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PHILADELPHIA — Gastrointestinal (GI) bleeding after percutaneous coronary intervention (PCI) among patients on dual antiplatelet therapy (DAPT) remains risky in terms of morbidity and mortality, but the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score could help predict that risk, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In a predominantly Hispanic population in Texas, 2.5% of post-PCI patients on DAPT had GI bleeding in the first year. The PRECISE-DAPT score helped to predict GI bleeding among high-risk and moderate-risk patients.

“Our study established that the PRECISE-DAPT score possesses a moderate predictive accuracy not only for overall bleeding risk but also specifically for gastrointestinal bleeding,” said lead author Jesus Guzman, MD, a gastroenterology fellow at the Texas Tech University Health Sciences Center El Paso.

Current guidelines from the American College of Cardiology and American Heart Association recommend DAPT for 6-12 months post-PCI, with consideration for shorter durations in patients with lower ischemic risks but higher bleeding risks.

“Interestingly, some of these patients were on DAPT for more than 2 years, which goes beyond the guidelines,” he said. “In this patient population, this has to do with them being lost to follow-up and getting reestablished, and they kept refilling their prescriptions.”

Guzman and colleagues conducted a retrospective cohort study of patients receiving DAPT after PCI from 2014 to 2021. They looked for GI bleeding rates at 1 year and across the duration of the study period, as well as endoscopic indications, findings, concurrent antiplatelet therapy, and the primary cause of bleeding.

In addition, the research team evaluated the predictive value of the PRECISE-DAPT score, which categorizes patients based on low risk (≤ 17), moderate risk (18-24), and high risk (≥ 25) for bleeding. The score aims to optimize the balance between bleeding and ischemic risks, Guzman said, by incorporating five factors: Age, creatinine clearance, hemoglobin, white blood cell count, and history of spontaneous bleeding.

Among 1067 patients, 563 (57.9%) received clopidogrel and 409 (42%) received ticagrelor. The overall cohort was 66.6% men, 77.1% Hispanic, and had a mean age of 62 years.

The GI bleeding rate was 2.5% at 1-year post-PCI among 27 patients and 3.7% for the study duration among 39 patients, with a median follow-up of 2.2 years.

Among the 39 GI bleeds, 41% were lower GI bleeds, 28% were upper GI bleeds, 15% were small bowel bleeds, and 15% were undetermined. The most frequent etiology was colon cancer, accounting for 18% of bleeds, followed by 15% for gastric ulcers, 10% for diverticular bleeds, and 10% for hemorrhoidal bleeds.

In general, analyses indicated no significant differences in GI bleeding between patients on clopidogrel (21.2%) and those on ticagrelor (19.2%).

However, the odds of GI bleeding were significantly higher in patients with high-risk PRECISE-DAPT scores (odds ratio [OR], 2.5) and moderate-risk scores (OR, 2.8) than in those with low-risk scores. The majority of patients without GI bleeding had scores < 17, whereas the majority of patients with GI bleeding had scores > 24. An optimal threshold for the PRECISE-DAPT score was identified as ≥ 19.

“When patients on DAPT present with GI bleeding, it can be a clinical conundrum for gastroenterologists and cardiologists, especially when it can be a life-or-death event, and stopping DAPT can increase risk of thrombosis,” said Jeff Taclob, MD, a hepatology fellow at The University of Tennessee Health Science Center in Memphis. Taclob, who wasn’t involved with the study, attended the conference session.

“In this population in El Paso, in particular, many patients don’t have adequate healthcare, may be lost to follow-up, and get their prescriptions filled elsewhere, such as Juárez, Mexico,” he said. “Then they come in with this life-threatening bleed, so we need to focus more on their risks.”

Paying attention to specific patient populations, cultures, and values remains important for patient communication and clinical decision-making, Taclob noted.

“In this population of older men, there’s often a macho persona where they don’t want to seek help,” he said. “DAPT criteria could differ in other populations, but here, the PRECISE-DAPT score appeared to help.”

The study was awarded the ACG Outstanding Research Award in the GI Bleeding Category (Trainee). Guzman and Taclob reported no relevant disclosures.

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

PHILADELPHIA — Gastrointestinal (GI) bleeding after percutaneous coronary intervention (PCI) among patients on dual antiplatelet therapy (DAPT) remains risky in terms of morbidity and mortality, but the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score could help predict that risk, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In a predominantly Hispanic population in Texas, 2.5% of post-PCI patients on DAPT had GI bleeding in the first year. The PRECISE-DAPT score helped to predict GI bleeding among high-risk and moderate-risk patients.

“Our study established that the PRECISE-DAPT score possesses a moderate predictive accuracy not only for overall bleeding risk but also specifically for gastrointestinal bleeding,” said lead author Jesus Guzman, MD, a gastroenterology fellow at the Texas Tech University Health Sciences Center El Paso.

Current guidelines from the American College of Cardiology and American Heart Association recommend DAPT for 6-12 months post-PCI, with consideration for shorter durations in patients with lower ischemic risks but higher bleeding risks.

“Interestingly, some of these patients were on DAPT for more than 2 years, which goes beyond the guidelines,” he said. “In this patient population, this has to do with them being lost to follow-up and getting reestablished, and they kept refilling their prescriptions.”

Guzman and colleagues conducted a retrospective cohort study of patients receiving DAPT after PCI from 2014 to 2021. They looked for GI bleeding rates at 1 year and across the duration of the study period, as well as endoscopic indications, findings, concurrent antiplatelet therapy, and the primary cause of bleeding.

In addition, the research team evaluated the predictive value of the PRECISE-DAPT score, which categorizes patients based on low risk (≤ 17), moderate risk (18-24), and high risk (≥ 25) for bleeding. The score aims to optimize the balance between bleeding and ischemic risks, Guzman said, by incorporating five factors: Age, creatinine clearance, hemoglobin, white blood cell count, and history of spontaneous bleeding.

Among 1067 patients, 563 (57.9%) received clopidogrel and 409 (42%) received ticagrelor. The overall cohort was 66.6% men, 77.1% Hispanic, and had a mean age of 62 years.

The GI bleeding rate was 2.5% at 1-year post-PCI among 27 patients and 3.7% for the study duration among 39 patients, with a median follow-up of 2.2 years.

Among the 39 GI bleeds, 41% were lower GI bleeds, 28% were upper GI bleeds, 15% were small bowel bleeds, and 15% were undetermined. The most frequent etiology was colon cancer, accounting for 18% of bleeds, followed by 15% for gastric ulcers, 10% for diverticular bleeds, and 10% for hemorrhoidal bleeds.

In general, analyses indicated no significant differences in GI bleeding between patients on clopidogrel (21.2%) and those on ticagrelor (19.2%).

However, the odds of GI bleeding were significantly higher in patients with high-risk PRECISE-DAPT scores (odds ratio [OR], 2.5) and moderate-risk scores (OR, 2.8) than in those with low-risk scores. The majority of patients without GI bleeding had scores < 17, whereas the majority of patients with GI bleeding had scores > 24. An optimal threshold for the PRECISE-DAPT score was identified as ≥ 19.

“When patients on DAPT present with GI bleeding, it can be a clinical conundrum for gastroenterologists and cardiologists, especially when it can be a life-or-death event, and stopping DAPT can increase risk of thrombosis,” said Jeff Taclob, MD, a hepatology fellow at The University of Tennessee Health Science Center in Memphis. Taclob, who wasn’t involved with the study, attended the conference session.

“In this population in El Paso, in particular, many patients don’t have adequate healthcare, may be lost to follow-up, and get their prescriptions filled elsewhere, such as Juárez, Mexico,” he said. “Then they come in with this life-threatening bleed, so we need to focus more on their risks.”

Paying attention to specific patient populations, cultures, and values remains important for patient communication and clinical decision-making, Taclob noted.

“In this population of older men, there’s often a macho persona where they don’t want to seek help,” he said. “DAPT criteria could differ in other populations, but here, the PRECISE-DAPT score appeared to help.”

The study was awarded the ACG Outstanding Research Award in the GI Bleeding Category (Trainee). Guzman and Taclob reported no relevant disclosures.

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

PHILADELPHIA — Gastrointestinal (GI) bleeding after percutaneous coronary intervention (PCI) among patients on dual antiplatelet therapy (DAPT) remains risky in terms of morbidity and mortality, but the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score could help predict that risk, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In a predominantly Hispanic population in Texas, 2.5% of post-PCI patients on DAPT had GI bleeding in the first year. The PRECISE-DAPT score helped to predict GI bleeding among high-risk and moderate-risk patients.

“Our study established that the PRECISE-DAPT score possesses a moderate predictive accuracy not only for overall bleeding risk but also specifically for gastrointestinal bleeding,” said lead author Jesus Guzman, MD, a gastroenterology fellow at the Texas Tech University Health Sciences Center El Paso.

Current guidelines from the American College of Cardiology and American Heart Association recommend DAPT for 6-12 months post-PCI, with consideration for shorter durations in patients with lower ischemic risks but higher bleeding risks.

“Interestingly, some of these patients were on DAPT for more than 2 years, which goes beyond the guidelines,” he said. “In this patient population, this has to do with them being lost to follow-up and getting reestablished, and they kept refilling their prescriptions.”

Guzman and colleagues conducted a retrospective cohort study of patients receiving DAPT after PCI from 2014 to 2021. They looked for GI bleeding rates at 1 year and across the duration of the study period, as well as endoscopic indications, findings, concurrent antiplatelet therapy, and the primary cause of bleeding.

In addition, the research team evaluated the predictive value of the PRECISE-DAPT score, which categorizes patients based on low risk (≤ 17), moderate risk (18-24), and high risk (≥ 25) for bleeding. The score aims to optimize the balance between bleeding and ischemic risks, Guzman said, by incorporating five factors: Age, creatinine clearance, hemoglobin, white blood cell count, and history of spontaneous bleeding.

Among 1067 patients, 563 (57.9%) received clopidogrel and 409 (42%) received ticagrelor. The overall cohort was 66.6% men, 77.1% Hispanic, and had a mean age of 62 years.

The GI bleeding rate was 2.5% at 1-year post-PCI among 27 patients and 3.7% for the study duration among 39 patients, with a median follow-up of 2.2 years.

