Federal Practitioner

Young premenopausal women with early stage hormone receptor (HR)-positive, HER2-negative breast cancer have notable genomic features that may help explain their historically poor outcomes and offer clues about molecular targets for future trials.

Compared with older women with early stage HR-positive breast cancer, women under 40 years of age had significantly higher frequencies of certain mutations, such as GATA3, as well as genomic features associated with a poor prognosis. Notably, the researchers found that women with such poor prognostic features vs. those with none had a significantly worse 8-year distant recurrence-free interval and overall survival.

“We have demonstrated age-related differences in genomic profiles with enrichment of genomic features associated with poor prognosis in these younger premenopausal women compared with older premenopausal and postmenopausal women,” the authors wrote in the study, published in the Annals of Oncology. Importantly, the genomic features highlight “the potential for age-focused treatment strategies.”

Charis Eng, MD, PhD, of the Cleveland Clinic Genomic Medicine Institute, Ohio, noted that the findings are promising but need further validation.

“With time and the appropriate clinical trials in place, I envision that these findings will enable the personalized genomics-driven management of these cancers – not only treatment, but also toward prevention,” said Dr. Eng, who was not involved in the study.

Young premenopausal women, particularly those with HR-positive, luminal breast cancer, are known to have significantly higher recurrence rates and worse survival, compared with older women, but the reasons have remained unclear.

Although previous studies have identified key gene expression signatures linked to worse outcomes in younger patients with breast cancer, there are limited data on this younger patient population, especially by breast cancer subtype. Given that breast cancer treatment strategies are often similar across age groups, such evidence gaps could represent missed opportunities for developing more targeted treatment strategies for this high-risk population of young women.

To further investigate the cancer-specific genetic profiles in younger women, Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre, University of Melbourne, and colleagues turned to data from the pivotal, multicenter Suppression of Ovarian Function Trial (SOFT).

Using next-generation sequencing, Dr. Loi and colleagues evaluated HR-positive, HER2-negative tumors among a subset of 1,276 premenopausal women who were diagnosed with early stage breast cancer. The study employed deep-targeted sequencing for most patients (n = 1,258) as well as whole-exome sequencing in a matched case-control subsample of young women with a median age of 38 years (n = 82).

Compared with women aged 40 and older, those under 40 years of age (n = 359) had significantly higher frequencies of mutations in GATA3 (19% vs. 16%) and copy number-amplifications (47% vs. 26%).

Younger women also had significantly higher features suggestive of homologous recombination deficiency (27% vs. 21% in older women), and a higher proportion of PIK3CA mutations with concurrent copy number-amplifications (23% vs. 11%, respectively), all considered to be poor prognostic features.

In addition, younger women had significantly lower frequencies of certain mutations, including PIK3CA (32% vs. 47%), CDH1 (3% vs. 9%), and MAP3K1 (7% vs. 12%), compared with older women.

Overall, 46% of women had poor prognostic features. These poor prognostic features were observed in 72% of patients under age 35, compared with 54% aged 35-39, and 40% of those 40 and over.

Compared with women without those features, women with poor prognostic features had a lower 8-year distant recurrence-free interval of 84% vs. 94% (hazard ratio, 1.85), and worse 8-year overall survival of 88% vs. 96%, respectively (HR, 2.20). Notably, younger women under age 40 had the poorest outcomes, with an 8-year distant recurrence-free interval rate of 74% vs. 85% in older women, and an 8-year overall survival of 80% vs. 93%, respectively.

How might these results inform potential therapeutics?

Drugs targeting the homologous recombination deficiency pathway are well established, and up to 36% of very young patients in the study showed genomic features of homologous recombination deficiency, the authors noted.

In addition, Dr. Eng explained, there are other Food and Drug Administration–approved treatments that can target the copy number amplified, PIK3CA-mutated tumors, including therapies that target PIK3CA itself, or proteins downstream of it. However, use of such therapies would need “to be tested experimentally, especially since pathway inhibition sometimes may result in rebound signaling to promote tumor growth,” Dr. Eng said.

An important caveat is that patients with germline BRCA1 or BRCA2 mutations may be underrepresented in the SOFT clinical trial, as the trial excluded patients who already had bilateral oophorectomy or planned to within 5 years, the authors noted.

Nevertheless, Dr. Loi said that the study is important because “there are no other datasets as large or with this long follow-up for very young women with breast cancer.”

Furthermore, “the SOFT clinical trial was practice-changing, so using the tumor samples associated with this study is more impactful than smaller cohorts with no outcome data or institutional retrospective cohorts,” she said.

Dr. Eng agreed that the study’s size is an important attribute, allowing the authors to “identify differences that would have been missed in a smaller and more heterogeneous series.”

She added that future research should also include ancestry and racial diversity.

“While young women have higher occurrences of aggressive breast cancers, mortality is twice as likely in young Black women, compared to young White women,” Dr. Eng said.

The study received funding from a Susan G. Komen for the Cure Promise Grant, the National Health and Research Council of Australia, the Breast Cancer Research Foundation, and the National Breast Cancer Foundation of Australia, and support from the family of Judy Eisman in Australia. Dr. Loi and Dr. Eng report no relevant financial disclosures.
 

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

Young premenopausal women with early stage hormone receptor (HR)-positive, HER2-negative breast cancer have notable genomic features that may help explain their historically poor outcomes and offer clues about molecular targets for future trials.

Compared with older women with early stage HR-positive breast cancer, women under 40 years of age had significantly higher frequencies of certain mutations, such as GATA3, as well as genomic features associated with a poor prognosis. Notably, the researchers found that women with such poor prognostic features vs. those with none had a significantly worse 8-year distant recurrence-free interval and overall survival.

“We have demonstrated age-related differences in genomic profiles with enrichment of genomic features associated with poor prognosis in these younger premenopausal women compared with older premenopausal and postmenopausal women,” the authors wrote in the study, published in the Annals of Oncology. Importantly, the genomic features highlight “the potential for age-focused treatment strategies.”

Charis Eng, MD, PhD, of the Cleveland Clinic Genomic Medicine Institute, Ohio, noted that the findings are promising but need further validation.

“With time and the appropriate clinical trials in place, I envision that these findings will enable the personalized genomics-driven management of these cancers – not only treatment, but also toward prevention,” said Dr. Eng, who was not involved in the study.

Young premenopausal women, particularly those with HR-positive, luminal breast cancer, are known to have significantly higher recurrence rates and worse survival, compared with older women, but the reasons have remained unclear.

Although previous studies have identified key gene expression signatures linked to worse outcomes in younger patients with breast cancer, there are limited data on this younger patient population, especially by breast cancer subtype. Given that breast cancer treatment strategies are often similar across age groups, such evidence gaps could represent missed opportunities for developing more targeted treatment strategies for this high-risk population of young women.

To further investigate the cancer-specific genetic profiles in younger women, Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre, University of Melbourne, and colleagues turned to data from the pivotal, multicenter Suppression of Ovarian Function Trial (SOFT).

Using next-generation sequencing, Dr. Loi and colleagues evaluated HR-positive, HER2-negative tumors among a subset of 1,276 premenopausal women who were diagnosed with early stage breast cancer. The study employed deep-targeted sequencing for most patients (n = 1,258) as well as whole-exome sequencing in a matched case-control subsample of young women with a median age of 38 years (n = 82).

Compared with women aged 40 and older, those under 40 years of age (n = 359) had significantly higher frequencies of mutations in GATA3 (19% vs. 16%) and copy number-amplifications (47% vs. 26%).

Younger women also had significantly higher features suggestive of homologous recombination deficiency (27% vs. 21% in older women), and a higher proportion of PIK3CA mutations with concurrent copy number-amplifications (23% vs. 11%, respectively), all considered to be poor prognostic features.

In addition, younger women had significantly lower frequencies of certain mutations, including PIK3CA (32% vs. 47%), CDH1 (3% vs. 9%), and MAP3K1 (7% vs. 12%), compared with older women.

Overall, 46% of women had poor prognostic features. These poor prognostic features were observed in 72% of patients under age 35, compared with 54% aged 35-39, and 40% of those 40 and over.

Compared with women without those features, women with poor prognostic features had a lower 8-year distant recurrence-free interval of 84% vs. 94% (hazard ratio, 1.85), and worse 8-year overall survival of 88% vs. 96%, respectively (HR, 2.20). Notably, younger women under age 40 had the poorest outcomes, with an 8-year distant recurrence-free interval rate of 74% vs. 85% in older women, and an 8-year overall survival of 80% vs. 93%, respectively.

How might these results inform potential therapeutics?

Drugs targeting the homologous recombination deficiency pathway are well established, and up to 36% of very young patients in the study showed genomic features of homologous recombination deficiency, the authors noted.

In addition, Dr. Eng explained, there are other Food and Drug Administration–approved treatments that can target the copy number amplified, PIK3CA-mutated tumors, including therapies that target PIK3CA itself, or proteins downstream of it. However, use of such therapies would need “to be tested experimentally, especially since pathway inhibition sometimes may result in rebound signaling to promote tumor growth,” Dr. Eng said.

An important caveat is that patients with germline BRCA1 or BRCA2 mutations may be underrepresented in the SOFT clinical trial, as the trial excluded patients who already had bilateral oophorectomy or planned to within 5 years, the authors noted.

Nevertheless, Dr. Loi said that the study is important because “there are no other datasets as large or with this long follow-up for very young women with breast cancer.”

Furthermore, “the SOFT clinical trial was practice-changing, so using the tumor samples associated with this study is more impactful than smaller cohorts with no outcome data or institutional retrospective cohorts,” she said.

Dr. Eng agreed that the study’s size is an important attribute, allowing the authors to “identify differences that would have been missed in a smaller and more heterogeneous series.”

She added that future research should also include ancestry and racial diversity.

“While young women have higher occurrences of aggressive breast cancers, mortality is twice as likely in young Black women, compared to young White women,” Dr. Eng said.

The study received funding from a Susan G. Komen for the Cure Promise Grant, the National Health and Research Council of Australia, the Breast Cancer Research Foundation, and the National Breast Cancer Foundation of Australia, and support from the family of Judy Eisman in Australia. Dr. Loi and Dr. Eng report no relevant financial disclosures.
 

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

Young premenopausal women with early stage hormone receptor (HR)-positive, HER2-negative breast cancer have notable genomic features that may help explain their historically poor outcomes and offer clues about molecular targets for future trials.

Compared with older women with early stage HR-positive breast cancer, women under 40 years of age had significantly higher frequencies of certain mutations, such as GATA3, as well as genomic features associated with a poor prognosis. Notably, the researchers found that women with such poor prognostic features vs. those with none had a significantly worse 8-year distant recurrence-free interval and overall survival.

“We have demonstrated age-related differences in genomic profiles with enrichment of genomic features associated with poor prognosis in these younger premenopausal women compared with older premenopausal and postmenopausal women,” the authors wrote in the study, published in the Annals of Oncology. Importantly, the genomic features highlight “the potential for age-focused treatment strategies.”

Charis Eng, MD, PhD, of the Cleveland Clinic Genomic Medicine Institute, Ohio, noted that the findings are promising but need further validation.

“With time and the appropriate clinical trials in place, I envision that these findings will enable the personalized genomics-driven management of these cancers – not only treatment, but also toward prevention,” said Dr. Eng, who was not involved in the study.

Young premenopausal women, particularly those with HR-positive, luminal breast cancer, are known to have significantly higher recurrence rates and worse survival, compared with older women, but the reasons have remained unclear.

Although previous studies have identified key gene expression signatures linked to worse outcomes in younger patients with breast cancer, there are limited data on this younger patient population, especially by breast cancer subtype. Given that breast cancer treatment strategies are often similar across age groups, such evidence gaps could represent missed opportunities for developing more targeted treatment strategies for this high-risk population of young women.

To further investigate the cancer-specific genetic profiles in younger women, Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre, University of Melbourne, and colleagues turned to data from the pivotal, multicenter Suppression of Ovarian Function Trial (SOFT).

Using next-generation sequencing, Dr. Loi and colleagues evaluated HR-positive, HER2-negative tumors among a subset of 1,276 premenopausal women who were diagnosed with early stage breast cancer. The study employed deep-targeted sequencing for most patients (n = 1,258) as well as whole-exome sequencing in a matched case-control subsample of young women with a median age of 38 years (n = 82).

Compared with women aged 40 and older, those under 40 years of age (n = 359) had significantly higher frequencies of mutations in GATA3 (19% vs. 16%) and copy number-amplifications (47% vs. 26%).

Younger women also had significantly higher features suggestive of homologous recombination deficiency (27% vs. 21% in older women), and a higher proportion of PIK3CA mutations with concurrent copy number-amplifications (23% vs. 11%, respectively), all considered to be poor prognostic features.

In addition, younger women had significantly lower frequencies of certain mutations, including PIK3CA (32% vs. 47%), CDH1 (3% vs. 9%), and MAP3K1 (7% vs. 12%), compared with older women.

Overall, 46% of women had poor prognostic features. These poor prognostic features were observed in 72% of patients under age 35, compared with 54% aged 35-39, and 40% of those 40 and over.

