. Ferguson, JD, the chairman of Cook’s board. “Inclusion of the UDI in both electronic health records and claims forms will lead to a more robust system of real-world data.”

In contrast, AdvaMed, the trade group for device makers, told the NCVHS that it did not support adding the information to payment claims submissions, instead just supporting the inclusion in EHRs.

Dr. Kovacs of the ACC said one potential drawback to more transparency could be challenges in interpreting reports of complications in certain cases, at least initially. Reports about a flaw or even a suspected flaw in a device might lead patients to become concerned about their implanted devices, potentially registering unfounded complaints.

But this concern can be addressed through using “scientific rigor and safeguards” and is outweighed by the potential safety benefits for patients, Dr. Kovacs said.

Patients should ask health care systems to track and share information about their implanted devices, Dr. Kovacs suggested.

“I feel it would be my right to demand that that device information follows my electronic medical record, so that it’s readily available to anyone who’s taking care of me,” Dr. Kovacs said. “They would know what it is that’s in me, whether it’s a lens in my eye or a prosthesis in my hip or a highly complicated implantable cardiac electronic device.”

The Harvard study was supported by the FDA and National Institutes of Health. Authors of the study reported receiving fees from the FDA, Burroughs Wellcome Fund, and Harvard-MIT Center for Regulatory Science outside the submitted work. No other disclosures were reported. Authors of the editorial reported past and present connections with F-Prime Capital, FDA, Johnson & Johnson, the Medical Devices Innovation Consortium; the Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute; and Arnold Ventures, as well being an expert witness at in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen. Authors of the Viewpoint reported past and present connections with the National Evaluation System for Health Technology Coordinating Center (NESTcc), which is part of the Medical Device Innovation Consortium (MDIC); AIM North America UDI Advisory Committee, Mass General Brigham, Arnold Ventures; the Institute for Clinical and Economic Review California Technology Assessment Forum; Yale University, Johnson & Johnson, FD, Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute of the National Institutes of Health; as well as having been an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against.

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

Some physicians are frustrated that key information about implantable medical devices rarely makes it into electronic health records, despite a 10-year mandate on manufacturers to label these products with identifiers.

As a result of this siloing of information, patients are not getting the expected benefits of a regulation finalized over a decade ago by the U.S. Food and Drug Administration.

In 2013, the agency ordered companies to include unique device identifiers (UDIs) in plain-text and barcode format on some device labels, starting with implanted devices that are considered life-sustaining. The FDA said that tracking of UDI information would speed detection of complications linked to devices.

But identifiers are rarely on devices. At the time of the regulation creation, the FDA also said it expected this data would be integrated into EHRs. But only a few pioneer organizations such as Duke University and Mercy Health have so far attempted to track any UDI data in an organized way, researchers say.

Richard J. Kovacs, MD, the chief medical officer of the American College of Cardiology, contrasted the lack of useful implementation of UDI data with the speedy transfers of information that happen routinely in other industries. For example, employees of car rental agencies use handheld devices to gather detailed information about the vehicles being returned.

“But if you go to an emergency room with a medical device in your body, no one knows what it is or where it came from or anything about it,” Dr. Kovacs said in an interview.

Many physicians with expertise in device research have pushed for years to have insurers like Medicare require identification information on medical claims.

Even researchers face multiple obstacles in trying to investigate how well UDIs have been incorporated into EHRs and outcomes tied to certain devices.

In August, a Harvard team published a study in JAMA Internal Medicine, attempting to analyze the risks of endovascular aortic repair (EVAR) devices. They reported an 11.6% risk for serious blood leaks with AFX Endovascular AAA System aneurysm devices, more than double the 5.7% risk estimated for competing products. The team selected EVAR devices for the study due in part to their known safety concerns. Endologix, the maker of the devices, declined to comment for this story.

The Harvard team used data from the Veterans Affairs health system, which is considered more well organized than most other health systems. But UDI information was found for only 19 of the 13,941 patients whose records were studied. In those cases, only partial information was included.

The researchers developed natural language processing tools, which they used to scrounge clinical notes for information about which devices patients received.

Using this method isn’t feasible for most clinicians, given that records from independent hospitals might not provide this kind of data and descriptions to search, according to the authors of an editorial accompanying the paper. Those researchers urged Congress to pass a law mandating inclusion of UDIs for all devices on claims forms as a condition for reimbursement by federal health care programs.