Among the 39 GI bleeds, 41% were lower GI bleeds, 28% were upper GI bleeds, 15% were small bowel bleeds, and 15% were undetermined. The most frequent etiology was colon cancer, accounting for 18% of bleeds, followed by 15% for gastric ulcers, 10% for diverticular bleeds, and 10% for hemorrhoidal bleeds.

In general, analyses indicated no significant differences in GI bleeding between patients on clopidogrel (21.2%) and those on ticagrelor (19.2%).

However, the odds of GI bleeding were significantly higher in patients with high-risk PRECISE-DAPT scores (odds ratio [OR], 2.5) and moderate-risk scores (OR, 2.8) than in those with low-risk scores. The majority of patients without GI bleeding had scores < 17, whereas the majority of patients with GI bleeding had scores > 24. An optimal threshold for the PRECISE-DAPT score was identified as ≥ 19.

“When patients on DAPT present with GI bleeding, it can be a clinical conundrum for gastroenterologists and cardiologists, especially when it can be a life-or-death event, and stopping DAPT can increase risk of thrombosis,” said Jeff Taclob, MD, a hepatology fellow at The University of Tennessee Health Science Center in Memphis. Taclob, who wasn’t involved with the study, attended the conference session.

“In this population in El Paso, in particular, many patients don’t have adequate healthcare, may be lost to follow-up, and get their prescriptions filled elsewhere, such as Juárez, Mexico,” he said. “Then they come in with this life-threatening bleed, so we need to focus more on their risks.”

Paying attention to specific patient populations, cultures, and values remains important for patient communication and clinical decision-making, Taclob noted.

“In this population of older men, there’s often a macho persona where they don’t want to seek help,” he said. “DAPT criteria could differ in other populations, but here, the PRECISE-DAPT score appeared to help.”

The study was awarded the ACG Outstanding Research Award in the GI Bleeding Category (Trainee). Guzman and Taclob reported no relevant disclosures.

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

If the name of leukemia specialist Jorge Cortes, MD, appears any more often in PubMed, they’ll need to name a wing after him. 

Over 30 years, Cortes has led or coauthored hundreds of studies, including many trials of landmark drugs to treat chronic myeloid leukemia (CML). His work has helped transform CML into an often-survivable disease instead of one that took the lives of most patients within 5 years.

“It’s been remarkable to see the evolution in CML and to be part of that transition as a fellow, as faculty, and as leader of some of the trials,” said Cortes, who directs the Georgia Cancer Center at Augusta University. “I’m the luckiest person in the world.”

In an interview, Cortes talked about his youth in Mexico, his research path, and his close connections to cancer medicine in Latin America.

Q: You grew up in Mexico City. What was your family like?

A: “My father grew up very poor in a small town in Michoacán in the southwest part of Mexico. In Mexico City, he had a tiny grocery store in an old-fashioned market, and we were lower middle class.

One of the things I learned was to work hard. There’s nobody I know who worked as hard as my father. He opened his store every day of the year, [Mexican] Independence Day or New Year’s or Christmas. He worked hard so we could have a better life than he did.

We learned English from a very young age. My elementary school was called Westminster School because he wanted a school where we would learn English.

As for my mother, she stayed with us [at home] and made sure we did our homework and were taken care of. I learned about being honest and dedicating to what you were doing.”

Q: You trained at the Salvador Zubirán National Institute of Health Sciences and Nutrition in Mexico City. Then what happened? 

A: “Through encouragement by my dermatologist older brother and a mentor at the institution where I was training as a hematologist, I decided to come to the United States.

My initial focus was going to be on coagulation and thrombosis. I came to Houston (Texas) for a fellowship at the University of Texas Health Science Center.

Then I started doing my rotation for the malignant part of the fellowship at MD Anderson Cancer Center [Houston]. One of my first rotations was with Susan M. O’Brien, [MD,] who became my greatest mentor throughout my career. I really enjoyed my rotation. I thought she was great clinically, and she was doing research and teaching. That’s what I wanted for my career.”

Q: What drew you to leukemia specifically?

A: “Dr O’Brien worked in leukemia during my initial rotation, and I really loved it. It was hard work, but it was very inspiring to see the clinical research and the things you could for patients. She had a lot of joy doing that. 

I told my program director I’d change and transfer to MD Anderson, and I ended up staying at MD Anderson for 23 years.”

Q: What was leukemia research like in those days?

A: “We didn’t have the understanding of the biology and the new drugs that we have now. When I started in Mexico, we didn’t even have hydroxyurea. What we were doing was much more basic. But still, the field sounded like a great field to be involved with because they were doing so many trials and had an outstanding database. 

Because of the influence of Dr [Moshe] Talpaz, [MD,] I started getting very involved with CML. In my initial years as a young faculty, I started working with him on interferon. Then imatinib appeared. I saw even from the phase 1 study how impressive the outcomes were in patients who had no response to anything and were in bad shape.”

Q: What CML medications have you worked on?

A: “I’ve been involved with all of them. Imatinib early on, then I led trials with dasatinib and nilotinib. Then, I led the registration trials of bosutinib and ponatinib. More recently, I was part of the development of asciminib.”

Q: What were some of the biggest challenges in CML research?

A: “We had an opportunity to do a lot of analysis about TKIs [tyrosine kinase inhibitors] when these were new drugs. It was a very steep curve of learning, how to monitor and manage side effects.

Then patients were starting to have resistance to two to three TKIs. Ponatinib came along, and it was an incredibly effective drug. But after it was approved, we started to recognize the occurrence of heart attacks and strokes.

That was unexpected and not something that was known for any TKI. It was a big challenge. The drug was taken off the market for some time, and trials were put on hold by the FDA [US Food and Drug Administration].

We scrambled to understand the mechanism of action. For a year or two, it was a stressful time. But eventually we moved past it, and we learned a lot.”

Q: What sort of work have you done in Latin America?

A: “I’ve always been very close to Latin America. I have many good friends and colleagues there, and I’ve always been interested in working with them. 

We’ve done research and studies and created an organization called Latin American Leukemia Net to develop more trials in Latin America. The most rewarding thing has been the educational programs for patients that we’ve done, helping them understand the disease, the treatments, and the goals of treatment. 

We’ve conducted a number of programs, and they have been effective, well-attended, and well received. I still work with my colleagues to develop local guidelines and do collaborative research.”

Q: What convinced you to leave MD Anderson for Georgia?

A: “I never thought I’d leave MD Anderson. I had my well-oiled machine of clinical trials, my clinic, and my fellowship program. But the one thing that I wanted to see if I could try next was to develop an institution.

That was the goal here, to take the Georgia Cancer Center to NCI [National Cancer Institute] designation. So, I thought, ‘That’s a nice challenge.’ It may be a good opportunity to try a different aspect of what it means to be an oncologist.

There are days that you think, ‘What am I doing here?’ when you have to deal with budgets and personnel and all these things. But it’s part of the process. It’s still good to know that we have a goal, and that we’re going to make it. 

Also, I still see my patients, and I enjoy that I still do some research and mentoring.”

Q: What’s the current state of CML treatment?

A: “Many patients have a pretty much normal life expectancy while [on therapy]. Still, one of the goals of many patients is to stop therapy. But that’s a reality only for a small percentage of patients. How can we make that happen for more patients?”

Q: By stopping therapy, do you mean curing the cancer?

A: “Yes, pretty much. You have a good response, you stop the therapy, and it doesn’t come back.

There are also patients who really don’t do well. We hear about CML being with a disease with such a good outcome, but we have patients for whom nothing works. Is it a matter of [needing] another TKI, or do we need to look at something else?”

Q: What do you see on the horizon?

A: “We are developing new approaches like combination therapies. We’re scratching the surface on that. We need to understand which combinations work, and where and when.

And we can make more efficient uses of the drugs we have now in terms of which ones to use when, the doses, the safety profiles. I think we can do better.”

Cortes disclosed consulting for Amphivena, Astellas, Bio-Path, BioLineRx, Bristol Myers Squibb, Daiichi Sankyo, Jazz, Novartis, Pfizer, and Takeda and research funding from Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Immunogen, Jazz, Merus, Novartis, Pfizer, Sun Pharma, Takeda, Tolero and Trovagene.
 

A version of this article appeared on Medscape.com.

If the name of leukemia specialist Jorge Cortes, MD, appears any more often in PubMed, they’ll need to name a wing after him. 

Over 30 years, Cortes has led or coauthored hundreds of studies, including many trials of landmark drugs to treat chronic myeloid leukemia (CML). His work has helped transform CML into an often-survivable disease instead of one that took the lives of most patients within 5 years.

“It’s been remarkable to see the evolution in CML and to be part of that transition as a fellow, as faculty, and as leader of some of the trials,” said Cortes, who directs the Georgia Cancer Center at Augusta University. “I’m the luckiest person in the world.”

In an interview, Cortes talked about his youth in Mexico, his research path, and his close connections to cancer medicine in Latin America.

Q: You grew up in Mexico City. What was your family like?

A: “My father grew up very poor in a small town in Michoacán in the southwest part of Mexico. In Mexico City, he had a tiny grocery store in an old-fashioned market, and we were lower middle class.

One of the things I learned was to work hard. There’s nobody I know who worked as hard as my father. He opened his store every day of the year, [Mexican] Independence Day or New Year’s or Christmas. He worked hard so we could have a better life than he did.

We learned English from a very young age. My elementary school was called Westminster School because he wanted a school where we would learn English.

As for my mother, she stayed with us [at home] and made sure we did our homework and were taken care of. I learned about being honest and dedicating to what you were doing.”

Q: You trained at the Salvador Zubirán National Institute of Health Sciences and Nutrition in Mexico City. Then what happened? 

A: “Through encouragement by my dermatologist older brother and a mentor at the institution where I was training as a hematologist, I decided to come to the United States.

My initial focus was going to be on coagulation and thrombosis. I came to Houston (Texas) for a fellowship at the University of Texas Health Science Center.

Then I started doing my rotation for the malignant part of the fellowship at MD Anderson Cancer Center [Houston]. One of my first rotations was with Susan M. O’Brien, [MD,] who became my greatest mentor throughout my career. I really enjoyed my rotation. I thought she was great clinically, and she was doing research and teaching. That’s what I wanted for my career.”