Compared with women without those features, women with poor prognostic features had a lower 8-year distant recurrence-free interval of 84% vs. 94% (hazard ratio, 1.85), and worse 8-year overall survival of 88% vs. 96%, respectively (HR, 2.20). Notably, younger women under age 40 had the poorest outcomes, with an 8-year distant recurrence-free interval rate of 74% vs. 85% in older women, and an 8-year overall survival of 80% vs. 93%, respectively.

How might these results inform potential therapeutics?

Drugs targeting the homologous recombination deficiency pathway are well established, and up to 36% of very young patients in the study showed genomic features of homologous recombination deficiency, the authors noted.

In addition, Dr. Eng explained, there are other Food and Drug Administration–approved treatments that can target the copy number amplified, PIK3CA-mutated tumors, including therapies that target PIK3CA itself, or proteins downstream of it. However, use of such therapies would need “to be tested experimentally, especially since pathway inhibition sometimes may result in rebound signaling to promote tumor growth,” Dr. Eng said.

An important caveat is that patients with germline BRCA1 or BRCA2 mutations may be underrepresented in the SOFT clinical trial, as the trial excluded patients who already had bilateral oophorectomy or planned to within 5 years, the authors noted.

Nevertheless, Dr. Loi said that the study is important because “there are no other datasets as large or with this long follow-up for very young women with breast cancer.”

Furthermore, “the SOFT clinical trial was practice-changing, so using the tumor samples associated with this study is more impactful than smaller cohorts with no outcome data or institutional retrospective cohorts,” she said.

Dr. Eng agreed that the study’s size is an important attribute, allowing the authors to “identify differences that would have been missed in a smaller and more heterogeneous series.”

She added that future research should also include ancestry and racial diversity.

“While young women have higher occurrences of aggressive breast cancers, mortality is twice as likely in young Black women, compared to young White women,” Dr. Eng said.

The study received funding from a Susan G. Komen for the Cure Promise Grant, the National Health and Research Council of Australia, the Breast Cancer Research Foundation, and the National Breast Cancer Foundation of Australia, and support from the family of Judy Eisman in Australia. Dr. Loi and Dr. Eng report no relevant financial disclosures.
 

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

“Don’t close the barn door after the horse is gone,” the old proverb goes. In other words, there’s no sense in trying to prevent something when it’s already too late.

In many ways and for many years, this saying has applied to providing local therapies to treat cancers that have metastasized to distant sites. I learned this lesson early on from my mentors and have relayed it to countless patients with advanced cancer over the past several decades.

But a growing body of evidence, alongside promising new therapies, highlights more and more exceptions to this long-held belief. Over my career, I have increasingly learned about the nuances of metastatic disease, specifically that metastasis represents a broad spectrum of indolent to extremely aggressive cancers.

This concept was outlined decades ago for oligometastatic disease and has since been studied in greater depth, and is even being applied in practice. Local therapy for colorectal cancer with limited liver-only metastases is now established as a path to potentially excellent long-term survival. And prospective randomized trials of local therapies for oligometastatic lung cancer or prostate cancer have also demonstrated improvements in clinical outcomes that should lead us to strongly consider integrating local therapy for appropriately selected patients.

In addition, early retrospective studies have provided a proof of principle that patients with solitary brain or adrenal metastases from non–small cell lung cancer (NSCLC) can do exceptionally well and even remain disease-free for many years after definitive local therapy to the primary tumor and oligometastatic disease. For example, a recent press release on the LUNAR trial reported an improvement in overall survival with tumor-treating fields (TTFs), a local therapy, compared with docetaxel as second-line therapy for patients with advanced NSCLC.

That said, the selection process for who receives local therapy remains subjective. In practice, I see patients who fall well outside of conventional oligometastatic parameters but who are directed to local therapy, commonly when systemic therapy is considered futile or prohibitively toxic.

At the same time, however, I also see many patients who would be appropriate candidates for local therapy for oligometastatic disease for whom this strategy is not pursued, perhaps because some oncologists remain dubious about the value of local therapy in this setting. And although we await the full data from the LUNAR trial, I would expect TTFs to face challenges in broad adoption because it is a novel platform with cumbersome practical application, particularly outside of larger centers.

But beyond the potential for TTFs to change management of previously treated advanced NSCLC, I think the findings are more significant because they represent a step, perhaps even a quantum leap, in the role that local therapy could play in improving survival in a broad, unselected population with advanced disease. That is a far more meaningful prospect than conferring benefits in well-selected patients with a narrow subtype of lung cancer. It will be important to determine whether certain subgroups from the LUNAR trial are driving this overall survival benefit.

Local therapy may even have value in the advanced cancer setting beyond oligometastatic disease. That potential is being explored in the SABR-COMET-10 trial, which randomly assigned 159 patients with 4-10 metastatic lesions from various cancers to stereotactic ablative body radiation with standard systemic therapy or the latter alone. With overall survival as the primary endpoint, this study could further revise our understanding of the use of local therapy for treating patients whose cancer biology does not fit the definition of oligometastatic disease.

Does this evolving landscape mean that we were wrong to minimize the role of local therapy?

I don’t think so. The risk/benefit of local therapy today is predicated on two key factors that were absent a few decades ago. First, local therapies such as stereotactic ablative body radiation, minimally invasive surgery, and TTFs now offer disease control with far less attendant toxicity than conventional external beam radiation therapy or open surgery. Second, newer systemic therapies that include targeted therapies and immunotherapy confer remarkably greater disease control for far more patients than does conventional chemotherapy alone.

It is this combination of local therapy’s excellent therapeutic index applied against a background of far better systemic disease control that makes the interplay of local and systemic treatments a newly relevant, open question.

We have yet to see the details of several pivotal trials, but I feel that we should be prepared to question some of the historic dogma in our field to achieve better outcomes not just for selected, narrow subgroups but for a broader population with different types of metastatic cancer.
 

Dr. West is clinical associate professor, department of medical oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He disclosed ties with Ariad/Takeda, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech/Roche, Merck, Pfizer, and Spectrum. A version of this article originally appeared on Medscape.com.

“Don’t close the barn door after the horse is gone,” the old proverb goes. In other words, there’s no sense in trying to prevent something when it’s already too late.

In many ways and for many years, this saying has applied to providing local therapies to treat cancers that have metastasized to distant sites. I learned this lesson early on from my mentors and have relayed it to countless patients with advanced cancer over the past several decades.

But a growing body of evidence, alongside promising new therapies, highlights more and more exceptions to this long-held belief. Over my career, I have increasingly learned about the nuances of metastatic disease, specifically that metastasis represents a broad spectrum of indolent to extremely aggressive cancers.

This concept was outlined decades ago for oligometastatic disease and has since been studied in greater depth, and is even being applied in practice. Local therapy for colorectal cancer with limited liver-only metastases is now established as a path to potentially excellent long-term survival. And prospective randomized trials of local therapies for oligometastatic lung cancer or prostate cancer have also demonstrated improvements in clinical outcomes that should lead us to strongly consider integrating local therapy for appropriately selected patients.

In addition, early retrospective studies have provided a proof of principle that patients with solitary brain or adrenal metastases from non–small cell lung cancer (NSCLC) can do exceptionally well and even remain disease-free for many years after definitive local therapy to the primary tumor and oligometastatic disease. For example, a recent press release on the LUNAR trial reported an improvement in overall survival with tumor-treating fields (TTFs), a local therapy, compared with docetaxel as second-line therapy for patients with advanced NSCLC.

That said, the selection process for who receives local therapy remains subjective. In practice, I see patients who fall well outside of conventional oligometastatic parameters but who are directed to local therapy, commonly when systemic therapy is considered futile or prohibitively toxic.

At the same time, however, I also see many patients who would be appropriate candidates for local therapy for oligometastatic disease for whom this strategy is not pursued, perhaps because some oncologists remain dubious about the value of local therapy in this setting. And although we await the full data from the LUNAR trial, I would expect TTFs to face challenges in broad adoption because it is a novel platform with cumbersome practical application, particularly outside of larger centers.

But beyond the potential for TTFs to change management of previously treated advanced NSCLC, I think the findings are more significant because they represent a step, perhaps even a quantum leap, in the role that local therapy could play in improving survival in a broad, unselected population with advanced disease. That is a far more meaningful prospect than conferring benefits in well-selected patients with a narrow subtype of lung cancer. It will be important to determine whether certain subgroups from the LUNAR trial are driving this overall survival benefit.

Local therapy may even have value in the advanced cancer setting beyond oligometastatic disease. That potential is being explored in the SABR-COMET-10 trial, which randomly assigned 159 patients with 4-10 metastatic lesions from various cancers to stereotactic ablative body radiation with standard systemic therapy or the latter alone. With overall survival as the primary endpoint, this study could further revise our understanding of the use of local therapy for treating patients whose cancer biology does not fit the definition of oligometastatic disease.

Does this evolving landscape mean that we were wrong to minimize the role of local therapy?

I don’t think so. The risk/benefit of local therapy today is predicated on two key factors that were absent a few decades ago. First, local therapies such as stereotactic ablative body radiation, minimally invasive surgery, and TTFs now offer disease control with far less attendant toxicity than conventional external beam radiation therapy or open surgery. Second, newer systemic therapies that include targeted therapies and immunotherapy confer remarkably greater disease control for far more patients than does conventional chemotherapy alone.

It is this combination of local therapy’s excellent therapeutic index applied against a background of far better systemic disease control that makes the interplay of local and systemic treatments a newly relevant, open question.

We have yet to see the details of several pivotal trials, but I feel that we should be prepared to question some of the historic dogma in our field to achieve better outcomes not just for selected, narrow subgroups but for a broader population with different types of metastatic cancer.
 

Dr. West is clinical associate professor, department of medical oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He disclosed ties with Ariad/Takeda, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech/Roche, Merck, Pfizer, and Spectrum. A version of this article originally appeared on Medscape.com.

“Don’t close the barn door after the horse is gone,” the old proverb goes. In other words, there’s no sense in trying to prevent something when it’s already too late.

In many ways and for many years, this saying has applied to providing local therapies to treat cancers that have metastasized to distant sites. I learned this lesson early on from my mentors and have relayed it to countless patients with advanced cancer over the past several decades.

But a growing body of evidence, alongside promising new therapies, highlights more and more exceptions to this long-held belief. Over my career, I have increasingly learned about the nuances of metastatic disease, specifically that metastasis represents a broad spectrum of indolent to extremely aggressive cancers.

This concept was outlined decades ago for oligometastatic disease and has since been studied in greater depth, and is even being applied in practice. Local therapy for colorectal cancer with limited liver-only metastases is now established as a path to potentially excellent long-term survival. And prospective randomized trials of local therapies for oligometastatic lung cancer or prostate cancer have also demonstrated improvements in clinical outcomes that should lead us to strongly consider integrating local therapy for appropriately selected patients.

In addition, early retrospective studies have provided a proof of principle that patients with solitary brain or adrenal metastases from non–small cell lung cancer (NSCLC) can do exceptionally well and even remain disease-free for many years after definitive local therapy to the primary tumor and oligometastatic disease. For example, a recent press release on the LUNAR trial reported an improvement in overall survival with tumor-treating fields (TTFs), a local therapy, compared with docetaxel as second-line therapy for patients with advanced NSCLC.

That said, the selection process for who receives local therapy remains subjective. In practice, I see patients who fall well outside of conventional oligometastatic parameters but who are directed to local therapy, commonly when systemic therapy is considered futile or prohibitively toxic.

At the same time, however, I also see many patients who would be appropriate candidates for local therapy for oligometastatic disease for whom this strategy is not pursued, perhaps because some oncologists remain dubious about the value of local therapy in this setting. And although we await the full data from the LUNAR trial, I would expect TTFs to face challenges in broad adoption because it is a novel platform with cumbersome practical application, particularly outside of larger centers.

But beyond the potential for TTFs to change management of previously treated advanced NSCLC, I think the findings are more significant because they represent a step, perhaps even a quantum leap, in the role that local therapy could play in improving survival in a broad, unselected population with advanced disease. That is a far more meaningful prospect than conferring benefits in well-selected patients with a narrow subtype of lung cancer. It will be important to determine whether certain subgroups from the LUNAR trial are driving this overall survival benefit.

Local therapy may even have value in the advanced cancer setting beyond oligometastatic disease. That potential is being explored in the SABR-COMET-10 trial, which randomly assigned 159 patients with 4-10 metastatic lesions from various cancers to stereotactic ablative body radiation with standard systemic therapy or the latter alone. With overall survival as the primary endpoint, this study could further revise our understanding of the use of local therapy for treating patients whose cancer biology does not fit the definition of oligometastatic disease.

Does this evolving landscape mean that we were wrong to minimize the role of local therapy?

I don’t think so. The risk/benefit of local therapy today is predicated on two key factors that were absent a few decades ago. First, local therapies such as stereotactic ablative body radiation, minimally invasive surgery, and TTFs now offer disease control with far less attendant toxicity than conventional external beam radiation therapy or open surgery. Second, newer systemic therapies that include targeted therapies and immunotherapy confer remarkably greater disease control for far more patients than does conventional chemotherapy alone.

It is this combination of local therapy’s excellent therapeutic index applied against a background of far better systemic disease control that makes the interplay of local and systemic treatments a newly relevant, open question.