Setback for advocates

The movement toward UDI suffered a setback in June.

An influential, but little known federal advisory panel, the National Committee on Vital Health Statistics (NCVHS), opted to not recommend use of this information in claims, saying the FDA should consider the matter further.

Gaining an NCVHS recommendation would have been a win, said Sen. Elizabeth Warren (D-MA), Sen. Charles E. Grassley (R-IA), and Rep. Bill Pascrell Jr. (D-NJ), in a December 2022 letter to the panel.

Including UDI data would let researchers track patients’ interactions with a health system and could be used to establish population-level correlations between a particular device and a long-term outcome or side effect, the lawmakers said.

That view had the support of at least one major maker of devices, Cook Group, which sells products for a variety of specialties, including cardiology.

In a comment to NCVHS, Cook urged for the inclusion identifiers in Medicare claims.

“While some have argued that the UDI is better suited for inclusion in the electronic health records, Cook believes this argument sets up a false choice between the two,” wrote Stephen L. Ferguson, JD, the chairman of Cook’s board. “Inclusion of the UDI in both electronic health records and claims forms will lead to a more robust system of real-world data.”

In contrast, AdvaMed, the trade group for device makers, told the NCVHS that it did not support adding the information to payment claims submissions, instead just supporting the inclusion in EHRs.

Dr. Kovacs of the ACC said one potential drawback to more transparency could be challenges in interpreting reports of complications in certain cases, at least initially. Reports about a flaw or even a suspected flaw in a device might lead patients to become concerned about their implanted devices, potentially registering unfounded complaints.

But this concern can be addressed through using “scientific rigor and safeguards” and is outweighed by the potential safety benefits for patients, Dr. Kovacs said.

Patients should ask health care systems to track and share information about their implanted devices, Dr. Kovacs suggested.

“I feel it would be my right to demand that that device information follows my electronic medical record, so that it’s readily available to anyone who’s taking care of me,” Dr. Kovacs said. “They would know what it is that’s in me, whether it’s a lens in my eye or a prosthesis in my hip or a highly complicated implantable cardiac electronic device.”

The Harvard study was supported by the FDA and National Institutes of Health. Authors of the study reported receiving fees from the FDA, Burroughs Wellcome Fund, and Harvard-MIT Center for Regulatory Science outside the submitted work. No other disclosures were reported. Authors of the editorial reported past and present connections with F-Prime Capital, FDA, Johnson & Johnson, the Medical Devices Innovation Consortium; the Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute; and Arnold Ventures, as well being an expert witness at in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen. Authors of the Viewpoint reported past and present connections with the National Evaluation System for Health Technology Coordinating Center (NESTcc), which is part of the Medical Device Innovation Consortium (MDIC); AIM North America UDI Advisory Committee, Mass General Brigham, Arnold Ventures; the Institute for Clinical and Economic Review California Technology Assessment Forum; Yale University, Johnson & Johnson, FD, Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute of the National Institutes of Health; as well as having been an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against.

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

Some physicians are frustrated that key information about implantable medical devices rarely makes it into electronic health records, despite a 10-year mandate on manufacturers to label these products with identifiers.

As a result of this siloing of information, patients are not getting the expected benefits of a regulation finalized over a decade ago by the U.S. Food and Drug Administration.

In 2013, the agency ordered companies to include unique device identifiers (UDIs) in plain-text and barcode format on some device labels, starting with implanted devices that are considered life-sustaining. The FDA said that tracking of UDI information would speed detection of complications linked to devices.

But identifiers are rarely on devices. At the time of the regulation creation, the FDA also said it expected this data would be integrated into EHRs. But only a few pioneer organizations such as Duke University and Mercy Health have so far attempted to track any UDI data in an organized way, researchers say.

Richard J. Kovacs, MD, the chief medical officer of the American College of Cardiology, contrasted the lack of useful implementation of UDI data with the speedy transfers of information that happen routinely in other industries. For example, employees of car rental agencies use handheld devices to gather detailed information about the vehicles being returned.

“But if you go to an emergency room with a medical device in your body, no one knows what it is or where it came from or anything about it,” Dr. Kovacs said in an interview.