Q: What drew you to leukemia specifically?

A: “Dr O’Brien worked in leukemia during my initial rotation, and I really loved it. It was hard work, but it was very inspiring to see the clinical research and the things you could for patients. She had a lot of joy doing that. 

I told my program director I’d change and transfer to MD Anderson, and I ended up staying at MD Anderson for 23 years.”

Q: What was leukemia research like in those days?

A: “We didn’t have the understanding of the biology and the new drugs that we have now. When I started in Mexico, we didn’t even have hydroxyurea. What we were doing was much more basic. But still, the field sounded like a great field to be involved with because they were doing so many trials and had an outstanding database. 

Because of the influence of Dr [Moshe] Talpaz, [MD,] I started getting very involved with CML. In my initial years as a young faculty, I started working with him on interferon. Then imatinib appeared. I saw even from the phase 1 study how impressive the outcomes were in patients who had no response to anything and were in bad shape.”

Q: What CML medications have you worked on?

A: “I’ve been involved with all of them. Imatinib early on, then I led trials with dasatinib and nilotinib. Then, I led the registration trials of bosutinib and ponatinib. More recently, I was part of the development of asciminib.”

Q: What were some of the biggest challenges in CML research?

A: “We had an opportunity to do a lot of analysis about TKIs [tyrosine kinase inhibitors] when these were new drugs. It was a very steep curve of learning, how to monitor and manage side effects.

Then patients were starting to have resistance to two to three TKIs. Ponatinib came along, and it was an incredibly effective drug. But after it was approved, we started to recognize the occurrence of heart attacks and strokes.

That was unexpected and not something that was known for any TKI. It was a big challenge. The drug was taken off the market for some time, and trials were put on hold by the FDA [US Food and Drug Administration].

We scrambled to understand the mechanism of action. For a year or two, it was a stressful time. But eventually we moved past it, and we learned a lot.”

Q: What sort of work have you done in Latin America?

A: “I’ve always been very close to Latin America. I have many good friends and colleagues there, and I’ve always been interested in working with them. 

We’ve done research and studies and created an organization called Latin American Leukemia Net to develop more trials in Latin America. The most rewarding thing has been the educational programs for patients that we’ve done, helping them understand the disease, the treatments, and the goals of treatment. 

We’ve conducted a number of programs, and they have been effective, well-attended, and well received. I still work with my colleagues to develop local guidelines and do collaborative research.”

Q: What convinced you to leave MD Anderson for Georgia?

A: “I never thought I’d leave MD Anderson. I had my well-oiled machine of clinical trials, my clinic, and my fellowship program. But the one thing that I wanted to see if I could try next was to develop an institution.

That was the goal here, to take the Georgia Cancer Center to NCI [National Cancer Institute] designation. So, I thought, ‘That’s a nice challenge.’ It may be a good opportunity to try a different aspect of what it means to be an oncologist.

There are days that you think, ‘What am I doing here?’ when you have to deal with budgets and personnel and all these things. But it’s part of the process. It’s still good to know that we have a goal, and that we’re going to make it. 

Also, I still see my patients, and I enjoy that I still do some research and mentoring.”

Q: What’s the current state of CML treatment?

A: “Many patients have a pretty much normal life expectancy while [on therapy]. Still, one of the goals of many patients is to stop therapy. But that’s a reality only for a small percentage of patients. How can we make that happen for more patients?”

Q: By stopping therapy, do you mean curing the cancer?

A: “Yes, pretty much. You have a good response, you stop the therapy, and it doesn’t come back.

There are also patients who really don’t do well. We hear about CML being with a disease with such a good outcome, but we have patients for whom nothing works. Is it a matter of [needing] another TKI, or do we need to look at something else?”

Q: What do you see on the horizon?

A: “We are developing new approaches like combination therapies. We’re scratching the surface on that. We need to understand which combinations work, and where and when.

And we can make more efficient uses of the drugs we have now in terms of which ones to use when, the doses, the safety profiles. I think we can do better.”

Cortes disclosed consulting for Amphivena, Astellas, Bio-Path, BioLineRx, Bristol Myers Squibb, Daiichi Sankyo, Jazz, Novartis, Pfizer, and Takeda and research funding from Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Immunogen, Jazz, Merus, Novartis, Pfizer, Sun Pharma, Takeda, Tolero and Trovagene.
 

A version of this article appeared on Medscape.com.

If the name of leukemia specialist Jorge Cortes, MD, appears any more often in PubMed, they’ll need to name a wing after him. 

Over 30 years, Cortes has led or coauthored hundreds of studies, including many trials of landmark drugs to treat chronic myeloid leukemia (CML). His work has helped transform CML into an often-survivable disease instead of one that took the lives of most patients within 5 years.

“It’s been remarkable to see the evolution in CML and to be part of that transition as a fellow, as faculty, and as leader of some of the trials,” said Cortes, who directs the Georgia Cancer Center at Augusta University. “I’m the luckiest person in the world.”

In an interview, Cortes talked about his youth in Mexico, his research path, and his close connections to cancer medicine in Latin America.

Q: You grew up in Mexico City. What was your family like?

A: “My father grew up very poor in a small town in Michoacán in the southwest part of Mexico. In Mexico City, he had a tiny grocery store in an old-fashioned market, and we were lower middle class.

One of the things I learned was to work hard. There’s nobody I know who worked as hard as my father. He opened his store every day of the year, [Mexican] Independence Day or New Year’s or Christmas. He worked hard so we could have a better life than he did.

We learned English from a very young age. My elementary school was called Westminster School because he wanted a school where we would learn English.

As for my mother, she stayed with us [at home] and made sure we did our homework and were taken care of. I learned about being honest and dedicating to what you were doing.”

Q: You trained at the Salvador Zubirán National Institute of Health Sciences and Nutrition in Mexico City. Then what happened? 

A: “Through encouragement by my dermatologist older brother and a mentor at the institution where I was training as a hematologist, I decided to come to the United States.

My initial focus was going to be on coagulation and thrombosis. I came to Houston (Texas) for a fellowship at the University of Texas Health Science Center.

Then I started doing my rotation for the malignant part of the fellowship at MD Anderson Cancer Center [Houston]. One of my first rotations was with Susan M. O’Brien, [MD,] who became my greatest mentor throughout my career. I really enjoyed my rotation. I thought she was great clinically, and she was doing research and teaching. That’s what I wanted for my career.”

Q: What drew you to leukemia specifically?

A: “Dr O’Brien worked in leukemia during my initial rotation, and I really loved it. It was hard work, but it was very inspiring to see the clinical research and the things you could for patients. She had a lot of joy doing that. 

I told my program director I’d change and transfer to MD Anderson, and I ended up staying at MD Anderson for 23 years.”

Q: What was leukemia research like in those days?

A: “We didn’t have the understanding of the biology and the new drugs that we have now. When I started in Mexico, we didn’t even have hydroxyurea. What we were doing was much more basic. But still, the field sounded like a great field to be involved with because they were doing so many trials and had an outstanding database. 

Because of the influence of Dr [Moshe] Talpaz, [MD,] I started getting very involved with CML. In my initial years as a young faculty, I started working with him on interferon. Then imatinib appeared. I saw even from the phase 1 study how impressive the outcomes were in patients who had no response to anything and were in bad shape.”

Q: What CML medications have you worked on?

A: “I’ve been involved with all of them. Imatinib early on, then I led trials with dasatinib and nilotinib. Then, I led the registration trials of bosutinib and ponatinib. More recently, I was part of the development of asciminib.”

Q: What were some of the biggest challenges in CML research?

A: “We had an opportunity to do a lot of analysis about TKIs [tyrosine kinase inhibitors] when these were new drugs. It was a very steep curve of learning, how to monitor and manage side effects.

Then patients were starting to have resistance to two to three TKIs. Ponatinib came along, and it was an incredibly effective drug. But after it was approved, we started to recognize the occurrence of heart attacks and strokes.

That was unexpected and not something that was known for any TKI. It was a big challenge. The drug was taken off the market for some time, and trials were put on hold by the FDA [US Food and Drug Administration].

We scrambled to understand the mechanism of action. For a year or two, it was a stressful time. But eventually we moved past it, and we learned a lot.”

Q: What sort of work have you done in Latin America?

A: “I’ve always been very close to Latin America. I have many good friends and colleagues there, and I’ve always been interested in working with them. 

We’ve done research and studies and created an organization called Latin American Leukemia Net to develop more trials in Latin America. The most rewarding thing has been the educational programs for patients that we’ve done, helping them understand the disease, the treatments, and the goals of treatment. 

We’ve conducted a number of programs, and they have been effective, well-attended, and well received. I still work with my colleagues to develop local guidelines and do collaborative research.”

Q: What convinced you to leave MD Anderson for Georgia?

A: “I never thought I’d leave MD Anderson. I had my well-oiled machine of clinical trials, my clinic, and my fellowship program. But the one thing that I wanted to see if I could try next was to develop an institution.

That was the goal here, to take the Georgia Cancer Center to NCI [National Cancer Institute] designation. So, I thought, ‘That’s a nice challenge.’ It may be a good opportunity to try a different aspect of what it means to be an oncologist.

There are days that you think, ‘What am I doing here?’ when you have to deal with budgets and personnel and all these things. But it’s part of the process. It’s still good to know that we have a goal, and that we’re going to make it. 

Also, I still see my patients, and I enjoy that I still do some research and mentoring.”

Q: What’s the current state of CML treatment?

A: “Many patients have a pretty much normal life expectancy while [on therapy]. Still, one of the goals of many patients is to stop therapy. But that’s a reality only for a small percentage of patients. How can we make that happen for more patients?”

Q: By stopping therapy, do you mean curing the cancer?

A: “Yes, pretty much. You have a good response, you stop the therapy, and it doesn’t come back.

There are also patients who really don’t do well. We hear about CML being with a disease with such a good outcome, but we have patients for whom nothing works. Is it a matter of [needing] another TKI, or do we need to look at something else?”

Q: What do you see on the horizon?

A: “We are developing new approaches like combination therapies. We’re scratching the surface on that. We need to understand which combinations work, and where and when.