We have yet to see the details of several pivotal trials, but I feel that we should be prepared to question some of the historic dogma in our field to achieve better outcomes not just for selected, narrow subgroups but for a broader population with different types of metastatic cancer.
 

Dr. West is clinical associate professor, department of medical oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He disclosed ties with Ariad/Takeda, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech/Roche, Merck, Pfizer, and Spectrum. A version of this article originally appeared on Medscape.com.

Family medicine physician Kenneth Cheng, DO, was on-call at a local hospital when a nurse told him that a patient needing evaluation hated Asians.

“I talked to him about whether he was okay seeing me and he said yes,” Dr. Cheng said. “But I remained vigilant and conscious of what the patient was doing the whole time so he couldn’t take advantage of the situation.”

Dr. Cheng never turned his back to the patient and even backed out of the exam room. That encounter passed without incident. However, a urologist Dr. Cheng knew from residency wasn’t so fortunate. Ronald Gilbert, MD, of Newport Beach, Calif., was shot and killed by a patient in his office. The patient blamed him for complications following prostate surgery 25 years earlier.

In 2022, a gunman in Tulsa, Okla., blamed his physician for pain from a recent back surgery and shot and killed him, another physician, and two others in a medical building before taking his own life.

Nearly 9 in 10 physicians reported in a recent Medscape poll that they had experienced one or more violent or potentially violent incidents in the past year. The most common patient behaviors were verbal abuse, getting angry and leaving, and behaving erratically.

About one in three respondents said that the patients threatened to harm them, and about one in five said that the patients became violent.

Experts say that many factors contribute to this potentially lethal situation: Health care services have become more impersonal, patients experience longer wait times, some abuse prescription drugs, mental health services are lacking, and security is poor or nonexistent at some health care facilities.

Violence against hospital workers has become so common that a bill was introduced in 2022 in Congress to better protect them. The Safety From Violence for Healthcare Employees Act includes stiffer penalties for acts involving the use of a dangerous weapon or committed during a public emergency and would also provide $25 million in grants to hospitals for programs aimed at reducing violent incidents in health care settings, including de-escalation training. The American Hospital Association and American College of Emergency Physicians support the bill, which is now before the House Judiciary Subcommittee on Crime, Terrorism, and Homeland Security.
 

The worst day of their lives

“You have people who already are having the worst day of their lives and feeling on edge. If they already have a short fuse or substance abuse issues, that can translate into agitation, violence, or aggression,” said Scott Zeller, MD, vice president of acute psychiatry at Vituity, a physician-owned multispecialty group that operates in several states.

Health care workers in psychiatric and substance abuse hospitals were 10 times more likely to experience nonfatal injuries by others in 2018 than were health care workers in ambulatory settings, according to an April 2020 Bureau of Labor Statistics report. In addition, health care workers were five times more likely to suffer a workplace violence injury than were workers overall in 2018.

Psychiatrists who responded to the poll were the specialists most likely to report that they encountered violent patients and potentially violent patients. “Historically, inpatient psychiatry, which requires more acute care and monitoring, is considered the most dangerous profession outside of the police,” said Dr. Zeller.

Emergency physicians have reported an uptick in violence from patients; 85% said in a survey by ACEP in 2022 that they believed the rate of violence in emergency departments has increased over the past 5 years, whereas 45% indicated that it has greatly increased.

Some doctors have been threatened with violence or actually killed by family members. Alex Skog, MD, president-elect of ACEP’s Oregon chapter, told HealthCare Dive that “a patient’s family member with a gun holster on his hip threatened to kill me and kill my entire family after I told his father that he needed to be admitted because he had coronavirus.”

“I’ve been scared for my safety as well as the safety of my family,” Dr. Skog said. “That was just not something that we were seeing 3, 4, or 5 years ago.”

Many patients are already upset by the time they see doctors, according to the poll.

“The most common reason patients are upset is that they’re already in a lot of pain, which can be expressed as anger, hostility, or aggression. They’re very anxious and afraid of what’s happening and may be thinking about the worst-case scenario – that a bump or lump is cancer,” Dr. Zeller said.

Patients may also get upset if they disagree with their doctors’ diagnosis or treatment plan or the doctor refuses to prescribe them the drugs or tests they want.

“One doctor commented recently: ‘After over 30 years in this business, I can say patients are worse now than at any point in my career. Entitled, demanding, obnoxious. Any denial is met with outrage and indignity, whether it’s an opioid request or a demand for MRI of something because they ‘want to know.’ ”

An orthopedic surgeon in Indiana lost his life after he refused to prescribe opioids to a patient. Her angry husband shot and killed the doctor in the parking lot only 2 hours after confronting him in his office.
 

Decreased physician-patient trust

“When doctors experience something frightening, they become more apprehensive in the future. There’s no doubt that after the first violent experience, they think of things differently,” said Dr. Zeller.

More than half of the doctors who reported experiencing at least one violent or potentially violent incident in the poll said they trusted patients less.

This diminished trust can negatively impact the physician-patient relationship, said the authors of a recent Health Affairs article.

“The more patients harm their health care providers, intentionally or unintentionally, the more difficult it will be for those providers to trust them, leading to yet another unfortunate pattern: physicians pulling back on some of the behaviors thought to be most trust-building, for example, talking about their personal lives, building rapport, displaying compassion, or giving out their personal cell phone numbers,” the article stated.
 

What doctors can do

Most doctors who experienced a violent or potentially violent incident said they had tried to defuse the situation and that they succeeded at least some of the time, the poll results show.

One of the best ways to defuse a situation is to be empathetic and show the person that you’re on their side and not the enemy, said Dr. Cheng,.

“Rather than making general statements like ‘I understand that you’re upset,’ it’s better to be specific about the reason the person is upset. For example: ‘I understand that you’re upset that the pharmacy didn’t fill your prescription’ or ‘I understand how you’re feeling about Doctor So-and-so, who didn’t treat you right,’ ” Dr. Cheng stated.

Dr. Zeller urged physicians to talk to patients about why they’re upset and how they can help them. That approach worked with a patient who was having a psychotic episode.

“I told the staff, who wanted to forcibly restrain him and inject him with medication, that I would talk to him. I asked the patient, who was screaming ‘ya ya ya ya,’ whether he would take his medication if I gave it to him and he said yes. When he was calm, he explained that he was screaming to stop the voices telling him to kill his parents. He then got the help he needed,” said Dr. Zeller.

Dr. Cheng was trained in de-escalation techniques as an Orange County reserve deputy sheriff. He and Dr. Zeller recommended that physicians and staff receive training in how to spot potentially violent behavior and defuse these situations before they escalate.

Dr. Cheng suggests looking at the person’s body language for signs of increasing agitation or tension, such as clenched fists, tense posture, tight jaw, or fidgeting that may be accompanied by shouting and/or verbal abuse.

Physicians also need to consider where they are physically in relation to patients they see. “You don’t want to be too close to the patient or stand in front of them, which can be seen as confrontational. Instead, stand or sit off to the side, and never block the door if the patient’s upset,” said Dr. Cheng.

He recommended that physician practices prepare for violent incidents by developing detailed plans, including how and when to escape, how to protect patients, and how to cooperate with law enforcement.

“If a violent incident is inescapable, physicians and staff must be ready to fight back with whatever tools they have available, which may include fire extinguishers, chairs, or scalpels,” said Dr. Cheng.

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

Family medicine physician Kenneth Cheng, DO, was on-call at a local hospital when a nurse told him that a patient needing evaluation hated Asians.

“I talked to him about whether he was okay seeing me and he said yes,” Dr. Cheng said. “But I remained vigilant and conscious of what the patient was doing the whole time so he couldn’t take advantage of the situation.”

Dr. Cheng never turned his back to the patient and even backed out of the exam room. That encounter passed without incident. However, a urologist Dr. Cheng knew from residency wasn’t so fortunate. Ronald Gilbert, MD, of Newport Beach, Calif., was shot and killed by a patient in his office. The patient blamed him for complications following prostate surgery 25 years earlier.

In 2022, a gunman in Tulsa, Okla., blamed his physician for pain from a recent back surgery and shot and killed him, another physician, and two others in a medical building before taking his own life.

Nearly 9 in 10 physicians reported in a recent Medscape poll that they had experienced one or more violent or potentially violent incidents in the past year. The most common patient behaviors were verbal abuse, getting angry and leaving, and behaving erratically.

About one in three respondents said that the patients threatened to harm them, and about one in five said that the patients became violent.

Experts say that many factors contribute to this potentially lethal situation: Health care services have become more impersonal, patients experience longer wait times, some abuse prescription drugs, mental health services are lacking, and security is poor or nonexistent at some health care facilities.

Violence against hospital workers has become so common that a bill was introduced in 2022 in Congress to better protect them. The Safety From Violence for Healthcare Employees Act includes stiffer penalties for acts involving the use of a dangerous weapon or committed during a public emergency and would also provide $25 million in grants to hospitals for programs aimed at reducing violent incidents in health care settings, including de-escalation training. The American Hospital Association and American College of Emergency Physicians support the bill, which is now before the House Judiciary Subcommittee on Crime, Terrorism, and Homeland Security.
 

The worst day of their lives

“You have people who already are having the worst day of their lives and feeling on edge. If they already have a short fuse or substance abuse issues, that can translate into agitation, violence, or aggression,” said Scott Zeller, MD, vice president of acute psychiatry at Vituity, a physician-owned multispecialty group that operates in several states.

Health care workers in psychiatric and substance abuse hospitals were 10 times more likely to experience nonfatal injuries by others in 2018 than were health care workers in ambulatory settings, according to an April 2020 Bureau of Labor Statistics report. In addition, health care workers were five times more likely to suffer a workplace violence injury than were workers overall in 2018.

Psychiatrists who responded to the poll were the specialists most likely to report that they encountered violent patients and potentially violent patients. “Historically, inpatient psychiatry, which requires more acute care and monitoring, is considered the most dangerous profession outside of the police,” said Dr. Zeller.

Emergency physicians have reported an uptick in violence from patients; 85% said in a survey by ACEP in 2022 that they believed the rate of violence in emergency departments has increased over the past 5 years, whereas 45% indicated that it has greatly increased.

Some doctors have been threatened with violence or actually killed by family members. Alex Skog, MD, president-elect of ACEP’s Oregon chapter, told HealthCare Dive that “a patient’s family member with a gun holster on his hip threatened to kill me and kill my entire family after I told his father that he needed to be admitted because he had coronavirus.”

“I’ve been scared for my safety as well as the safety of my family,” Dr. Skog said. “That was just not something that we were seeing 3, 4, or 5 years ago.”

Many patients are already upset by the time they see doctors, according to the poll.

“The most common reason patients are upset is that they’re already in a lot of pain, which can be expressed as anger, hostility, or aggression. They’re very anxious and afraid of what’s happening and may be thinking about the worst-case scenario – that a bump or lump is cancer,” Dr. Zeller said.

Patients may also get upset if they disagree with their doctors’ diagnosis or treatment plan or the doctor refuses to prescribe them the drugs or tests they want.

“One doctor commented recently: ‘After over 30 years in this business, I can say patients are worse now than at any point in my career. Entitled, demanding, obnoxious. Any denial is met with outrage and indignity, whether it’s an opioid request or a demand for MRI of something because they ‘want to know.’ ”

An orthopedic surgeon in Indiana lost his life after he refused to prescribe opioids to a patient. Her angry husband shot and killed the doctor in the parking lot only 2 hours after confronting him in his office.
 

Decreased physician-patient trust

“When doctors experience something frightening, they become more apprehensive in the future. There’s no doubt that after the first violent experience, they think of things differently,” said Dr. Zeller.

More than half of the doctors who reported experiencing at least one violent or potentially violent incident in the poll said they trusted patients less.

This diminished trust can negatively impact the physician-patient relationship, said the authors of a recent Health Affairs article.

“The more patients harm their health care providers, intentionally or unintentionally, the more difficult it will be for those providers to trust them, leading to yet another unfortunate pattern: physicians pulling back on some of the behaviors thought to be most trust-building, for example, talking about their personal lives, building rapport, displaying compassion, or giving out their personal cell phone numbers,” the article stated.
 

What doctors can do

Most doctors who experienced a violent or potentially violent incident said they had tried to defuse the situation and that they succeeded at least some of the time, the poll results show.

One of the best ways to defuse a situation is to be empathetic and show the person that you’re on their side and not the enemy, said Dr. Cheng,.

“Rather than making general statements like ‘I understand that you’re upset,’ it’s better to be specific about the reason the person is upset. For example: ‘I understand that you’re upset that the pharmacy didn’t fill your prescription’ or ‘I understand how you’re feeling about Doctor So-and-so, who didn’t treat you right,’ ” Dr. Cheng stated.

Dr. Zeller urged physicians to talk to patients about why they’re upset and how they can help them. That approach worked with a patient who was having a psychotic episode.

“I told the staff, who wanted to forcibly restrain him and inject him with medication, that I would talk to him. I asked the patient, who was screaming ‘ya ya ya ya,’ whether he would take his medication if I gave it to him and he said yes. When he was calm, he explained that he was screaming to stop the voices telling him to kill his parents. He then got the help he needed,” said Dr. Zeller.