Many physicians with expertise in device research have pushed for years to have insurers like Medicare require identification information on medical claims.

Even researchers face multiple obstacles in trying to investigate how well UDIs have been incorporated into EHRs and outcomes tied to certain devices.

In August, a Harvard team published a study in JAMA Internal Medicine, attempting to analyze the risks of endovascular aortic repair (EVAR) devices. They reported an 11.6% risk for serious blood leaks with AFX Endovascular AAA System aneurysm devices, more than double the 5.7% risk estimated for competing products. The team selected EVAR devices for the study due in part to their known safety concerns. Endologix, the maker of the devices, declined to comment for this story.

The Harvard team used data from the Veterans Affairs health system, which is considered more well organized than most other health systems. But UDI information was found for only 19 of the 13,941 patients whose records were studied. In those cases, only partial information was included.

The researchers developed natural language processing tools, which they used to scrounge clinical notes for information about which devices patients received.

Using this method isn’t feasible for most clinicians, given that records from independent hospitals might not provide this kind of data and descriptions to search, according to the authors of an editorial accompanying the paper. Those researchers urged Congress to pass a law mandating inclusion of UDIs for all devices on claims forms as a condition for reimbursement by federal health care programs.

Setback for advocates

The movement toward UDI suffered a setback in June.

An influential, but little known federal advisory panel, the National Committee on Vital Health Statistics (NCVHS), opted to not recommend use of this information in claims, saying the FDA should consider the matter further.

Gaining an NCVHS recommendation would have been a win, said Sen. Elizabeth Warren (D-MA), Sen. Charles E. Grassley (R-IA), and Rep. Bill Pascrell Jr. (D-NJ), in a December 2022 letter to the panel.

Including UDI data would let researchers track patients’ interactions with a health system and could be used to establish population-level correlations between a particular device and a long-term outcome or side effect, the lawmakers said.

That view had the support of at least one major maker of devices, Cook Group, which sells products for a variety of specialties, including cardiology.

In a comment to NCVHS, Cook urged for the inclusion identifiers in Medicare claims.

“While some have argued that the UDI is better suited for inclusion in the electronic health records, Cook believes this argument sets up a false choice between the two,” wrote Stephen L. Ferguson, JD, the chairman of Cook’s board. “Inclusion of the UDI in both electronic health records and claims forms will lead to a more robust system of real-world data.”

In contrast, AdvaMed, the trade group for device makers, told the NCVHS that it did not support adding the information to payment claims submissions, instead just supporting the inclusion in EHRs.

Dr. Kovacs of the ACC said one potential drawback to more transparency could be challenges in interpreting reports of complications in certain cases, at least initially. Reports about a flaw or even a suspected flaw in a device might lead patients to become concerned about their implanted devices, potentially registering unfounded complaints.

But this concern can be addressed through using “scientific rigor and safeguards” and is outweighed by the potential safety benefits for patients, Dr. Kovacs said.

Patients should ask health care systems to track and share information about their implanted devices, Dr. Kovacs suggested.

“I feel it would be my right to demand that that device information follows my electronic medical record, so that it’s readily available to anyone who’s taking care of me,” Dr. Kovacs said. “They would know what it is that’s in me, whether it’s a lens in my eye or a prosthesis in my hip or a highly complicated implantable cardiac electronic device.”

The Harvard study was supported by the FDA and National Institutes of Health. Authors of the study reported receiving fees from the FDA, Burroughs Wellcome Fund, and Harvard-MIT Center for Regulatory Science outside the submitted work. No other disclosures were reported. Authors of the editorial reported past and present connections with F-Prime Capital, FDA, Johnson & Johnson, the Medical Devices Innovation Consortium; the Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute; and Arnold Ventures, as well being an expert witness at in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen. Authors of the Viewpoint reported past and present connections with the National Evaluation System for Health Technology Coordinating Center (NESTcc), which is part of the Medical Device Innovation Consortium (MDIC); AIM North America UDI Advisory Committee, Mass General Brigham, Arnold Ventures; the Institute for Clinical and Economic Review California Technology Assessment Forum; Yale University, Johnson & Johnson, FD, Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute of the National Institutes of Health; as well as having been an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against.

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