And we can make more efficient uses of the drugs we have now in terms of which ones to use when, the doses, the safety profiles. I think we can do better.”

Cortes disclosed consulting for Amphivena, Astellas, Bio-Path, BioLineRx, Bristol Myers Squibb, Daiichi Sankyo, Jazz, Novartis, Pfizer, and Takeda and research funding from Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Immunogen, Jazz, Merus, Novartis, Pfizer, Sun Pharma, Takeda, Tolero and Trovagene.
 

A version of this article appeared on Medscape.com.

WASHINGTON — Colchicine does not protect against major cardiovascular adverse events after an acute myocardial infarction, according to a multinational placebo-controlled trial of more than 7000 patients.

The CLEAR SYNERGY (OASIS 9) study, called “the largest trial ever of colchicine in acute MI,” showed no hint of benefit in an adverse event curve for colchicine relative to placebo over 5 years, which suggests that the role of this drug after myocardial infarction (MI) “is uncertain,” Sanjit Jolly, MD, an interventional cardiologist at Hamilton Health Sciences and a professor of medicine at McMaster University in Hamilton, Ontario, Canada, reported at Transcatheter Cardiovascular Therapeutics (TCT) 2024.

For the primary composite outcome — cardiovascular death, MI, stroke, and ischemia-driven revascularization — the event curves in the colchicine and placebo groups remained essentially superimposed over 5 years of follow-up, with only a slight separation after 4 years. The hazard ratio for the primary endpoint showed a 1% difference in favor of colchicine (hazard ratio [HR], 0.99; P = .93).

There were no meaningful differences in any of the individual endpoint components; all 95% CIs straddled the line of unity. Rates of cardiovascular death (3.3% vs 3.2%) and stroke (1.4% vs 1.2%) were numerically higher in the colchicine group than in the placebo group. Rates of MI (2.9% vs 3.1%) and ischemia-driven revascularization (4.6% vs 4.7%) were numerically lower in the colchicine group.

 

No Difference

No adverse outcomes, including all-cause death (4.6% vs 5.1%), approached significance, with the exception of noncardiovascular death (13.0% vs 1.9%). For this outcome, the 95% CI stopped just short of the line of unity (HR, 0.68; 95% CI, 0.46-0.99).

Rates of adverse events (31.9% vs 31.7%; P = .86), serious adverse events (6.7% vs 7.4%; P = .22), and serious infections (2.5% vs 2.9%; P = .85) were similar in the colchicine and placebo groups, but diarrhea, a known side effect of colchicine, was higher in the colchicine group (10.2% vs 6.6%; P < .001).

Given these results, a panelist questioned the use of the word “uncertain” to describe the findings during the late-breaker session in which these results were presented.

“I think you are selling yourself short,” said J. Dawn Abbott, MD, director of the Interventional Cardiology Fellowship Training Program at the Lifespan Cardiovascular Institute, Brown University in Providence, Rhode Island. Based on the size and conduct of this trial, she called the results “definitive” and suggested that the guidelines should be adjusted.

 

The OASIS 9 Trial

In OASIS 9, 3528 patients were randomized to colchicine, and 3534 were randomized to placebo. A second randomization in both groups was to spironolactone or placebo; these results will be presented at the upcoming American Heart Association (AHA) 2024 meeting. Both analyses will be published in The New England Journal of Medicine at that time, Jolly reported.

The study involved 104 sites in Australia, Egypt, Europe, Nepal, and North America. Follow-up in both groups exceeded 99%. Most patients had an ST-elevation MI (STEMI), but about 5% of those enrolled had a non-STEMI. Less than 10% of patients had experienced a previous MI.

Less than 5% of patients were discharged on sodium-glucose cotransporter 2 therapy, and more than 95% were discharged on aspirin and a statin. Nearly 80% were discharged on an angiotensin-converting enzyme inhibitor, and most patients received an anticoagulant. More than 95% of patients were implanted with a drug-eluting stent.

At month 3, C-reactive protein levels were significantly lower in the colchicine group than in the placebo group. C-reactive protein is a biomarker for the anti-inflammatory effect that is considered to be colchicine’s primary mechanism of action. An anti-inflammatory effect has been cited as the probable explanation for the positive results shown in the COLCOT and LODOCO2 trials, published in 2019 and 2020, respectively.

In COLCOT, which randomized 4745 patients who experienced an acute MI in the previous 30 days, colchicine was associated with a 23% reduction in a composite major cardiovascular adverse events endpoint relative to placebo (HR, 0.77; P = .02). In LODOCO2, which randomized 5522 patients with chronic coronary disease, colchicine was associated with a 31% reduction in an adverse event composite endpoint (HR, 0.68; P < .0001).

However, two more recent trials — CONVINCE and CHANCE-3 — showed no difference between colchicine and placebo for the endpoint of recurrent stroke at 90 days. CONVINCE, with approximately 3000 patients, was relatively small, whereas CHANCE-3 randomized more than 8000 patients and showed no effect on the risk for stroke (HR, 0.98; 95% CI, 0.83-1.16).

 

New Data Challenge Guidelines

Of these trials, COLCOT was the most similar to OASIS 9, according to Jolly. Among the differences, OASIS 9 was initiated earlier and was larger than the other trials, so it had more power to address the study question.

Given the absence of benefit, Jolly indicated that OASIS 9 might disrupt both the joint American College of Cardiology and AHA guidelines, which gave colchicine a class 2b recommendation in 2023, and the European Society of Cardiology guidelines, which gave colchicine a 2a recommendation.

“This is a big deal for me,” said Ajay J. Kirtane, director of the Interventional Cardiovascular Care program at Columbia University in New York City. As someone who is now using colchicine routinely, these data have changed his opinion.

The previous data supporting the use of colchicine “were just so-so,” he explained. “Now I have a good rationale” for foregoing the routine use of this therapy.

Jolly said that he had put his own father on colchicine after an acute MI on the basis of the guidelines, but immediately took him off this therapy when the data from OASIS 9 were unblinded.

“The only signal from this trial was an increased risk of diarrhea,” Jolly said. The results, at the very least, suggest that colchicine “is not for everyone” after an acute MI, although he emphasized that these results do not rule out the potential for benefit from anti-inflammatory therapy. Ongoing trials, including one targeting interleukin 6, a cytokine associated with inflammation, remain of interest, he added.

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

WASHINGTON — Colchicine does not protect against major cardiovascular adverse events after an acute myocardial infarction, according to a multinational placebo-controlled trial of more than 7000 patients.

The CLEAR SYNERGY (OASIS 9) study, called “the largest trial ever of colchicine in acute MI,” showed no hint of benefit in an adverse event curve for colchicine relative to placebo over 5 years, which suggests that the role of this drug after myocardial infarction (MI) “is uncertain,” Sanjit Jolly, MD, an interventional cardiologist at Hamilton Health Sciences and a professor of medicine at McMaster University in Hamilton, Ontario, Canada, reported at Transcatheter Cardiovascular Therapeutics (TCT) 2024.

For the primary composite outcome — cardiovascular death, MI, stroke, and ischemia-driven revascularization — the event curves in the colchicine and placebo groups remained essentially superimposed over 5 years of follow-up, with only a slight separation after 4 years. The hazard ratio for the primary endpoint showed a 1% difference in favor of colchicine (hazard ratio [HR], 0.99; P = .93).

There were no meaningful differences in any of the individual endpoint components; all 95% CIs straddled the line of unity. Rates of cardiovascular death (3.3% vs 3.2%) and stroke (1.4% vs 1.2%) were numerically higher in the colchicine group than in the placebo group. Rates of MI (2.9% vs 3.1%) and ischemia-driven revascularization (4.6% vs 4.7%) were numerically lower in the colchicine group.

 

No Difference

No adverse outcomes, including all-cause death (4.6% vs 5.1%), approached significance, with the exception of noncardiovascular death (13.0% vs 1.9%). For this outcome, the 95% CI stopped just short of the line of unity (HR, 0.68; 95% CI, 0.46-0.99).

Rates of adverse events (31.9% vs 31.7%; P = .86), serious adverse events (6.7% vs 7.4%; P = .22), and serious infections (2.5% vs 2.9%; P = .85) were similar in the colchicine and placebo groups, but diarrhea, a known side effect of colchicine, was higher in the colchicine group (10.2% vs 6.6%; P < .001).

Given these results, a panelist questioned the use of the word “uncertain” to describe the findings during the late-breaker session in which these results were presented.

“I think you are selling yourself short,” said J. Dawn Abbott, MD, director of the Interventional Cardiology Fellowship Training Program at the Lifespan Cardiovascular Institute, Brown University in Providence, Rhode Island. Based on the size and conduct of this trial, she called the results “definitive” and suggested that the guidelines should be adjusted.

 

The OASIS 9 Trial

In OASIS 9, 3528 patients were randomized to colchicine, and 3534 were randomized to placebo. A second randomization in both groups was to spironolactone or placebo; these results will be presented at the upcoming American Heart Association (AHA) 2024 meeting. Both analyses will be published in The New England Journal of Medicine at that time, Jolly reported.

The study involved 104 sites in Australia, Egypt, Europe, Nepal, and North America. Follow-up in both groups exceeded 99%. Most patients had an ST-elevation MI (STEMI), but about 5% of those enrolled had a non-STEMI. Less than 10% of patients had experienced a previous MI.

Less than 5% of patients were discharged on sodium-glucose cotransporter 2 therapy, and more than 95% were discharged on aspirin and a statin. Nearly 80% were discharged on an angiotensin-converting enzyme inhibitor, and most patients received an anticoagulant. More than 95% of patients were implanted with a drug-eluting stent.

At month 3, C-reactive protein levels were significantly lower in the colchicine group than in the placebo group. C-reactive protein is a biomarker for the anti-inflammatory effect that is considered to be colchicine’s primary mechanism of action. An anti-inflammatory effect has been cited as the probable explanation for the positive results shown in the COLCOT and LODOCO2 trials, published in 2019 and 2020, respectively.