Dr. Cheng was trained in de-escalation techniques as an Orange County reserve deputy sheriff. He and Dr. Zeller recommended that physicians and staff receive training in how to spot potentially violent behavior and defuse these situations before they escalate.

Dr. Cheng suggests looking at the person’s body language for signs of increasing agitation or tension, such as clenched fists, tense posture, tight jaw, or fidgeting that may be accompanied by shouting and/or verbal abuse.

Physicians also need to consider where they are physically in relation to patients they see. “You don’t want to be too close to the patient or stand in front of them, which can be seen as confrontational. Instead, stand or sit off to the side, and never block the door if the patient’s upset,” said Dr. Cheng.

He recommended that physician practices prepare for violent incidents by developing detailed plans, including how and when to escape, how to protect patients, and how to cooperate with law enforcement.

“If a violent incident is inescapable, physicians and staff must be ready to fight back with whatever tools they have available, which may include fire extinguishers, chairs, or scalpels,” said Dr. Cheng.

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

Family medicine physician Kenneth Cheng, DO, was on-call at a local hospital when a nurse told him that a patient needing evaluation hated Asians.

“I talked to him about whether he was okay seeing me and he said yes,” Dr. Cheng said. “But I remained vigilant and conscious of what the patient was doing the whole time so he couldn’t take advantage of the situation.”

Dr. Cheng never turned his back to the patient and even backed out of the exam room. That encounter passed without incident. However, a urologist Dr. Cheng knew from residency wasn’t so fortunate. Ronald Gilbert, MD, of Newport Beach, Calif., was shot and killed by a patient in his office. The patient blamed him for complications following prostate surgery 25 years earlier.

In 2022, a gunman in Tulsa, Okla., blamed his physician for pain from a recent back surgery and shot and killed him, another physician, and two others in a medical building before taking his own life.

Nearly 9 in 10 physicians reported in a recent Medscape poll that they had experienced one or more violent or potentially violent incidents in the past year. The most common patient behaviors were verbal abuse, getting angry and leaving, and behaving erratically.

About one in three respondents said that the patients threatened to harm them, and about one in five said that the patients became violent.

Experts say that many factors contribute to this potentially lethal situation: Health care services have become more impersonal, patients experience longer wait times, some abuse prescription drugs, mental health services are lacking, and security is poor or nonexistent at some health care facilities.

Violence against hospital workers has become so common that a bill was introduced in 2022 in Congress to better protect them. The Safety From Violence for Healthcare Employees Act includes stiffer penalties for acts involving the use of a dangerous weapon or committed during a public emergency and would also provide $25 million in grants to hospitals for programs aimed at reducing violent incidents in health care settings, including de-escalation training. The American Hospital Association and American College of Emergency Physicians support the bill, which is now before the House Judiciary Subcommittee on Crime, Terrorism, and Homeland Security.
 

The worst day of their lives

“You have people who already are having the worst day of their lives and feeling on edge. If they already have a short fuse or substance abuse issues, that can translate into agitation, violence, or aggression,” said Scott Zeller, MD, vice president of acute psychiatry at Vituity, a physician-owned multispecialty group that operates in several states.

Health care workers in psychiatric and substance abuse hospitals were 10 times more likely to experience nonfatal injuries by others in 2018 than were health care workers in ambulatory settings, according to an April 2020 Bureau of Labor Statistics report. In addition, health care workers were five times more likely to suffer a workplace violence injury than were workers overall in 2018.

Psychiatrists who responded to the poll were the specialists most likely to report that they encountered violent patients and potentially violent patients. “Historically, inpatient psychiatry, which requires more acute care and monitoring, is considered the most dangerous profession outside of the police,” said Dr. Zeller.

Emergency physicians have reported an uptick in violence from patients; 85% said in a survey by ACEP in 2022 that they believed the rate of violence in emergency departments has increased over the past 5 years, whereas 45% indicated that it has greatly increased.

Some doctors have been threatened with violence or actually killed by family members. Alex Skog, MD, president-elect of ACEP’s Oregon chapter, told HealthCare Dive that “a patient’s family member with a gun holster on his hip threatened to kill me and kill my entire family after I told his father that he needed to be admitted because he had coronavirus.”

“I’ve been scared for my safety as well as the safety of my family,” Dr. Skog said. “That was just not something that we were seeing 3, 4, or 5 years ago.”

Many patients are already upset by the time they see doctors, according to the poll.

“The most common reason patients are upset is that they’re already in a lot of pain, which can be expressed as anger, hostility, or aggression. They’re very anxious and afraid of what’s happening and may be thinking about the worst-case scenario – that a bump or lump is cancer,” Dr. Zeller said.

Patients may also get upset if they disagree with their doctors’ diagnosis or treatment plan or the doctor refuses to prescribe them the drugs or tests they want.

“One doctor commented recently: ‘After over 30 years in this business, I can say patients are worse now than at any point in my career. Entitled, demanding, obnoxious. Any denial is met with outrage and indignity, whether it’s an opioid request or a demand for MRI of something because they ‘want to know.’ ”

An orthopedic surgeon in Indiana lost his life after he refused to prescribe opioids to a patient. Her angry husband shot and killed the doctor in the parking lot only 2 hours after confronting him in his office.
 

Decreased physician-patient trust

“When doctors experience something frightening, they become more apprehensive in the future. There’s no doubt that after the first violent experience, they think of things differently,” said Dr. Zeller.

More than half of the doctors who reported experiencing at least one violent or potentially violent incident in the poll said they trusted patients less.

This diminished trust can negatively impact the physician-patient relationship, said the authors of a recent Health Affairs article.

“The more patients harm their health care providers, intentionally or unintentionally, the more difficult it will be for those providers to trust them, leading to yet another unfortunate pattern: physicians pulling back on some of the behaviors thought to be most trust-building, for example, talking about their personal lives, building rapport, displaying compassion, or giving out their personal cell phone numbers,” the article stated.
 

What doctors can do

Most doctors who experienced a violent or potentially violent incident said they had tried to defuse the situation and that they succeeded at least some of the time, the poll results show.

One of the best ways to defuse a situation is to be empathetic and show the person that you’re on their side and not the enemy, said Dr. Cheng,.

“Rather than making general statements like ‘I understand that you’re upset,’ it’s better to be specific about the reason the person is upset. For example: ‘I understand that you’re upset that the pharmacy didn’t fill your prescription’ or ‘I understand how you’re feeling about Doctor So-and-so, who didn’t treat you right,’ ” Dr. Cheng stated.

Dr. Zeller urged physicians to talk to patients about why they’re upset and how they can help them. That approach worked with a patient who was having a psychotic episode.

“I told the staff, who wanted to forcibly restrain him and inject him with medication, that I would talk to him. I asked the patient, who was screaming ‘ya ya ya ya,’ whether he would take his medication if I gave it to him and he said yes. When he was calm, he explained that he was screaming to stop the voices telling him to kill his parents. He then got the help he needed,” said Dr. Zeller.

Dr. Cheng was trained in de-escalation techniques as an Orange County reserve deputy sheriff. He and Dr. Zeller recommended that physicians and staff receive training in how to spot potentially violent behavior and defuse these situations before they escalate.

Dr. Cheng suggests looking at the person’s body language for signs of increasing agitation or tension, such as clenched fists, tense posture, tight jaw, or fidgeting that may be accompanied by shouting and/or verbal abuse.

Physicians also need to consider where they are physically in relation to patients they see. “You don’t want to be too close to the patient or stand in front of them, which can be seen as confrontational. Instead, stand or sit off to the side, and never block the door if the patient’s upset,” said Dr. Cheng.

He recommended that physician practices prepare for violent incidents by developing detailed plans, including how and when to escape, how to protect patients, and how to cooperate with law enforcement.

“If a violent incident is inescapable, physicians and staff must be ready to fight back with whatever tools they have available, which may include fire extinguishers, chairs, or scalpels,” said Dr. Cheng.

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

A new meta-analysis has added evidence questioning the utility and efficacy of prophylactic low-dose aspirin for preventing cardiovascular events in people who don’t have atherosclerotic cardiovascular disease (ASCVD), whether or not they’re also taking statins, and finds that at every level of ASCVD risk the aspirin carries a risk of major bleeding that exceeds its potentially protective benefits.

In a study published online in JACC: Advances, the researchers, led by Safi U. Khan, MD, MS, analyzed data from 16 trials with 171,215 individuals, with a median age of 64 years. Of the population analyzed, 35% were taking statins.

“This study focused on patients without ASCVD who are taking aspirin with or without statin therapy to prevent ASCVD events,” Dr. Khan, a cardiovascular disease fellow at Houston Methodist DeBakey Heart and Vascular Institute, told this news organization. “We noted that the absolute risk of major bleeding in this patient population exceeds the absolute reduction in MI by aspirin across different ASCVD risk categories. Furthermore, concomitant statin therapy use further diminishes aspirin’s cardiovascular effects without influencing bleeding risk.”

Across the 16 studies, people taking aspirin had a relative risk reduction of 15% for MI vs. controls (RR .85; 95% confidence interval [CI], .77 to .95; P < .001). However, they had a 48% greater risk of major bleeding (RR, 1.48; 95% CI, 1.31-1.66; P < .001).

The meta-analysis also found that aspirin, either as monotherapy or with a statin, carried a slight to significant benefit depending on the estimated risk of developing ASCVD. The risk of major bleeding exceeded the benefit across all three risk-stratified groups. The greatest benefit, and greatest risk, was in the groups with high to very-high ASCVD risk groups, defined as a 20%-30% and 30% or greater ASCVD risk, respectively: 20-37 fewer MIs per 10,000 with monotherapy and 27-49 fewer with statin, but 78-98 more major bleeding events with monotherapy and 74-95 more with statin.

And aspirin, either as monotherapy or with statin, didn’t reduce the risk of other key endpoints: stroke, all-cause mortality, or cardiovascular mortality. While aspirin was associated with a lower risk of nonfatal MI (RR, .82; 95% CI, .72 to .94; P ≤. 001), it  wasn’t associated with reducing the risk of nonfatal stroke. Aspirin patients had a significantly 32% greater risk of intracranial hemorrhage (RR, 1.32; 95% CI, 1.12-1.55; P ≤ .001) and 51% increased risk of gastrointestinal bleeding (RR, 1.51; 95% CI, 1.33-1.72; P ≤ .001).

“We used randomized data from all key primary prevention of aspirin trials and estimated the absolute effects of aspirin therapy with or without concomitant statin across different baseline risks of the patients,” Dr. Khan said. “This approach allowed us to identify aspirin therapy’s risk-benefit equilibrium, which is tilted towards more harm than benefit.”

He acknowledged study limitations included using study-level rather than patient-level meta-analysis, and the inability to calculate effects in younger populations at high absolute risk.  

The investigators acknowledged the controversy surrounding aspirin use to prevent ASCVD, noting the three major guidelines: the 2019 American College of Cardiology/American Heart Association and the 2021 European Society of Cardiology guidelines for aspirin only among asymptomatic individuals with high risk of ASCVD events, low bleeding risk, and age 70 years and younger; and the United States Preventive Services Task Force guidelines, updated in 2022, recommending individualized low-dose aspirin only among adults ages 40-59 years with 10-year ASCVD risk of 10% or greater and a low bleeding risk.

The findings are not a clarion call to halt aspirin therapy, Dr. Khan said. “This research focuses only on patients who do not have ASCVD,” he said. “Patients who do have ASCVD should continue with aspirin and statin therapy. However, we noted that aspirin has a limited role for patients who do not have ASCVD beyond lifestyle modifications, smoking cessation, exercise, and preventive statin therapy. Therefore, they should only consider using aspirin if their physicians suggest that the risk of having a cardiovascular event exceeds their bleeding risk. Otherwise, they should discuss with their physicians about omitting aspirin.”

The study confirms the move away from low-dose aspirin to prevent ASCVD, said Tahmid Rahman, MD, cardiologist and associate director of the Center for Advanced Lipid Management at Stony Brook (N.Y.) Heart Institute. “The study really continues to add to essentially what we already know,” he said. “There was a big push that aspirin, initially before the major statin trials, was the way to go to prevent heart disease, but with later studies, and especially now with newer antiplatelet therapies and longer duration of medication for people with both secondary prevention and primary prevention, we are getting away from routine aspirin, especially in primary prevention.”

A new meta-analysis has added evidence questioning the utility and efficacy of prophylactic low-dose aspirin for preventing cardiovascular events in people who don’t have atherosclerotic cardiovascular disease (ASCVD), whether or not they’re also taking statins, and finds that at every level of ASCVD risk the aspirin carries a risk of major bleeding that exceeds its potentially protective benefits.

In a study published online in JACC: Advances, the researchers, led by Safi U. Khan, MD, MS, analyzed data from 16 trials with 171,215 individuals, with a median age of 64 years. Of the population analyzed, 35% were taking statins.

“This study focused on patients without ASCVD who are taking aspirin with or without statin therapy to prevent ASCVD events,” Dr. Khan, a cardiovascular disease fellow at Houston Methodist DeBakey Heart and Vascular Institute, told this news organization. “We noted that the absolute risk of major bleeding in this patient population exceeds the absolute reduction in MI by aspirin across different ASCVD risk categories. Furthermore, concomitant statin therapy use further diminishes aspirin’s cardiovascular effects without influencing bleeding risk.”