In COLCOT, which randomized 4745 patients who experienced an acute MI in the previous 30 days, colchicine was associated with a 23% reduction in a composite major cardiovascular adverse events endpoint relative to placebo (HR, 0.77; P = .02). In LODOCO2, which randomized 5522 patients with chronic coronary disease, colchicine was associated with a 31% reduction in an adverse event composite endpoint (HR, 0.68; P < .0001).

However, two more recent trials — CONVINCE and CHANCE-3 — showed no difference between colchicine and placebo for the endpoint of recurrent stroke at 90 days. CONVINCE, with approximately 3000 patients, was relatively small, whereas CHANCE-3 randomized more than 8000 patients and showed no effect on the risk for stroke (HR, 0.98; 95% CI, 0.83-1.16).

 

New Data Challenge Guidelines

Of these trials, COLCOT was the most similar to OASIS 9, according to Jolly. Among the differences, OASIS 9 was initiated earlier and was larger than the other trials, so it had more power to address the study question.

Given the absence of benefit, Jolly indicated that OASIS 9 might disrupt both the joint American College of Cardiology and AHA guidelines, which gave colchicine a class 2b recommendation in 2023, and the European Society of Cardiology guidelines, which gave colchicine a 2a recommendation.

“This is a big deal for me,” said Ajay J. Kirtane, director of the Interventional Cardiovascular Care program at Columbia University in New York City. As someone who is now using colchicine routinely, these data have changed his opinion.

The previous data supporting the use of colchicine “were just so-so,” he explained. “Now I have a good rationale” for foregoing the routine use of this therapy.

Jolly said that he had put his own father on colchicine after an acute MI on the basis of the guidelines, but immediately took him off this therapy when the data from OASIS 9 were unblinded.

“The only signal from this trial was an increased risk of diarrhea,” Jolly said. The results, at the very least, suggest that colchicine “is not for everyone” after an acute MI, although he emphasized that these results do not rule out the potential for benefit from anti-inflammatory therapy. Ongoing trials, including one targeting interleukin 6, a cytokine associated with inflammation, remain of interest, he added.

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

WASHINGTON — Colchicine does not protect against major cardiovascular adverse events after an acute myocardial infarction, according to a multinational placebo-controlled trial of more than 7000 patients.

The CLEAR SYNERGY (OASIS 9) study, called “the largest trial ever of colchicine in acute MI,” showed no hint of benefit in an adverse event curve for colchicine relative to placebo over 5 years, which suggests that the role of this drug after myocardial infarction (MI) “is uncertain,” Sanjit Jolly, MD, an interventional cardiologist at Hamilton Health Sciences and a professor of medicine at McMaster University in Hamilton, Ontario, Canada, reported at Transcatheter Cardiovascular Therapeutics (TCT) 2024.

For the primary composite outcome — cardiovascular death, MI, stroke, and ischemia-driven revascularization — the event curves in the colchicine and placebo groups remained essentially superimposed over 5 years of follow-up, with only a slight separation after 4 years. The hazard ratio for the primary endpoint showed a 1% difference in favor of colchicine (hazard ratio [HR], 0.99; P = .93).

There were no meaningful differences in any of the individual endpoint components; all 95% CIs straddled the line of unity. Rates of cardiovascular death (3.3% vs 3.2%) and stroke (1.4% vs 1.2%) were numerically higher in the colchicine group than in the placebo group. Rates of MI (2.9% vs 3.1%) and ischemia-driven revascularization (4.6% vs 4.7%) were numerically lower in the colchicine group.

 

No Difference

No adverse outcomes, including all-cause death (4.6% vs 5.1%), approached significance, with the exception of noncardiovascular death (13.0% vs 1.9%). For this outcome, the 95% CI stopped just short of the line of unity (HR, 0.68; 95% CI, 0.46-0.99).

Rates of adverse events (31.9% vs 31.7%; P = .86), serious adverse events (6.7% vs 7.4%; P = .22), and serious infections (2.5% vs 2.9%; P = .85) were similar in the colchicine and placebo groups, but diarrhea, a known side effect of colchicine, was higher in the colchicine group (10.2% vs 6.6%; P < .001).

Given these results, a panelist questioned the use of the word “uncertain” to describe the findings during the late-breaker session in which these results were presented.

“I think you are selling yourself short,” said J. Dawn Abbott, MD, director of the Interventional Cardiology Fellowship Training Program at the Lifespan Cardiovascular Institute, Brown University in Providence, Rhode Island. Based on the size and conduct of this trial, she called the results “definitive” and suggested that the guidelines should be adjusted.

 

The OASIS 9 Trial

In OASIS 9, 3528 patients were randomized to colchicine, and 3534 were randomized to placebo. A second randomization in both groups was to spironolactone or placebo; these results will be presented at the upcoming American Heart Association (AHA) 2024 meeting. Both analyses will be published in The New England Journal of Medicine at that time, Jolly reported.

The study involved 104 sites in Australia, Egypt, Europe, Nepal, and North America. Follow-up in both groups exceeded 99%. Most patients had an ST-elevation MI (STEMI), but about 5% of those enrolled had a non-STEMI. Less than 10% of patients had experienced a previous MI.

Less than 5% of patients were discharged on sodium-glucose cotransporter 2 therapy, and more than 95% were discharged on aspirin and a statin. Nearly 80% were discharged on an angiotensin-converting enzyme inhibitor, and most patients received an anticoagulant. More than 95% of patients were implanted with a drug-eluting stent.

At month 3, C-reactive protein levels were significantly lower in the colchicine group than in the placebo group. C-reactive protein is a biomarker for the anti-inflammatory effect that is considered to be colchicine’s primary mechanism of action. An anti-inflammatory effect has been cited as the probable explanation for the positive results shown in the COLCOT and LODOCO2 trials, published in 2019 and 2020, respectively.

In COLCOT, which randomized 4745 patients who experienced an acute MI in the previous 30 days, colchicine was associated with a 23% reduction in a composite major cardiovascular adverse events endpoint relative to placebo (HR, 0.77; P = .02). In LODOCO2, which randomized 5522 patients with chronic coronary disease, colchicine was associated with a 31% reduction in an adverse event composite endpoint (HR, 0.68; P < .0001).

However, two more recent trials — CONVINCE and CHANCE-3 — showed no difference between colchicine and placebo for the endpoint of recurrent stroke at 90 days. CONVINCE, with approximately 3000 patients, was relatively small, whereas CHANCE-3 randomized more than 8000 patients and showed no effect on the risk for stroke (HR, 0.98; 95% CI, 0.83-1.16).

 

New Data Challenge Guidelines

Of these trials, COLCOT was the most similar to OASIS 9, according to Jolly. Among the differences, OASIS 9 was initiated earlier and was larger than the other trials, so it had more power to address the study question.

Given the absence of benefit, Jolly indicated that OASIS 9 might disrupt both the joint American College of Cardiology and AHA guidelines, which gave colchicine a class 2b recommendation in 2023, and the European Society of Cardiology guidelines, which gave colchicine a 2a recommendation.

“This is a big deal for me,” said Ajay J. Kirtane, director of the Interventional Cardiovascular Care program at Columbia University in New York City. As someone who is now using colchicine routinely, these data have changed his opinion.

The previous data supporting the use of colchicine “were just so-so,” he explained. “Now I have a good rationale” for foregoing the routine use of this therapy.

Jolly said that he had put his own father on colchicine after an acute MI on the basis of the guidelines, but immediately took him off this therapy when the data from OASIS 9 were unblinded.

“The only signal from this trial was an increased risk of diarrhea,” Jolly said. The results, at the very least, suggest that colchicine “is not for everyone” after an acute MI, although he emphasized that these results do not rule out the potential for benefit from anti-inflammatory therapy. Ongoing trials, including one targeting interleukin 6, a cytokine associated with inflammation, remain of interest, he added.

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

TOPLINE:

Antibiotic use during influenza infection increases lung eosinophils, impairing immunity against secondary bacterial pneumonia. This study highlights the detrimental effects of antibiotics on lung health during viral infections.

METHODOLOGY:

• Researchers conducted a murine model study to evaluate the impact of antibiotic use during influenza infection on lung immunity. Mice were treated with a broad-spectrum antibiotic cocktail (vancomycin, neomycin, ampicillin, and metronidazole) starting 7 days before influenza infection.
• The study included intranasal infection with influenza virus followed by a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA).
• Lung eosinophils, macrophage function, and MRSA clearance were assessed through various immunologic and histologic analyses.
• Finally, in sub-study, a total of three cohorts of hospitalized patients were evaluated to correlate eosinophil levels with antibiotic use, systemic inflammation, and outcomes.

TAKEAWAY:

• Antibiotic use during influenza infection impairs lung immunity, leading to increased lung eosinophils and reduced macrophage function.
• The study found that antibiotic treatment during influenza infection caused fungal dysbiosis, driving lung eosinophilia and impairing MRSA clearance.
• The detrimental effects of antibiotics on lung immunity were specific to the two-hit model of influenza followed by MRSA infection in mice.
• In hospitalized patients, eosinophil levels positively correlated with antibiotic use, systemic inflammation, and worsened outcomes.

IN PRACTICE:

“Our study highlights the pernicious effects of antibiotic use during viral infections and defines a mechanism whereby antibiotics perturb the gut mycobiome and result in lung eosinophilia. In turn, lung eosinophils, via release of MBP-1, suppress alveolar macrophage clearance of bacteria,” the authors of the study wrote.

SOURCE:

This study was led by Marilia Sanches Santos Rizzo Zuttion, Cedars-Sinai Medical Center in Los Angeles. It was published online in The Journal of Clinical Investigation.

LIMITATIONS:

This study’s limitations included the use of a murine model, which may not fully replicate human immune responses. Additionally, the study focused on a specific antibiotic cocktail, and results may vary with different antibiotics. The findings were also specific to the two-hit model of influenza followed by MRSA infection, limiting generalizability to other infections.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Marilia Sanches Santos Rizzo Zuttion received research funding from Pfizer Inc. Additional disclosures are noted in the original article.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Antibiotic use during influenza infection increases lung eosinophils, impairing immunity against secondary bacterial pneumonia. This study highlights the detrimental effects of antibiotics on lung health during viral infections.

METHODOLOGY:

• Researchers conducted a murine model study to evaluate the impact of antibiotic use during influenza infection on lung immunity. Mice were treated with a broad-spectrum antibiotic cocktail (vancomycin, neomycin, ampicillin, and metronidazole) starting 7 days before influenza infection.
• The study included intranasal infection with influenza virus followed by a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA).
• Lung eosinophils, macrophage function, and MRSA clearance were assessed through various immunologic and histologic analyses.
• Finally, in sub-study, a total of three cohorts of hospitalized patients were evaluated to correlate eosinophil levels with antibiotic use, systemic inflammation, and outcomes.

TAKEAWAY:

• Antibiotic use during influenza infection impairs lung immunity, leading to increased lung eosinophils and reduced macrophage function.
• The study found that antibiotic treatment during influenza infection caused fungal dysbiosis, driving lung eosinophilia and impairing MRSA clearance.
• The detrimental effects of antibiotics on lung immunity were specific to the two-hit model of influenza followed by MRSA infection in mice.
• In hospitalized patients, eosinophil levels positively correlated with antibiotic use, systemic inflammation, and worsened outcomes.

IN PRACTICE:

“Our study highlights the pernicious effects of antibiotic use during viral infections and defines a mechanism whereby antibiotics perturb the gut mycobiome and result in lung eosinophilia. In turn, lung eosinophils, via release of MBP-1, suppress alveolar macrophage clearance of bacteria,” the authors of the study wrote.

SOURCE:

This study was led by Marilia Sanches Santos Rizzo Zuttion, Cedars-Sinai Medical Center in Los Angeles. It was published online in The Journal of Clinical Investigation.

LIMITATIONS:

This study’s limitations included the use of a murine model, which may not fully replicate human immune responses. Additionally, the study focused on a specific antibiotic cocktail, and results may vary with different antibiotics. The findings were also specific to the two-hit model of influenza followed by MRSA infection, limiting generalizability to other infections.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Marilia Sanches Santos Rizzo Zuttion received research funding from Pfizer Inc. Additional disclosures are noted in the original article.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Antibiotic use during influenza infection increases lung eosinophils, impairing immunity against secondary bacterial pneumonia. This study highlights the detrimental effects of antibiotics on lung health during viral infections.

METHODOLOGY:

• Researchers conducted a murine model study to evaluate the impact of antibiotic use during influenza infection on lung immunity. Mice were treated with a broad-spectrum antibiotic cocktail (vancomycin, neomycin, ampicillin, and metronidazole) starting 7 days before influenza infection.
• The study included intranasal infection with influenza virus followed by a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA).
• Lung eosinophils, macrophage function, and MRSA clearance were assessed through various immunologic and histologic analyses.
• Finally, in sub-study, a total of three cohorts of hospitalized patients were evaluated to correlate eosinophil levels with antibiotic use, systemic inflammation, and outcomes.

TAKEAWAY:

• Antibiotic use during influenza infection impairs lung immunity, leading to increased lung eosinophils and reduced macrophage function.
• The study found that antibiotic treatment during influenza infection caused fungal dysbiosis, driving lung eosinophilia and impairing MRSA clearance.
• The detrimental effects of antibiotics on lung immunity were specific to the two-hit model of influenza followed by MRSA infection in mice.
• In hospitalized patients, eosinophil levels positively correlated with antibiotic use, systemic inflammation, and worsened outcomes.

IN PRACTICE:

“Our study highlights the pernicious effects of antibiotic use during viral infections and defines a mechanism whereby antibiotics perturb the gut mycobiome and result in lung eosinophilia. In turn, lung eosinophils, via release of MBP-1, suppress alveolar macrophage clearance of bacteria,” the authors of the study wrote.

SOURCE:

This study was led by Marilia Sanches Santos Rizzo Zuttion, Cedars-Sinai Medical Center in Los Angeles. It was published online in The Journal of Clinical Investigation.

LIMITATIONS:

This study’s limitations included the use of a murine model, which may not fully replicate human immune responses. Additionally, the study focused on a specific antibiotic cocktail, and results may vary with different antibiotics. The findings were also specific to the two-hit model of influenza followed by MRSA infection, limiting generalizability to other infections.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Marilia Sanches Santos Rizzo Zuttion received research funding from Pfizer Inc. Additional disclosures are noted in the original article.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

PHILADELPHIA — New research provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) do not increase the risk for pancreatic cancer.

Instead, the large electronic health record (EHR) analysis of patients with type 2 diabetes (T2D) found those taking GLP-1 RAs had a significantly lower risk for pancreatic cancer than peers on other antidiabetic medications. 

“Although there were previous reports suggesting possible association between pancreatic cancer and GLP-1 receptor agonist medications, this study provides reassurance that there is no observed increased incidence of pancreatic cancer in patients prescribed these medications,” said Khaled Alsabbagh Alchirazi, MD, a gastroenterology fellow with Aurora Healthcare in Brookfield, Wisconsin. 

He presented the study findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. 

 

Important Topic

Patients with T2D are at increased risk for several malignancies, including pancreatic cancer. Given the unique mechanism of action of GLP-1 RAs in the pancreas, it was important to investigate the relationship between use of these drugs and incidence of pancreatic cancer, he explained.

Using the TriNetX database, the study team identified 4.95 million antidiabetic drug naive T2D patients who were prescribed antidiabetic medications for the first time between 2005 and 2020. None had a history of pancreatic cancer. 

A total of 245,532 were prescribed a GLP-1 RA. The researchers compared GLP-1 RAs users to users of other antidiabetic medications — namely, insulin, metformin, alpha-glucosidase inhibitors, dipeptidyl-peptidase 4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), sulfonylureas, and thiazolidinediones. 

Patients were propensity score-matched based on demographics, health determinants, lifestyle factors, medical history, family history of cancers, and acute/chronic pancreatitis. 

The risk for pancreatic cancer was significantly lower among patients on GLP-1 RAs vs insulin (hazard ratio [HR], 0.47; 95% CI, 0.40-0.55), DPP-4i (HR, 0.80; 95% CI, 0.73-0.89), SGLT2i (HR, 0.78; 95% CI, 0.69-0.89), and sulfonylureas (HR, 0.84; 95% CI, 0.74-0.95), Alchirazi reported.

The results were consistent across different groups, including patients with obesity/ overweight on GLP-1 RAs vs insulin (HR, 0.53; 95% CI, 0.43-0.65) and SGLT2i (HR, 0.81; 95% CI, 0.69-0.96).

Strengths of the analysis included the large and diverse cohort of propensity score-matched patients. Limitations included the retrospective design and use of claims data that did not provide granular data on pathology reports.

The study by Alchirazi and colleagues aligns with a large population-based cohort study from Israel that found no evidence that GLP-1 RAs increase risk for pancreatic cancer over 7 years following initiation.

Separately, a study of more than 1.6 million patients with T2D found that treatment with a GLP-1 RA (vs insulin or metformin) was associated with lower risks for specific types of obesity-related cancers, including pancreatic cancer.

The study had no specific funding. Alchirazi had no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — New research provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) do not increase the risk for pancreatic cancer.

Instead, the large electronic health record (EHR) analysis of patients with type 2 diabetes (T2D) found those taking GLP-1 RAs had a significantly lower risk for pancreatic cancer than peers on other antidiabetic medications. 

“Although there were previous reports suggesting possible association between pancreatic cancer and GLP-1 receptor agonist medications, this study provides reassurance that there is no observed increased incidence of pancreatic cancer in patients prescribed these medications,” said Khaled Alsabbagh Alchirazi, MD, a gastroenterology fellow with Aurora Healthcare in Brookfield, Wisconsin. 

He presented the study findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. 

 

Important Topic

Patients with T2D are at increased risk for several malignancies, including pancreatic cancer. Given the unique mechanism of action of GLP-1 RAs in the pancreas, it was important to investigate the relationship between use of these drugs and incidence of pancreatic cancer, he explained.

Using the TriNetX database, the study team identified 4.95 million antidiabetic drug naive T2D patients who were prescribed antidiabetic medications for the first time between 2005 and 2020. None had a history of pancreatic cancer. 

A total of 245,532 were prescribed a GLP-1 RA. The researchers compared GLP-1 RAs users to users of other antidiabetic medications — namely, insulin, metformin, alpha-glucosidase inhibitors, dipeptidyl-peptidase 4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), sulfonylureas, and thiazolidinediones. 

Patients were propensity score-matched based on demographics, health determinants, lifestyle factors, medical history, family history of cancers, and acute/chronic pancreatitis. 

The risk for pancreatic cancer was significantly lower among patients on GLP-1 RAs vs insulin (hazard ratio [HR], 0.47; 95% CI, 0.40-0.55), DPP-4i (HR, 0.80; 95% CI, 0.73-0.89), SGLT2i (HR, 0.78; 95% CI, 0.69-0.89), and sulfonylureas (HR, 0.84; 95% CI, 0.74-0.95), Alchirazi reported.

The results were consistent across different groups, including patients with obesity/ overweight on GLP-1 RAs vs insulin (HR, 0.53; 95% CI, 0.43-0.65) and SGLT2i (HR, 0.81; 95% CI, 0.69-0.96).

Strengths of the analysis included the large and diverse cohort of propensity score-matched patients. Limitations included the retrospective design and use of claims data that did not provide granular data on pathology reports.

The study by Alchirazi and colleagues aligns with a large population-based cohort study from Israel that found no evidence that GLP-1 RAs increase risk for pancreatic cancer over 7 years following initiation.

Separately, a study of more than 1.6 million patients with T2D found that treatment with a GLP-1 RA (vs insulin or metformin) was associated with lower risks for specific types of obesity-related cancers, including pancreatic cancer.

The study had no specific funding. Alchirazi had no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — New research provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) do not increase the risk for pancreatic cancer.

Instead, the large electronic health record (EHR) analysis of patients with type 2 diabetes (T2D) found those taking GLP-1 RAs had a significantly lower risk for pancreatic cancer than peers on other antidiabetic medications. 

“Although there were previous reports suggesting possible association between pancreatic cancer and GLP-1 receptor agonist medications, this study provides reassurance that there is no observed increased incidence of pancreatic cancer in patients prescribed these medications,” said Khaled Alsabbagh Alchirazi, MD, a gastroenterology fellow with Aurora Healthcare in Brookfield, Wisconsin. 