Across the 16 studies, people taking aspirin had a relative risk reduction of 15% for MI vs. controls (RR .85; 95% confidence interval [CI], .77 to .95; P < .001). However, they had a 48% greater risk of major bleeding (RR, 1.48; 95% CI, 1.31-1.66; P < .001).

The meta-analysis also found that aspirin, either as monotherapy or with a statin, carried a slight to significant benefit depending on the estimated risk of developing ASCVD. The risk of major bleeding exceeded the benefit across all three risk-stratified groups. The greatest benefit, and greatest risk, was in the groups with high to very-high ASCVD risk groups, defined as a 20%-30% and 30% or greater ASCVD risk, respectively: 20-37 fewer MIs per 10,000 with monotherapy and 27-49 fewer with statin, but 78-98 more major bleeding events with monotherapy and 74-95 more with statin.

And aspirin, either as monotherapy or with statin, didn’t reduce the risk of other key endpoints: stroke, all-cause mortality, or cardiovascular mortality. While aspirin was associated with a lower risk of nonfatal MI (RR, .82; 95% CI, .72 to .94; P ≤. 001), it  wasn’t associated with reducing the risk of nonfatal stroke. Aspirin patients had a significantly 32% greater risk of intracranial hemorrhage (RR, 1.32; 95% CI, 1.12-1.55; P ≤ .001) and 51% increased risk of gastrointestinal bleeding (RR, 1.51; 95% CI, 1.33-1.72; P ≤ .001).

“We used randomized data from all key primary prevention of aspirin trials and estimated the absolute effects of aspirin therapy with or without concomitant statin across different baseline risks of the patients,” Dr. Khan said. “This approach allowed us to identify aspirin therapy’s risk-benefit equilibrium, which is tilted towards more harm than benefit.”

He acknowledged study limitations included using study-level rather than patient-level meta-analysis, and the inability to calculate effects in younger populations at high absolute risk.  

The investigators acknowledged the controversy surrounding aspirin use to prevent ASCVD, noting the three major guidelines: the 2019 American College of Cardiology/American Heart Association and the 2021 European Society of Cardiology guidelines for aspirin only among asymptomatic individuals with high risk of ASCVD events, low bleeding risk, and age 70 years and younger; and the United States Preventive Services Task Force guidelines, updated in 2022, recommending individualized low-dose aspirin only among adults ages 40-59 years with 10-year ASCVD risk of 10% or greater and a low bleeding risk.

The findings are not a clarion call to halt aspirin therapy, Dr. Khan said. “This research focuses only on patients who do not have ASCVD,” he said. “Patients who do have ASCVD should continue with aspirin and statin therapy. However, we noted that aspirin has a limited role for patients who do not have ASCVD beyond lifestyle modifications, smoking cessation, exercise, and preventive statin therapy. Therefore, they should only consider using aspirin if their physicians suggest that the risk of having a cardiovascular event exceeds their bleeding risk. Otherwise, they should discuss with their physicians about omitting aspirin.”

The study confirms the move away from low-dose aspirin to prevent ASCVD, said Tahmid Rahman, MD, cardiologist and associate director of the Center for Advanced Lipid Management at Stony Brook (N.Y.) Heart Institute. “The study really continues to add to essentially what we already know,” he said. “There was a big push that aspirin, initially before the major statin trials, was the way to go to prevent heart disease, but with later studies, and especially now with newer antiplatelet therapies and longer duration of medication for people with both secondary prevention and primary prevention, we are getting away from routine aspirin, especially in primary prevention.”

A new meta-analysis has added evidence questioning the utility and efficacy of prophylactic low-dose aspirin for preventing cardiovascular events in people who don’t have atherosclerotic cardiovascular disease (ASCVD), whether or not they’re also taking statins, and finds that at every level of ASCVD risk the aspirin carries a risk of major bleeding that exceeds its potentially protective benefits.

In a study published online in JACC: Advances, the researchers, led by Safi U. Khan, MD, MS, analyzed data from 16 trials with 171,215 individuals, with a median age of 64 years. Of the population analyzed, 35% were taking statins.

“This study focused on patients without ASCVD who are taking aspirin with or without statin therapy to prevent ASCVD events,” Dr. Khan, a cardiovascular disease fellow at Houston Methodist DeBakey Heart and Vascular Institute, told this news organization. “We noted that the absolute risk of major bleeding in this patient population exceeds the absolute reduction in MI by aspirin across different ASCVD risk categories. Furthermore, concomitant statin therapy use further diminishes aspirin’s cardiovascular effects without influencing bleeding risk.”

Across the 16 studies, people taking aspirin had a relative risk reduction of 15% for MI vs. controls (RR .85; 95% confidence interval [CI], .77 to .95; P < .001). However, they had a 48% greater risk of major bleeding (RR, 1.48; 95% CI, 1.31-1.66; P < .001).

The meta-analysis also found that aspirin, either as monotherapy or with a statin, carried a slight to significant benefit depending on the estimated risk of developing ASCVD. The risk of major bleeding exceeded the benefit across all three risk-stratified groups. The greatest benefit, and greatest risk, was in the groups with high to very-high ASCVD risk groups, defined as a 20%-30% and 30% or greater ASCVD risk, respectively: 20-37 fewer MIs per 10,000 with monotherapy and 27-49 fewer with statin, but 78-98 more major bleeding events with monotherapy and 74-95 more with statin.

And aspirin, either as monotherapy or with statin, didn’t reduce the risk of other key endpoints: stroke, all-cause mortality, or cardiovascular mortality. While aspirin was associated with a lower risk of nonfatal MI (RR, .82; 95% CI, .72 to .94; P ≤. 001), it  wasn’t associated with reducing the risk of nonfatal stroke. Aspirin patients had a significantly 32% greater risk of intracranial hemorrhage (RR, 1.32; 95% CI, 1.12-1.55; P ≤ .001) and 51% increased risk of gastrointestinal bleeding (RR, 1.51; 95% CI, 1.33-1.72; P ≤ .001).

“We used randomized data from all key primary prevention of aspirin trials and estimated the absolute effects of aspirin therapy with or without concomitant statin across different baseline risks of the patients,” Dr. Khan said. “This approach allowed us to identify aspirin therapy’s risk-benefit equilibrium, which is tilted towards more harm than benefit.”

He acknowledged study limitations included using study-level rather than patient-level meta-analysis, and the inability to calculate effects in younger populations at high absolute risk.  

The investigators acknowledged the controversy surrounding aspirin use to prevent ASCVD, noting the three major guidelines: the 2019 American College of Cardiology/American Heart Association and the 2021 European Society of Cardiology guidelines for aspirin only among asymptomatic individuals with high risk of ASCVD events, low bleeding risk, and age 70 years and younger; and the United States Preventive Services Task Force guidelines, updated in 2022, recommending individualized low-dose aspirin only among adults ages 40-59 years with 10-year ASCVD risk of 10% or greater and a low bleeding risk.

The findings are not a clarion call to halt aspirin therapy, Dr. Khan said. “This research focuses only on patients who do not have ASCVD,” he said. “Patients who do have ASCVD should continue with aspirin and statin therapy. However, we noted that aspirin has a limited role for patients who do not have ASCVD beyond lifestyle modifications, smoking cessation, exercise, and preventive statin therapy. Therefore, they should only consider using aspirin if their physicians suggest that the risk of having a cardiovascular event exceeds their bleeding risk. Otherwise, they should discuss with their physicians about omitting aspirin.”

The study confirms the move away from low-dose aspirin to prevent ASCVD, said Tahmid Rahman, MD, cardiologist and associate director of the Center for Advanced Lipid Management at Stony Brook (N.Y.) Heart Institute. “The study really continues to add to essentially what we already know,” he said. “There was a big push that aspirin, initially before the major statin trials, was the way to go to prevent heart disease, but with later studies, and especially now with newer antiplatelet therapies and longer duration of medication for people with both secondary prevention and primary prevention, we are getting away from routine aspirin, especially in primary prevention.”

Hospitalized COVID-19 patients with high troponin levels are twice as likely to have cardiac abnormalities than those with normal troponin, with or without COVID-19, a multicenter U.K. study suggests.

The causes were diverse, myocarditis prevalence was lower than previously reported, and myocardial scar emerged as an independent risk factor for adverse cardiovascular outcomes at 12 months.

“We know that multiorgan involvement in hospitalized patients with COVID-19 is common ... and may result in acute myocardial injury, detected by an increase in cardiac troponin concentrations,” John P. Greenwood, PhD, of the University of Leeds (England), told this news organization. “Elevated cardiac troponin is associated with a worse prognosis.”

“Multiple mechanisms of myocardial injury have been proposed and ... mitigation or prevention strategies likely depend on the underpinning mechanisms,” he said. “The sequelae of scar may predispose to late events.”

The study, published online  in Circulation, also identified a new pattern of microinfarction on cardiac magnetic resonance (CMR) imaging, highlighting the pro-thrombotic nature of SARS-CoV-2, Dr. Greenwood said.
 

Injury patterns different

Three hundred and forty-two patients with COVID-19 and elevated troponin levels (COVID+/troponin+) across 25 centers were enrolled between June 2020 and March 2021 in COVID-HEART, deemed an “urgent public health study” in the United Kingdom. The aim was to characterize myocardial injury and its associations and sequelae in convalescent patients after hospitalization with COVID-19.

Enrollment took place during the Wuhan and Alpha waves of COVID-19: before vaccination and when dexamethasone and anticoagulant protocols were emerging. All participants underwent CMR at a median of 21 days after discharge.

Two prospective control groups also were recruited: 64 patients with COVID-19 and normal troponin levels (COVID+/troponin−) and 113 without COVID-19 or elevated troponin matched by age and cardiovascular comorbidities (COVID−/comorbidity+).

Overall, participants’ median age was 61 years and 69% were men. Common comorbidities included hypertension (47%), obesity (43%), and diabetes (25%).

The frequency of any heart abnormality – for example, left or right ventricular impairment, scar, or pericardial disease – was twice as great (61%) in COVID+/troponin+ cases, compared with controls (36% for COVID+/troponin− patients versus 31% for COVID−/comorbidity+ patients).

Specifically, more cases than controls had ventricular impairment (17.2% vs. 3.1% and 7.1%) or scar (42% vs. 7% and 23%).

The myocardial injury pattern differed between cases and controls, with cases more likely to have infarction (13% vs. 2% and 7%) or microinfarction (9% vs. 0% and 1%).

However, there was no between-group difference in nonischemic scar (13% vs. 5% and 14%).

The prevalence of probable recent myocarditis was 6.7% in cases, compared with 1.7% in controls without COVID-19 – “much lower” than in previous studies, Dr. Greenwood noted.

During follow-up, four COVID+/troponin+ patients (1.2%) died, and 34 (10%) experienced a subsequent major adverse cardiovascular event (MACE; 10.2%), which was similar to controls (6.1%).

Myocardial scar, but not previous COVID-19 infection or troponin level, was an independent predictor of MACE (odds ratio, 2.25).

“These findings suggest that macroangiopathic and microangiopathic thrombosis may be the key pathologic process for myocardial injury in COVID-19 survivors,” the authors conclude.

Dr. Greenwood added, “We are currently analyzing the 6-month follow-up CMR scans, the quality-of-life questionnaires, and the 6-minute walk tests. These will give us great understanding of how the heart repairs after acute myocardial injury associated with COVID-19. It will also allow us to assess the impact on patient quality of life and functional capacity.”
 

‘Tour de force’

James A. de Lemos, MD, co-chair of the American Heart Association’s COVID-19 CVD Registry Steering Committee and a professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said, “This is a tour de force collaboration – obtaining this many MRIs across multiple centers in the pandemic is quite remarkable. The study highlights the multiple different processes that lead to cardiac injury in COVID patients, complements autopsy studies and prior smaller MRI studies, [and] also provides the best data on the rate of myocarditis to date among the subset of COVID patients with cardiac injury.”

Overall, he said, the findings “do support closer follow-up for patients who had COVID and elevated troponins. We need to see follow-up MRI results in this cohort, as well as longer term outcomes. We also need studies on newer, more benign variants that are likely to have lower rates of cardiac injury and even fewer MRI abnormalities.”

Matthias Stuber, PhD, and Aaron L. Baggish, MD, both of Lausanne University Hospital and University of Lausanne, Switzerland, noted in a related editorial, “We are also reminded that the clinical severity of COVID-19 is most often dictated by the presence of pre-existing comorbidity, with antecedent ischemic scar now added to the long list of bad actors. Although not the primary focus of the COVID-HEART study, the question of whether cardiac troponin levels should be checked routinely and universally during the index admission for COVID-19 remains unresolved,” they noted.

“In general, we are most effective as clinicians when we use tests to confirm or rule out the specific disease processes suspected by careful basic clinical assessment rather than in a shotgun manner among undifferentiated all-comers,” they conclude.

No commercial funding or relevant financial relationships were reported.

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

Hospitalized COVID-19 patients with high troponin levels are twice as likely to have cardiac abnormalities than those with normal troponin, with or without COVID-19, a multicenter U.K. study suggests.

The causes were diverse, myocarditis prevalence was lower than previously reported, and myocardial scar emerged as an independent risk factor for adverse cardiovascular outcomes at 12 months.

“We know that multiorgan involvement in hospitalized patients with COVID-19 is common ... and may result in acute myocardial injury, detected by an increase in cardiac troponin concentrations,” John P. Greenwood, PhD, of the University of Leeds (England), told this news organization. “Elevated cardiac troponin is associated with a worse prognosis.”

“Multiple mechanisms of myocardial injury have been proposed and ... mitigation or prevention strategies likely depend on the underpinning mechanisms,” he said. “The sequelae of scar may predispose to late events.”

The study, published online  in Circulation, also identified a new pattern of microinfarction on cardiac magnetic resonance (CMR) imaging, highlighting the pro-thrombotic nature of SARS-CoV-2, Dr. Greenwood said.
 

Injury patterns different

Three hundred and forty-two patients with COVID-19 and elevated troponin levels (COVID+/troponin+) across 25 centers were enrolled between June 2020 and March 2021 in COVID-HEART, deemed an “urgent public health study” in the United Kingdom. The aim was to characterize myocardial injury and its associations and sequelae in convalescent patients after hospitalization with COVID-19.

Enrollment took place during the Wuhan and Alpha waves of COVID-19: before vaccination and when dexamethasone and anticoagulant protocols were emerging. All participants underwent CMR at a median of 21 days after discharge.

Two prospective control groups also were recruited: 64 patients with COVID-19 and normal troponin levels (COVID+/troponin−) and 113 without COVID-19 or elevated troponin matched by age and cardiovascular comorbidities (COVID−/comorbidity+).

Overall, participants’ median age was 61 years and 69% were men. Common comorbidities included hypertension (47%), obesity (43%), and diabetes (25%).

The frequency of any heart abnormality – for example, left or right ventricular impairment, scar, or pericardial disease – was twice as great (61%) in COVID+/troponin+ cases, compared with controls (36% for COVID+/troponin− patients versus 31% for COVID−/comorbidity+ patients).

Specifically, more cases than controls had ventricular impairment (17.2% vs. 3.1% and 7.1%) or scar (42% vs. 7% and 23%).

The myocardial injury pattern differed between cases and controls, with cases more likely to have infarction (13% vs. 2% and 7%) or microinfarction (9% vs. 0% and 1%).

However, there was no between-group difference in nonischemic scar (13% vs. 5% and 14%).

The prevalence of probable recent myocarditis was 6.7% in cases, compared with 1.7% in controls without COVID-19 – “much lower” than in previous studies, Dr. Greenwood noted.

During follow-up, four COVID+/troponin+ patients (1.2%) died, and 34 (10%) experienced a subsequent major adverse cardiovascular event (MACE; 10.2%), which was similar to controls (6.1%).

Myocardial scar, but not previous COVID-19 infection or troponin level, was an independent predictor of MACE (odds ratio, 2.25).

“These findings suggest that macroangiopathic and microangiopathic thrombosis may be the key pathologic process for myocardial injury in COVID-19 survivors,” the authors conclude.

Dr. Greenwood added, “We are currently analyzing the 6-month follow-up CMR scans, the quality-of-life questionnaires, and the 6-minute walk tests. These will give us great understanding of how the heart repairs after acute myocardial injury associated with COVID-19. It will also allow us to assess the impact on patient quality of life and functional capacity.”
 

‘Tour de force’

James A. de Lemos, MD, co-chair of the American Heart Association’s COVID-19 CVD Registry Steering Committee and a professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said, “This is a tour de force collaboration – obtaining this many MRIs across multiple centers in the pandemic is quite remarkable. The study highlights the multiple different processes that lead to cardiac injury in COVID patients, complements autopsy studies and prior smaller MRI studies, [and] also provides the best data on the rate of myocarditis to date among the subset of COVID patients with cardiac injury.”

Overall, he said, the findings “do support closer follow-up for patients who had COVID and elevated troponins. We need to see follow-up MRI results in this cohort, as well as longer term outcomes. We also need studies on newer, more benign variants that are likely to have lower rates of cardiac injury and even fewer MRI abnormalities.”

Matthias Stuber, PhD, and Aaron L. Baggish, MD, both of Lausanne University Hospital and University of Lausanne, Switzerland, noted in a related editorial, “We are also reminded that the clinical severity of COVID-19 is most often dictated by the presence of pre-existing comorbidity, with antecedent ischemic scar now added to the long list of bad actors. Although not the primary focus of the COVID-HEART study, the question of whether cardiac troponin levels should be checked routinely and universally during the index admission for COVID-19 remains unresolved,” they noted.

“In general, we are most effective as clinicians when we use tests to confirm or rule out the specific disease processes suspected by careful basic clinical assessment rather than in a shotgun manner among undifferentiated all-comers,” they conclude.

No commercial funding or relevant financial relationships were reported.

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

Hospitalized COVID-19 patients with high troponin levels are twice as likely to have cardiac abnormalities than those with normal troponin, with or without COVID-19, a multicenter U.K. study suggests.

The causes were diverse, myocarditis prevalence was lower than previously reported, and myocardial scar emerged as an independent risk factor for adverse cardiovascular outcomes at 12 months.

“We know that multiorgan involvement in hospitalized patients with COVID-19 is common ... and may result in acute myocardial injury, detected by an increase in cardiac troponin concentrations,” John P. Greenwood, PhD, of the University of Leeds (England), told this news organization. “Elevated cardiac troponin is associated with a worse prognosis.”

“Multiple mechanisms of myocardial injury have been proposed and ... mitigation or prevention strategies likely depend on the underpinning mechanisms,” he said. “The sequelae of scar may predispose to late events.”

The study, published online  in Circulation, also identified a new pattern of microinfarction on cardiac magnetic resonance (CMR) imaging, highlighting the pro-thrombotic nature of SARS-CoV-2, Dr. Greenwood said.
 

Injury patterns different

Three hundred and forty-two patients with COVID-19 and elevated troponin levels (COVID+/troponin+) across 25 centers were enrolled between June 2020 and March 2021 in COVID-HEART, deemed an “urgent public health study” in the United Kingdom. The aim was to characterize myocardial injury and its associations and sequelae in convalescent patients after hospitalization with COVID-19.

Enrollment took place during the Wuhan and Alpha waves of COVID-19: before vaccination and when dexamethasone and anticoagulant protocols were emerging. All participants underwent CMR at a median of 21 days after discharge.

Two prospective control groups also were recruited: 64 patients with COVID-19 and normal troponin levels (COVID+/troponin−) and 113 without COVID-19 or elevated troponin matched by age and cardiovascular comorbidities (COVID−/comorbidity+).

Overall, participants’ median age was 61 years and 69% were men. Common comorbidities included hypertension (47%), obesity (43%), and diabetes (25%).

The frequency of any heart abnormality – for example, left or right ventricular impairment, scar, or pericardial disease – was twice as great (61%) in COVID+/troponin+ cases, compared with controls (36% for COVID+/troponin− patients versus 31% for COVID−/comorbidity+ patients).

Specifically, more cases than controls had ventricular impairment (17.2% vs. 3.1% and 7.1%) or scar (42% vs. 7% and 23%).

The myocardial injury pattern differed between cases and controls, with cases more likely to have infarction (13% vs. 2% and 7%) or microinfarction (9% vs. 0% and 1%).

However, there was no between-group difference in nonischemic scar (13% vs. 5% and 14%).

The prevalence of probable recent myocarditis was 6.7% in cases, compared with 1.7% in controls without COVID-19 – “much lower” than in previous studies, Dr. Greenwood noted.

During follow-up, four COVID+/troponin+ patients (1.2%) died, and 34 (10%) experienced a subsequent major adverse cardiovascular event (MACE; 10.2%), which was similar to controls (6.1%).

Myocardial scar, but not previous COVID-19 infection or troponin level, was an independent predictor of MACE (odds ratio, 2.25).

“These findings suggest that macroangiopathic and microangiopathic thrombosis may be the key pathologic process for myocardial injury in COVID-19 survivors,” the authors conclude.

Dr. Greenwood added, “We are currently analyzing the 6-month follow-up CMR scans, the quality-of-life questionnaires, and the 6-minute walk tests. These will give us great understanding of how the heart repairs after acute myocardial injury associated with COVID-19. It will also allow us to assess the impact on patient quality of life and functional capacity.”
 

‘Tour de force’

James A. de Lemos, MD, co-chair of the American Heart Association’s COVID-19 CVD Registry Steering Committee and a professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said, “This is a tour de force collaboration – obtaining this many MRIs across multiple centers in the pandemic is quite remarkable. The study highlights the multiple different processes that lead to cardiac injury in COVID patients, complements autopsy studies and prior smaller MRI studies, [and] also provides the best data on the rate of myocarditis to date among the subset of COVID patients with cardiac injury.”

Overall, he said, the findings “do support closer follow-up for patients who had COVID and elevated troponins. We need to see follow-up MRI results in this cohort, as well as longer term outcomes. We also need studies on newer, more benign variants that are likely to have lower rates of cardiac injury and even fewer MRI abnormalities.”

Matthias Stuber, PhD, and Aaron L. Baggish, MD, both of Lausanne University Hospital and University of Lausanne, Switzerland, noted in a related editorial, “We are also reminded that the clinical severity of COVID-19 is most often dictated by the presence of pre-existing comorbidity, with antecedent ischemic scar now added to the long list of bad actors. Although not the primary focus of the COVID-HEART study, the question of whether cardiac troponin levels should be checked routinely and universally during the index admission for COVID-19 remains unresolved,” they noted.

“In general, we are most effective as clinicians when we use tests to confirm or rule out the specific disease processes suspected by careful basic clinical assessment rather than in a shotgun manner among undifferentiated all-comers,” they conclude.

No commercial funding or relevant financial relationships were reported.

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

About two-thirds of people with type 1 diabetes in the United States have overweight or obesity, nearly the same proportion as Americans without diabetes, new nationwide survey data suggest.

What’s more, among people with overweight or obesity, those with type 1 diabetes are less likely to receive lifestyle recommendations from health care professionals than those with type 2 diabetes, and are less likely to actually engage in lifestyle weight management activities than others with overweight or obesity, with or without type 2 diabetes.

“Among U.S. adults with type 1 diabetes, the burden of overweight and obesity is substantial and remains poorly managed,” write Michael Fang, PhD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues.

Their data, from the National Health Interview Survey (NHIS), were published online in Annals of Internal Medicine.

The need for insulin complicates weight management in people with type 1 diabetes because changes in diet and physical activity typically require adjustments to insulin timing and dosage to prevent hypoglycemia. There is little evidence to guide this for weight management, Dr. Fang and colleagues explain.

Consequently, “the lack of evidence for safe, effective methods of diet- and exercise-based weight control in people with type 1 diabetes may be keeping doctors from recommending such methods,” Dr. Fang said in a statement.

“Large clinical trials have been done in type 2 diabetes patients to establish guidelines for diet- and exercise-based weight management, and we now need something similar for type 1 diabetes patients.”  

Asked to comment, M. Sue Kirkman, MD, told this news organization: “The days when we could teach simple concepts about diabetes type like ‘those with type 1 are lean and those with type 2 are overweight’ are long gone. … Of concern, fewer adults with type 1 diabetes and overweight/obesity report that they are engaging in physical activity or caloric restriction than those without diabetes or those with type 2 diabetes.”

There are several likely reasons for the low rates of obesity/overweight lifestyle modification advice and implementation for those with type 1 diabetes, noted Dr. Kirkman, of the University of North Carolina at Chapel Hill, who coauthored joint American/European guidance on type 1 diabetes management.

“Medical visits are often primarily focused on glycemic management and complications screening, and we know that physicians in general are not very knowledgeable about how to counsel people – even those without diabetes – on weight loss. When you add in potential worries, real or not, about hypoglycemia, ketosis with carbohydrate restriction … it’s no wonder that this may not be addressed in busy visits.”

She also observed, “In years of going to diabetes meetings, I’ve noticed occasional sessions on managing ‘elite athletes’ with type 1 diabetes, but rarely are there sessions on how to counsel people about everyday healthy living.”
 

Many with type 1 diabetes have overweight/obesity

Dr. Fang and colleagues analyzed NHIS data for the years 2016, 2017, 2019, 2020, and 2021, when diabetes subtype data were available, for 128,571 adults. Diabetes type and height/weight data were self-reported. In the 2016, 2017, and 2020 surveys, participants were asked whether their physicians had recommended increasing physical activity and/or reducing calorie or fat consumption, and whether they were currently engaging in those activities.

The study population comprised 733 people with type 1 diabetes, 12,397 with type 2 diabetes, and 115,441 without diabetes. The proportions with overweight (body mass index, 25 to < 30 kg/m²) or obesity (≥ 30 kg/m²) were 62% among those with type 1 diabetes and 64% among those without diabetes, compared with 86% among those with type 2 diabetes.

Among those with overweight or obesity, the proportions who reported having received lifestyle recommendations were greatest among those with type 2 diabetes and least among those without diabetes, with the type 1 diabetes group in the middle.