He presented the study findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. 

 

Important Topic

Patients with T2D are at increased risk for several malignancies, including pancreatic cancer. Given the unique mechanism of action of GLP-1 RAs in the pancreas, it was important to investigate the relationship between use of these drugs and incidence of pancreatic cancer, he explained.

Using the TriNetX database, the study team identified 4.95 million antidiabetic drug naive T2D patients who were prescribed antidiabetic medications for the first time between 2005 and 2020. None had a history of pancreatic cancer. 

A total of 245,532 were prescribed a GLP-1 RA. The researchers compared GLP-1 RAs users to users of other antidiabetic medications — namely, insulin, metformin, alpha-glucosidase inhibitors, dipeptidyl-peptidase 4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), sulfonylureas, and thiazolidinediones. 

Patients were propensity score-matched based on demographics, health determinants, lifestyle factors, medical history, family history of cancers, and acute/chronic pancreatitis. 

The risk for pancreatic cancer was significantly lower among patients on GLP-1 RAs vs insulin (hazard ratio [HR], 0.47; 95% CI, 0.40-0.55), DPP-4i (HR, 0.80; 95% CI, 0.73-0.89), SGLT2i (HR, 0.78; 95% CI, 0.69-0.89), and sulfonylureas (HR, 0.84; 95% CI, 0.74-0.95), Alchirazi reported.

The results were consistent across different groups, including patients with obesity/ overweight on GLP-1 RAs vs insulin (HR, 0.53; 95% CI, 0.43-0.65) and SGLT2i (HR, 0.81; 95% CI, 0.69-0.96).

Strengths of the analysis included the large and diverse cohort of propensity score-matched patients. Limitations included the retrospective design and use of claims data that did not provide granular data on pathology reports.

The study by Alchirazi and colleagues aligns with a large population-based cohort study from Israel that found no evidence that GLP-1 RAs increase risk for pancreatic cancer over 7 years following initiation.

Separately, a study of more than 1.6 million patients with T2D found that treatment with a GLP-1 RA (vs insulin or metformin) was associated with lower risks for specific types of obesity-related cancers, including pancreatic cancer.

The study had no specific funding. Alchirazi had no relevant disclosures.

A version of this article appeared on Medscape.com.

LAS VEGAS — No matter which treatment regimen is recommended for patients with acne, it should always include a topical retinoid, according to dermatologist Hilary Baldwin, MD.

Patients with successfully treated acne typically use an average of 2.53 different medications, Baldwin, director of the Acne Treatment & Research Center, Brooklyn, New York, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference.

 

“Combination treatment is the name of the game, but how do we convince our patients that what we chose is carefully orchestrated?” she said. “Combination therapy is much more effective, yet we’re always told, ‘keep it simple.’ The trick is to use combination products that have two or three medications in them — fixed combinations and products with excellent vehicles.”

No matter what treatment regimen is recommended for patients with acne, she continued, it should always include a topical retinoid. Tretinoin was the first topical retinoid approved for acne treatment in 1971, followed by adapalene in 1996, tazarotene in 1997, and trifarotene in 2019. According to a review article , topical retinoids inhibit the formation of microcomedones, reduce mature comedones and inflammatory lesions, enhance penetration of other drugs, reduce and prevent scarring, reduce hyperpigmentation, and maintain remission of acne.

More recently, authors of the 2024 American Academy of Dermatology guidelines of care for the management of acne vulgaris strongly recommended the use of topical retinoids based on moderate certainty evidence in the medial literature. Strong recommendations are also made for benzoyl peroxide, topical antibiotics, and oral doxycycline.

Baldwin noted that the benefits of retinoids include their comedolytic and anti-comedogenic properties, their effectiveness in treating inflammatory lesions, and their suitability for long-term maintenance. However, their drawbacks involve the potential for irritancy, which can be concentration- and vehicle-dependent.

Irritancy “maxes out at 1-2 weeks, but the problem is you lose the patient at 2 weeks unless they know it’s coming,” she said, noting that she once heard the 2-week mark characterized as a “crisis of confidence.” Patients “came in with a bunch of pimples, and now they’re red and flaky and burning and stinging [from the retinoid], yet they still have pimples,” Baldwin said. “You really need to talk them through that 2-week mark [or] they’re going to stop the medication.”

To improve retinoid tolerability, Baldwin offered the following tips:

• Use a pea-sized amount for the entire affected area and avoid spot treatments.
• Start with every other day application.
• Moisturize regularly, possibly applying moisturizer before the retinoid.
• Consider switching to a different formulation with an alternative vehicle or retinoid delivery system. Adapalene and tazarotene are the only retinoids that have proven to be stable in the presence of benzoyl peroxide, she said.
• Be persistent. “There is no such thing as a patient who cannot tolerate a retinoid,” said Baldwin, the lead author of a review on the evolution of topical retinoids for acne. “It’s because of a provider who failed to provide a sufficient amount of information to allow the patient to eventually be able to tolerate a retinoid.”

Baldwin also referred to an independent meta-analysis of 221 trials comparing the efficacy of pharmacological therapies for acne in patients of any age, which found that the percentage reduction in total lesion count, compared with placebo, was the highest with oral isotretinoin (mean difference [MD], 48.41; P = 1.00), followed by triple therapy containing a topical antibiotic, a topical retinoid, and benzoyl peroxide (MD, 38.15; P = .95), and by triple therapy containing an oral antibiotic, a topical retinoid, and benzoyl peroxide (MD, 34.83; P = .90).

Baldwin is a former president of the American Acne & Rosacea Society and is the SDPA conference medical director. She disclosed being a speaker, consultant, and/or an advisory board member for Almirall, Arcutis, Bausch, Beiersdorf, Cutera, Galderma, Journey, Kenvue, La Roche-Posay, L’Oreal, Sanofi, Sun Pharma, and Tarsus Pharmaceuticals.

 

A version of this article appeared on Medscape.com.

LAS VEGAS — No matter which treatment regimen is recommended for patients with acne, it should always include a topical retinoid, according to dermatologist Hilary Baldwin, MD.

Patients with successfully treated acne typically use an average of 2.53 different medications, Baldwin, director of the Acne Treatment & Research Center, Brooklyn, New York, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference.

 

“Combination treatment is the name of the game, but how do we convince our patients that what we chose is carefully orchestrated?” she said. “Combination therapy is much more effective, yet we’re always told, ‘keep it simple.’ The trick is to use combination products that have two or three medications in them — fixed combinations and products with excellent vehicles.”

No matter what treatment regimen is recommended for patients with acne, she continued, it should always include a topical retinoid. Tretinoin was the first topical retinoid approved for acne treatment in 1971, followed by adapalene in 1996, tazarotene in 1997, and trifarotene in 2019. According to a review article , topical retinoids inhibit the formation of microcomedones, reduce mature comedones and inflammatory lesions, enhance penetration of other drugs, reduce and prevent scarring, reduce hyperpigmentation, and maintain remission of acne.

More recently, authors of the 2024 American Academy of Dermatology guidelines of care for the management of acne vulgaris strongly recommended the use of topical retinoids based on moderate certainty evidence in the medial literature. Strong recommendations are also made for benzoyl peroxide, topical antibiotics, and oral doxycycline.

Baldwin noted that the benefits of retinoids include their comedolytic and anti-comedogenic properties, their effectiveness in treating inflammatory lesions, and their suitability for long-term maintenance. However, their drawbacks involve the potential for irritancy, which can be concentration- and vehicle-dependent.

Irritancy “maxes out at 1-2 weeks, but the problem is you lose the patient at 2 weeks unless they know it’s coming,” she said, noting that she once heard the 2-week mark characterized as a “crisis of confidence.” Patients “came in with a bunch of pimples, and now they’re red and flaky and burning and stinging [from the retinoid], yet they still have pimples,” Baldwin said. “You really need to talk them through that 2-week mark [or] they’re going to stop the medication.”

To improve retinoid tolerability, Baldwin offered the following tips:

• Use a pea-sized amount for the entire affected area and avoid spot treatments.
• Start with every other day application.
• Moisturize regularly, possibly applying moisturizer before the retinoid.
• Consider switching to a different formulation with an alternative vehicle or retinoid delivery system. Adapalene and tazarotene are the only retinoids that have proven to be stable in the presence of benzoyl peroxide, she said.
• Be persistent. “There is no such thing as a patient who cannot tolerate a retinoid,” said Baldwin, the lead author of a review on the evolution of topical retinoids for acne. “It’s because of a provider who failed to provide a sufficient amount of information to allow the patient to eventually be able to tolerate a retinoid.”

Baldwin also referred to an independent meta-analysis of 221 trials comparing the efficacy of pharmacological therapies for acne in patients of any age, which found that the percentage reduction in total lesion count, compared with placebo, was the highest with oral isotretinoin (mean difference [MD], 48.41; P = 1.00), followed by triple therapy containing a topical antibiotic, a topical retinoid, and benzoyl peroxide (MD, 38.15; P = .95), and by triple therapy containing an oral antibiotic, a topical retinoid, and benzoyl peroxide (MD, 34.83; P = .90).

Baldwin is a former president of the American Acne & Rosacea Society and is the SDPA conference medical director. She disclosed being a speaker, consultant, and/or an advisory board member for Almirall, Arcutis, Bausch, Beiersdorf, Cutera, Galderma, Journey, Kenvue, La Roche-Posay, L’Oreal, Sanofi, Sun Pharma, and Tarsus Pharmaceuticals.

 

A version of this article appeared on Medscape.com.

LAS VEGAS — No matter which treatment regimen is recommended for patients with acne, it should always include a topical retinoid, according to dermatologist Hilary Baldwin, MD.

Patients with successfully treated acne typically use an average of 2.53 different medications, Baldwin, director of the Acne Treatment & Research Center, Brooklyn, New York, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference.

 

“Combination treatment is the name of the game, but how do we convince our patients that what we chose is carefully orchestrated?” she said. “Combination therapy is much more effective, yet we’re always told, ‘keep it simple.’ The trick is to use combination products that have two or three medications in them — fixed combinations and products with excellent vehicles.”