After adjustment for age, sex, and race/ethnicity, the adjusted prevalence of receiving a provider recommendation to increase physical activity was 60% for those with type 2 diabetes, 54% for type 1 diabetes, and 44% for those without diabetes. Proportions for receiving recommendations for reducing fat/caloric intake were similar, at 60%, 51%, and 41%, respectively.

The proportions who reported actually engaging in lifestyle activities for weight management were lowest among those with type 1 diabetes, with 52% and 56% of them reporting having increased their physical activity and reducing fat/calories, respectively, compared with proportions ranging from 56% to 63% among the other two groups.

Regarding those findings, Dr. Kirkman commented, “In addition to the factors regarding physician interactions, people with type 1 diabetes may see this as a lower-priority health issue after years of being told that glucose control is the main priority.”

“I also wonder if the many, many tasks people with type 1 diabetes must do every day to manage their diabetes – along with other life issues all adults face – mean that there is just too much on the plate to add more lifestyle changes,” she added.

Asked about the potential for off-label use of glucagonlike peptide–1 agonists for weight management for people with type 1 diabetes, Dr. Kirkman said they could probably help some patients. However, she also pointed to two clinical trials in which liraglutide added to insulin therapy helped with glycemic control and weight reduction, but also increased the risk for hypoglycemia and diabetic ketoacidosis.

“It’s really important that researchers engage with adults with type 1 diabetes to better understand the unique priorities and barriers they face in addressing body weight,” Dr. Kirkman said.

Senior study author Elizabeth Selvin, PhD, professor of epidemiology at the Bloomberg School, said in the statement: “Our study busts the myth that people with type 1 diabetes are not being affected by the global obesity epidemic. … These findings should be a wake-up call that we need to be aggressive in addressing the obesity epidemic in persons with type 1 diabetes.”

The study was funded by the U.S. National Institutes of Health. Dr. Fang and Dr. Kirkman have reported no relevant financial relationships. Dr. Selvin has reported receiving royalty payments from Wolters Kluwer for chapters and laboratory monographs in UpToDate. She also reports receiving honoraria for editorial work on journals published by the American Diabetes Association and European Association for the Study of Diabetes.

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

About two-thirds of people with type 1 diabetes in the United States have overweight or obesity, nearly the same proportion as Americans without diabetes, new nationwide survey data suggest.

What’s more, among people with overweight or obesity, those with type 1 diabetes are less likely to receive lifestyle recommendations from health care professionals than those with type 2 diabetes, and are less likely to actually engage in lifestyle weight management activities than others with overweight or obesity, with or without type 2 diabetes.

“Among U.S. adults with type 1 diabetes, the burden of overweight and obesity is substantial and remains poorly managed,” write Michael Fang, PhD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues.

Their data, from the National Health Interview Survey (NHIS), were published online in Annals of Internal Medicine.

The need for insulin complicates weight management in people with type 1 diabetes because changes in diet and physical activity typically require adjustments to insulin timing and dosage to prevent hypoglycemia. There is little evidence to guide this for weight management, Dr. Fang and colleagues explain.

Consequently, “the lack of evidence for safe, effective methods of diet- and exercise-based weight control in people with type 1 diabetes may be keeping doctors from recommending such methods,” Dr. Fang said in a statement.

“Large clinical trials have been done in type 2 diabetes patients to establish guidelines for diet- and exercise-based weight management, and we now need something similar for type 1 diabetes patients.”  

Asked to comment, M. Sue Kirkman, MD, told this news organization: “The days when we could teach simple concepts about diabetes type like ‘those with type 1 are lean and those with type 2 are overweight’ are long gone. … Of concern, fewer adults with type 1 diabetes and overweight/obesity report that they are engaging in physical activity or caloric restriction than those without diabetes or those with type 2 diabetes.”

There are several likely reasons for the low rates of obesity/overweight lifestyle modification advice and implementation for those with type 1 diabetes, noted Dr. Kirkman, of the University of North Carolina at Chapel Hill, who coauthored joint American/European guidance on type 1 diabetes management.

“Medical visits are often primarily focused on glycemic management and complications screening, and we know that physicians in general are not very knowledgeable about how to counsel people – even those without diabetes – on weight loss. When you add in potential worries, real or not, about hypoglycemia, ketosis with carbohydrate restriction … it’s no wonder that this may not be addressed in busy visits.”

She also observed, “In years of going to diabetes meetings, I’ve noticed occasional sessions on managing ‘elite athletes’ with type 1 diabetes, but rarely are there sessions on how to counsel people about everyday healthy living.”
 

Many with type 1 diabetes have overweight/obesity

Dr. Fang and colleagues analyzed NHIS data for the years 2016, 2017, 2019, 2020, and 2021, when diabetes subtype data were available, for 128,571 adults. Diabetes type and height/weight data were self-reported. In the 2016, 2017, and 2020 surveys, participants were asked whether their physicians had recommended increasing physical activity and/or reducing calorie or fat consumption, and whether they were currently engaging in those activities.

The study population comprised 733 people with type 1 diabetes, 12,397 with type 2 diabetes, and 115,441 without diabetes. The proportions with overweight (body mass index, 25 to < 30 kg/m²) or obesity (≥ 30 kg/m²) were 62% among those with type 1 diabetes and 64% among those without diabetes, compared with 86% among those with type 2 diabetes.

Among those with overweight or obesity, the proportions who reported having received lifestyle recommendations were greatest among those with type 2 diabetes and least among those without diabetes, with the type 1 diabetes group in the middle.

After adjustment for age, sex, and race/ethnicity, the adjusted prevalence of receiving a provider recommendation to increase physical activity was 60% for those with type 2 diabetes, 54% for type 1 diabetes, and 44% for those without diabetes. Proportions for receiving recommendations for reducing fat/caloric intake were similar, at 60%, 51%, and 41%, respectively.

The proportions who reported actually engaging in lifestyle activities for weight management were lowest among those with type 1 diabetes, with 52% and 56% of them reporting having increased their physical activity and reducing fat/calories, respectively, compared with proportions ranging from 56% to 63% among the other two groups.

Regarding those findings, Dr. Kirkman commented, “In addition to the factors regarding physician interactions, people with type 1 diabetes may see this as a lower-priority health issue after years of being told that glucose control is the main priority.”

“I also wonder if the many, many tasks people with type 1 diabetes must do every day to manage their diabetes – along with other life issues all adults face – mean that there is just too much on the plate to add more lifestyle changes,” she added.

Asked about the potential for off-label use of glucagonlike peptide–1 agonists for weight management for people with type 1 diabetes, Dr. Kirkman said they could probably help some patients. However, she also pointed to two clinical trials in which liraglutide added to insulin therapy helped with glycemic control and weight reduction, but also increased the risk for hypoglycemia and diabetic ketoacidosis.

“It’s really important that researchers engage with adults with type 1 diabetes to better understand the unique priorities and barriers they face in addressing body weight,” Dr. Kirkman said.

Senior study author Elizabeth Selvin, PhD, professor of epidemiology at the Bloomberg School, said in the statement: “Our study busts the myth that people with type 1 diabetes are not being affected by the global obesity epidemic. … These findings should be a wake-up call that we need to be aggressive in addressing the obesity epidemic in persons with type 1 diabetes.”

The study was funded by the U.S. National Institutes of Health. Dr. Fang and Dr. Kirkman have reported no relevant financial relationships. Dr. Selvin has reported receiving royalty payments from Wolters Kluwer for chapters and laboratory monographs in UpToDate. She also reports receiving honoraria for editorial work on journals published by the American Diabetes Association and European Association for the Study of Diabetes.

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

About two-thirds of people with type 1 diabetes in the United States have overweight or obesity, nearly the same proportion as Americans without diabetes, new nationwide survey data suggest.

What’s more, among people with overweight or obesity, those with type 1 diabetes are less likely to receive lifestyle recommendations from health care professionals than those with type 2 diabetes, and are less likely to actually engage in lifestyle weight management activities than others with overweight or obesity, with or without type 2 diabetes.

“Among U.S. adults with type 1 diabetes, the burden of overweight and obesity is substantial and remains poorly managed,” write Michael Fang, PhD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues.

Their data, from the National Health Interview Survey (NHIS), were published online in Annals of Internal Medicine.

The need for insulin complicates weight management in people with type 1 diabetes because changes in diet and physical activity typically require adjustments to insulin timing and dosage to prevent hypoglycemia. There is little evidence to guide this for weight management, Dr. Fang and colleagues explain.

Consequently, “the lack of evidence for safe, effective methods of diet- and exercise-based weight control in people with type 1 diabetes may be keeping doctors from recommending such methods,” Dr. Fang said in a statement.

“Large clinical trials have been done in type 2 diabetes patients to establish guidelines for diet- and exercise-based weight management, and we now need something similar for type 1 diabetes patients.”  

Asked to comment, M. Sue Kirkman, MD, told this news organization: “The days when we could teach simple concepts about diabetes type like ‘those with type 1 are lean and those with type 2 are overweight’ are long gone. … Of concern, fewer adults with type 1 diabetes and overweight/obesity report that they are engaging in physical activity or caloric restriction than those without diabetes or those with type 2 diabetes.”

There are several likely reasons for the low rates of obesity/overweight lifestyle modification advice and implementation for those with type 1 diabetes, noted Dr. Kirkman, of the University of North Carolina at Chapel Hill, who coauthored joint American/European guidance on type 1 diabetes management.

“Medical visits are often primarily focused on glycemic management and complications screening, and we know that physicians in general are not very knowledgeable about how to counsel people – even those without diabetes – on weight loss. When you add in potential worries, real or not, about hypoglycemia, ketosis with carbohydrate restriction … it’s no wonder that this may not be addressed in busy visits.”

She also observed, “In years of going to diabetes meetings, I’ve noticed occasional sessions on managing ‘elite athletes’ with type 1 diabetes, but rarely are there sessions on how to counsel people about everyday healthy living.”
 

Many with type 1 diabetes have overweight/obesity

Dr. Fang and colleagues analyzed NHIS data for the years 2016, 2017, 2019, 2020, and 2021, when diabetes subtype data were available, for 128,571 adults. Diabetes type and height/weight data were self-reported. In the 2016, 2017, and 2020 surveys, participants were asked whether their physicians had recommended increasing physical activity and/or reducing calorie or fat consumption, and whether they were currently engaging in those activities.

The study population comprised 733 people with type 1 diabetes, 12,397 with type 2 diabetes, and 115,441 without diabetes. The proportions with overweight (body mass index, 25 to < 30 kg/m²) or obesity (≥ 30 kg/m²) were 62% among those with type 1 diabetes and 64% among those without diabetes, compared with 86% among those with type 2 diabetes.

Among those with overweight or obesity, the proportions who reported having received lifestyle recommendations were greatest among those with type 2 diabetes and least among those without diabetes, with the type 1 diabetes group in the middle.

After adjustment for age, sex, and race/ethnicity, the adjusted prevalence of receiving a provider recommendation to increase physical activity was 60% for those with type 2 diabetes, 54% for type 1 diabetes, and 44% for those without diabetes. Proportions for receiving recommendations for reducing fat/caloric intake were similar, at 60%, 51%, and 41%, respectively.

The proportions who reported actually engaging in lifestyle activities for weight management were lowest among those with type 1 diabetes, with 52% and 56% of them reporting having increased their physical activity and reducing fat/calories, respectively, compared with proportions ranging from 56% to 63% among the other two groups.

Regarding those findings, Dr. Kirkman commented, “In addition to the factors regarding physician interactions, people with type 1 diabetes may see this as a lower-priority health issue after years of being told that glucose control is the main priority.”

“I also wonder if the many, many tasks people with type 1 diabetes must do every day to manage their diabetes – along with other life issues all adults face – mean that there is just too much on the plate to add more lifestyle changes,” she added.

Asked about the potential for off-label use of glucagonlike peptide–1 agonists for weight management for people with type 1 diabetes, Dr. Kirkman said they could probably help some patients. However, she also pointed to two clinical trials in which liraglutide added to insulin therapy helped with glycemic control and weight reduction, but also increased the risk for hypoglycemia and diabetic ketoacidosis.

“It’s really important that researchers engage with adults with type 1 diabetes to better understand the unique priorities and barriers they face in addressing body weight,” Dr. Kirkman said.

Senior study author Elizabeth Selvin, PhD, professor of epidemiology at the Bloomberg School, said in the statement: “Our study busts the myth that people with type 1 diabetes are not being affected by the global obesity epidemic. … These findings should be a wake-up call that we need to be aggressive in addressing the obesity epidemic in persons with type 1 diabetes.”

The study was funded by the U.S. National Institutes of Health. Dr. Fang and Dr. Kirkman have reported no relevant financial relationships. Dr. Selvin has reported receiving royalty payments from Wolters Kluwer for chapters and laboratory monographs in UpToDate. She also reports receiving honoraria for editorial work on journals published by the American Diabetes Association and European Association for the Study of Diabetes.

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

Friday, Feb. 10, 2023, marked the first time a patient told me they had used ChatGPT to answer a medical question. I’ve been reluctant to write about this super-buzzy new AI chatbot, but I am starting to think it is the real deal. Just how powerful is it? Well, ChatGPT might in fact be writing this column right now. It isn’t. No really, it’s me. But if not for the few cues (“super-buzzy”) that you’ll recognize as my writing voice, there might not be any way for you to know if I wrote this or not.

It’s perfectly OK if you’ve no clue what I’m talking about. ChatGPT is an AI chatbot that burst into public view just a couple months ago. Not your parent’s chatbot, this one is capable of answering questions in conversational language. It is jaw-droppingly good. Like Google, you can type in a question and it offers you answers. Rather than giving you a list of websites and a few Wikipedia blurbs, however, ChatGPT answers your question in human-like text. It can also create content on demand. For example, I asked it to write a Valentine poem to a dermatologist, and it gave me five stanzas starting with:

Oh gentle healer of skin so fair,
Your touch is soft and hands so rare,
With your skills and gentle care,
You make my heart skip with a flare.

Not good enough to send to my wife. But not bad.

If you ask it again, it will create a whole new one for you. Amusing, yes? What if you asked ChatGPT to explain psoriasis, or any medical condition for that matter, to a patient? The replies are quite good. Some even better than what I’m currently using for my patients. It can also offer treatment recommendations, vacation advice, and plan, with recipes, a dinner party for six with one vegan and one gluten-free couple. If you are a programmer, it can write code. Ask it for a Wordpress plugin to add to your website and your eyes will widen as you see it magically appear before you. What if you find that you just don’t like your daughter’s new boyfriend? Yep, it will write the text or email for you to help with this discussion. I’ve saved that one.

I tried “What are treatments for bullous pemphigoid that has been refractory to topical steroid, oral prednisone, and oral tetracyclines?” It replied with five ideas, including the standard methotrexate and azathioprine but also IVIG, Rituxan, even other biologics. Write an op note? Appeal a denied prior authorization to a payer? Write a clinic note for a complete skin exam? Check, check, check. Are you starting to think it might be the real deal, too?

Before we sell the farm though, there are significant limitations. Despite how swotty ChatGPT seems, it is not smart. That is, “it” has no idea what “it” is saying. ChatGPT is an incredibly sophisticated algorithm that has learned the probability of what word comes next in a conversation. To do so, it read the Internet. Billions (trillions?) of words make it possible to predict what is the best answer to any question. But – it’s only as good as the Internet, so there’s that. My patient who used ChatGPT has dissecting cellulitis and asked what to do for scarring alopecia. Some of the answers were reasonable, but some, such as transplanting hairs into the scarred areas, would not likely be helpful. That is unless ChatGPT knows something I don’t.

Having wasted hours of time playing with this thing rather than writing my column, I asked ChatGPT to write an article about itself in the style of Christopher Hitchens. It was nothing like his incisive and eloquent prose, but it wrote 500 words in a few seconds ending with:

“The reality is that there is no substitute for human interaction and empathy in the field of dermatology. Dermatologists must be cautious in their adoption of ChatGPT and ensure that they are not sacrificing the quality of patient care in the pursuit of efficiency and convenience.”

I’m not sure I could have said it better myself.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

Friday, Feb. 10, 2023, marked the first time a patient told me they had used ChatGPT to answer a medical question. I’ve been reluctant to write about this super-buzzy new AI chatbot, but I am starting to think it is the real deal. Just how powerful is it? Well, ChatGPT might in fact be writing this column right now. It isn’t. No really, it’s me. But if not for the few cues (“super-buzzy”) that you’ll recognize as my writing voice, there might not be any way for you to know if I wrote this or not.

It’s perfectly OK if you’ve no clue what I’m talking about. ChatGPT is an AI chatbot that burst into public view just a couple months ago. Not your parent’s chatbot, this one is capable of answering questions in conversational language. It is jaw-droppingly good. Like Google, you can type in a question and it offers you answers. Rather than giving you a list of websites and a few Wikipedia blurbs, however, ChatGPT answers your question in human-like text. It can also create content on demand. For example, I asked it to write a Valentine poem to a dermatologist, and it gave me five stanzas starting with:

Oh gentle healer of skin so fair,
Your touch is soft and hands so rare,
With your skills and gentle care,
You make my heart skip with a flare.

Not good enough to send to my wife. But not bad.

If you ask it again, it will create a whole new one for you. Amusing, yes? What if you asked ChatGPT to explain psoriasis, or any medical condition for that matter, to a patient? The replies are quite good. Some even better than what I’m currently using for my patients. It can also offer treatment recommendations, vacation advice, and plan, with recipes, a dinner party for six with one vegan and one gluten-free couple. If you are a programmer, it can write code. Ask it for a Wordpress plugin to add to your website and your eyes will widen as you see it magically appear before you. What if you find that you just don’t like your daughter’s new boyfriend? Yep, it will write the text or email for you to help with this discussion. I’ve saved that one.

I tried “What are treatments for bullous pemphigoid that has been refractory to topical steroid, oral prednisone, and oral tetracyclines?” It replied with five ideas, including the standard methotrexate and azathioprine but also IVIG, Rituxan, even other biologics. Write an op note? Appeal a denied prior authorization to a payer? Write a clinic note for a complete skin exam? Check, check, check. Are you starting to think it might be the real deal, too?

Before we sell the farm though, there are significant limitations. Despite how swotty ChatGPT seems, it is not smart. That is, “it” has no idea what “it” is saying. ChatGPT is an incredibly sophisticated algorithm that has learned the probability of what word comes next in a conversation. To do so, it read the Internet. Billions (trillions?) of words make it possible to predict what is the best answer to any question. But – it’s only as good as the Internet, so there’s that. My patient who used ChatGPT has dissecting cellulitis and asked what to do for scarring alopecia. Some of the answers were reasonable, but some, such as transplanting hairs into the scarred areas, would not likely be helpful. That is unless ChatGPT knows something I don’t.

Having wasted hours of time playing with this thing rather than writing my column, I asked ChatGPT to write an article about itself in the style of Christopher Hitchens. It was nothing like his incisive and eloquent prose, but it wrote 500 words in a few seconds ending with:

“The reality is that there is no substitute for human interaction and empathy in the field of dermatology. Dermatologists must be cautious in their adoption of ChatGPT and ensure that they are not sacrificing the quality of patient care in the pursuit of efficiency and convenience.”

I’m not sure I could have said it better myself.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

Friday, Feb. 10, 2023, marked the first time a patient told me they had used ChatGPT to answer a medical question. I’ve been reluctant to write about this super-buzzy new AI chatbot, but I am starting to think it is the real deal. Just how powerful is it? Well, ChatGPT might in fact be writing this column right now. It isn’t. No really, it’s me. But if not for the few cues (“super-buzzy”) that you’ll recognize as my writing voice, there might not be any way for you to know if I wrote this or not.

It’s perfectly OK if you’ve no clue what I’m talking about. ChatGPT is an AI chatbot that burst into public view just a couple months ago. Not your parent’s chatbot, this one is capable of answering questions in conversational language. It is jaw-droppingly good. Like Google, you can type in a question and it offers you answers. Rather than giving you a list of websites and a few Wikipedia blurbs, however, ChatGPT answers your question in human-like text. It can also create content on demand. For example, I asked it to write a Valentine poem to a dermatologist, and it gave me five stanzas starting with:

Oh gentle healer of skin so fair,
Your touch is soft and hands so rare,
With your skills and gentle care,
You make my heart skip with a flare.

Not good enough to send to my wife. But not bad.

If you ask it again, it will create a whole new one for you. Amusing, yes? What if you asked ChatGPT to explain psoriasis, or any medical condition for that matter, to a patient? The replies are quite good. Some even better than what I’m currently using for my patients. It can also offer treatment recommendations, vacation advice, and plan, with recipes, a dinner party for six with one vegan and one gluten-free couple. If you are a programmer, it can write code. Ask it for a Wordpress plugin to add to your website and your eyes will widen as you see it magically appear before you. What if you find that you just don’t like your daughter’s new boyfriend? Yep, it will write the text or email for you to help with this discussion. I’ve saved that one.

I tried “What are treatments for bullous pemphigoid that has been refractory to topical steroid, oral prednisone, and oral tetracyclines?” It replied with five ideas, including the standard methotrexate and azathioprine but also IVIG, Rituxan, even other biologics. Write an op note? Appeal a denied prior authorization to a payer? Write a clinic note for a complete skin exam? Check, check, check. Are you starting to think it might be the real deal, too?

Before we sell the farm though, there are significant limitations. Despite how swotty ChatGPT seems, it is not smart. That is, “it” has no idea what “it” is saying. ChatGPT is an incredibly sophisticated algorithm that has learned the probability of what word comes next in a conversation. To do so, it read the Internet. Billions (trillions?) of words make it possible to predict what is the best answer to any question. But – it’s only as good as the Internet, so there’s that. My patient who used ChatGPT has dissecting cellulitis and asked what to do for scarring alopecia. Some of the answers were reasonable, but some, such as transplanting hairs into the scarred areas, would not likely be helpful. That is unless ChatGPT knows something I don’t.

Having wasted hours of time playing with this thing rather than writing my column, I asked ChatGPT to write an article about itself in the style of Christopher Hitchens. It was nothing like his incisive and eloquent prose, but it wrote 500 words in a few seconds ending with:

“The reality is that there is no substitute for human interaction and empathy in the field of dermatology. Dermatologists must be cautious in their adoption of ChatGPT and ensure that they are not sacrificing the quality of patient care in the pursuit of efficiency and convenience.”

I’m not sure I could have said it better myself.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

I visited a legal cannabis dispensary in Massachusetts a few years ago, mostly to see what the hype was about. There I was, knowing basically nothing about pot, as the gentle stoner behind the counter explained to me the differences between the various strains. Acapulco Gold is buoyant and energizing; Purple Kush is sleepy, relaxed, dissociative. Here’s a strain that makes you feel nostalgic; here’s one that helps you focus. It was as complicated and as oddly specific as a fancy wine tasting – and, I had a feeling, about as reliable.

And while a strain that evokes memories of your first kiss is beyond the reach of modern cultivation practices, it is true that not all marijuana is created equal. It’s a plant, after all, and though delta-9-tetrahydrocannabinol (THC) is the chemical responsible for its euphoric effects, it is far from the only substance in there.

The second most important compound in cannabis is cannabidiol, and most people will tell you that CBD is the gentle yin to THC’s paranoiac yang. Hence your local ganja barista reminding you that, if you don›t want all those anxiety-inducing side effects of THC, grab a strain with a nice CBD balance.

Courtesy F. Perry Wilson, MD, MSCE

Courtesy F. Perry Wilson, MD, MSCE

Courtesy JAMA Network Open

Courtesy JAMA Network Open

Courtesy JAMA Network Open

Courtesy JAMA Network Open

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn.

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

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

I visited a legal cannabis dispensary in Massachusetts a few years ago, mostly to see what the hype was about. There I was, knowing basically nothing about pot, as the gentle stoner behind the counter explained to me the differences between the various strains. Acapulco Gold is buoyant and energizing; Purple Kush is sleepy, relaxed, dissociative. Here’s a strain that makes you feel nostalgic; here’s one that helps you focus. It was as complicated and as oddly specific as a fancy wine tasting – and, I had a feeling, about as reliable.

And while a strain that evokes memories of your first kiss is beyond the reach of modern cultivation practices, it is true that not all marijuana is created equal. It’s a plant, after all, and though delta-9-tetrahydrocannabinol (THC) is the chemical responsible for its euphoric effects, it is far from the only substance in there.

The second most important compound in cannabis is cannabidiol, and most people will tell you that CBD is the gentle yin to THC’s paranoiac yang. Hence your local ganja barista reminding you that, if you don›t want all those anxiety-inducing side effects of THC, grab a strain with a nice CBD balance.

Courtesy F. Perry Wilson, MD, MSCE

Courtesy F. Perry Wilson, MD, MSCE

Courtesy JAMA Network Open

Courtesy JAMA Network Open

Courtesy JAMA Network Open

Courtesy JAMA Network Open

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn.

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

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

I visited a legal cannabis dispensary in Massachusetts a few years ago, mostly to see what the hype was about. There I was, knowing basically nothing about pot, as the gentle stoner behind the counter explained to me the differences between the various strains. Acapulco Gold is buoyant and energizing; Purple Kush is sleepy, relaxed, dissociative. Here’s a strain that makes you feel nostalgic; here’s one that helps you focus. It was as complicated and as oddly specific as a fancy wine tasting – and, I had a feeling, about as reliable.

And while a strain that evokes memories of your first kiss is beyond the reach of modern cultivation practices, it is true that not all marijuana is created equal. It’s a plant, after all, and though delta-9-tetrahydrocannabinol (THC) is the chemical responsible for its euphoric effects, it is far from the only substance in there.

The second most important compound in cannabis is cannabidiol, and most people will tell you that CBD is the gentle yin to THC’s paranoiac yang. Hence your local ganja barista reminding you that, if you don›t want all those anxiety-inducing side effects of THC, grab a strain with a nice CBD balance.

Courtesy F. Perry Wilson, MD, MSCE

Courtesy F. Perry Wilson, MD, MSCE

Courtesy JAMA Network Open

Courtesy JAMA Network Open

Courtesy JAMA Network Open

Courtesy JAMA Network Open

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn.

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