No matter what treatment regimen is recommended for patients with acne, she continued, it should always include a topical retinoid. Tretinoin was the first topical retinoid approved for acne treatment in 1971, followed by adapalene in 1996, tazarotene in 1997, and trifarotene in 2019. According to a review article , topical retinoids inhibit the formation of microcomedones, reduce mature comedones and inflammatory lesions, enhance penetration of other drugs, reduce and prevent scarring, reduce hyperpigmentation, and maintain remission of acne.

More recently, authors of the 2024 American Academy of Dermatology guidelines of care for the management of acne vulgaris strongly recommended the use of topical retinoids based on moderate certainty evidence in the medial literature. Strong recommendations are also made for benzoyl peroxide, topical antibiotics, and oral doxycycline.

Baldwin noted that the benefits of retinoids include their comedolytic and anti-comedogenic properties, their effectiveness in treating inflammatory lesions, and their suitability for long-term maintenance. However, their drawbacks involve the potential for irritancy, which can be concentration- and vehicle-dependent.

Irritancy “maxes out at 1-2 weeks, but the problem is you lose the patient at 2 weeks unless they know it’s coming,” she said, noting that she once heard the 2-week mark characterized as a “crisis of confidence.” Patients “came in with a bunch of pimples, and now they’re red and flaky and burning and stinging [from the retinoid], yet they still have pimples,” Baldwin said. “You really need to talk them through that 2-week mark [or] they’re going to stop the medication.”

To improve retinoid tolerability, Baldwin offered the following tips:

• Use a pea-sized amount for the entire affected area and avoid spot treatments.
• Start with every other day application.
• Moisturize regularly, possibly applying moisturizer before the retinoid.
• Consider switching to a different formulation with an alternative vehicle or retinoid delivery system. Adapalene and tazarotene are the only retinoids that have proven to be stable in the presence of benzoyl peroxide, she said.
• Be persistent. “There is no such thing as a patient who cannot tolerate a retinoid,” said Baldwin, the lead author of a review on the evolution of topical retinoids for acne. “It’s because of a provider who failed to provide a sufficient amount of information to allow the patient to eventually be able to tolerate a retinoid.”

Baldwin also referred to an independent meta-analysis of 221 trials comparing the efficacy of pharmacological therapies for acne in patients of any age, which found that the percentage reduction in total lesion count, compared with placebo, was the highest with oral isotretinoin (mean difference [MD], 48.41; P = 1.00), followed by triple therapy containing a topical antibiotic, a topical retinoid, and benzoyl peroxide (MD, 38.15; P = .95), and by triple therapy containing an oral antibiotic, a topical retinoid, and benzoyl peroxide (MD, 34.83; P = .90).

Baldwin is a former president of the American Acne & Rosacea Society and is the SDPA conference medical director. She disclosed being a speaker, consultant, and/or an advisory board member for Almirall, Arcutis, Bausch, Beiersdorf, Cutera, Galderma, Journey, Kenvue, La Roche-Posay, L’Oreal, Sanofi, Sun Pharma, and Tarsus Pharmaceuticals.

 

A version of this article appeared on Medscape.com.

Signs of frailty may signal future dementia more than a decade before cognitive symptoms occur, in new findings that may provide a potential opportunity to identify high-risk populations for targeted enrollment in clinical trials of dementia prevention and treatment.

Results of an international study assessing frailty trajectories showed frailty levels notably increased in the 4-9 years before dementia diagnosis. Even among study participants whose baseline frailty measurement was taken prior to that acceleration period, frailty was still positively associated with dementia risk, the investigators noted.

“We found that with every four to five additional health problems, there is on average a 40% higher risk of developing dementia, while the risk is lower for people who are more physically fit,” said study investigator David Ward, PhD, of the Centre for Health Services Research, The University of Queensland, Brisbane, Australia.

The findings were published online in JAMA Neurology.

 

A Promising Biomarker

An accessible biomarker for both biologic age and dementia risk is essential for advancing dementia prevention and treatment strategies, the investigators noted, adding that growing evidence suggests frailty may be a promising candidate for this role.

To learn more about the association between frailty and dementia, Ward and his team analyzed data on 29,849 participants aged 60 years or above (mean age, 71.6 years; 62% women) who participated in four cohort studies: the English Longitudinal Study of Ageing (ELSA; n = 6771), the Health and Retirement Study (HRS; n = 9045), the Rush Memory and Aging Project (MAP; n = 1451), and the National Alzheimer’s Coordinating Center (NACC; n = 12,582).

The primary outcome was all-cause dementia. Depending on the cohort, dementia diagnoses were determined through cognitive testing, self- or family report of physician diagnosis, or a diagnosis by the study physician. Participants were excluded if they had cognitive impairment at baseline.

Investigators retrospectively determined frailty index scores by gathering information on health and functional outcomes for participants from each cohort. Only participants with frailty data on at least 30 deficits were included.

Commonly included deficits included high blood pressure, cancer, and chronic pain, as well as functional problems such as hearing impairment, difficulty with mobility, and challenges managing finances.

Investigators conducted follow-up visits with participants until they developed dementia or until the study ended, with follow-up periods varying across cohorts.

After adjustment for potential confounders, frailty scores were modeled using backward time scales.

Among participants who developed incident dementia (n = 3154), covariate-adjusted expected frailty index scores were, on average, higher in women than in men by 18.5% in ELSA, 20.9% in HRS, and 16.2% in MAP. There were no differences in frailty scores between sexes in the NACC cohort.

When measured on a timeline, as compared with those who didn’t develop dementia, frailty scores were significantly and consistently higher in the dementia groups 8-20 before dementia onset (20 years in HRS; 13 in MAP; 12 in ELSA; 8 in NACC).

Increases in the rates of frailty index scores began accelerating 4-9 years before dementia onset for the various cohorts, investigators noted.

In all four cohorts, each 0.1 increase in frailty scores was positively associated with increased dementia risk.

Adjusted hazard ratios [aHRs] ranged from 1.18 in the HRS cohort to 1.73 in the NACC cohort, which showed the strongest association.

In participants whose baseline frailty measurement was conducted before the predementia acceleration period began, the association of frailty scores and dementia risk was positive. These aHRs ranged from 1.18 in the HRS cohort to 1.43 in the NACC cohort.

 

The ‘Four Pillars’ of Prevention

The good news, investigators said, is that the long trajectory of frailty symptoms preceding dementia onset provides plenty of opportunity for intervention.

To slow the development of frailty, Ward suggested adhering to the “four pillars of frailty prevention and management,” which include good nutrition with plenty of protein, exercise, optimizing medications for chronic conditions, and maintaining a strong social network.

Ward suggested neurologists track frailty in their patients and pointed to a recent article focused on helping neurologists use frailty measures to influence care planning.

Study limitations include the possibility of reverse causality and the fact that investigators could not adjust for genetic risk for dementia.

 

Unclear Pathway

Commenting on the findings, Lycia Neumann, PhD, senior director of Health Services Research at the Alzheimer’s Association, noted that many studies over the years have shown a link between frailty and dementia. However, she cautioned that a link does not imply causation.

The pathway from frailty to dementia is not 100% clear, and both are complex conditions, said Neumann, who was not part of the study.

“Adopting healthy lifestyle behaviors early and consistently can help decrease the risk of — or postpone the onset of — both frailty and cognitive decline,” she said. Neumann added that physical activity, a healthy diet, social engagement, and controlling diabetes and blood pressure can also reduce the risk for dementia as well as cardiovascular disease.

The study was funded in part by the Deep Dementia Phenotyping Network through the Frailty and Dementia Special Interest Group. Ward and Neumann reported no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

Signs of frailty may signal future dementia more than a decade before cognitive symptoms occur, in new findings that may provide a potential opportunity to identify high-risk populations for targeted enrollment in clinical trials of dementia prevention and treatment.

Results of an international study assessing frailty trajectories showed frailty levels notably increased in the 4-9 years before dementia diagnosis. Even among study participants whose baseline frailty measurement was taken prior to that acceleration period, frailty was still positively associated with dementia risk, the investigators noted.

“We found that with every four to five additional health problems, there is on average a 40% higher risk of developing dementia, while the risk is lower for people who are more physically fit,” said study investigator David Ward, PhD, of the Centre for Health Services Research, The University of Queensland, Brisbane, Australia.

The findings were published online in JAMA Neurology.

 

A Promising Biomarker

An accessible biomarker for both biologic age and dementia risk is essential for advancing dementia prevention and treatment strategies, the investigators noted, adding that growing evidence suggests frailty may be a promising candidate for this role.

To learn more about the association between frailty and dementia, Ward and his team analyzed data on 29,849 participants aged 60 years or above (mean age, 71.6 years; 62% women) who participated in four cohort studies: the English Longitudinal Study of Ageing (ELSA; n = 6771), the Health and Retirement Study (HRS; n = 9045), the Rush Memory and Aging Project (MAP; n = 1451), and the National Alzheimer’s Coordinating Center (NACC; n = 12,582).

The primary outcome was all-cause dementia. Depending on the cohort, dementia diagnoses were determined through cognitive testing, self- or family report of physician diagnosis, or a diagnosis by the study physician. Participants were excluded if they had cognitive impairment at baseline.

Investigators retrospectively determined frailty index scores by gathering information on health and functional outcomes for participants from each cohort. Only participants with frailty data on at least 30 deficits were included.

Commonly included deficits included high blood pressure, cancer, and chronic pain, as well as functional problems such as hearing impairment, difficulty with mobility, and challenges managing finances.

Investigators conducted follow-up visits with participants until they developed dementia or until the study ended, with follow-up periods varying across cohorts.

After adjustment for potential confounders, frailty scores were modeled using backward time scales.

Among participants who developed incident dementia (n = 3154), covariate-adjusted expected frailty index scores were, on average, higher in women than in men by 18.5% in ELSA, 20.9% in HRS, and 16.2% in MAP. There were no differences in frailty scores between sexes in the NACC cohort.

When measured on a timeline, as compared with those who didn’t develop dementia, frailty scores were significantly and consistently higher in the dementia groups 8-20 before dementia onset (20 years in HRS; 13 in MAP; 12 in ELSA; 8 in NACC).

Increases in the rates of frailty index scores began accelerating 4-9 years before dementia onset for the various cohorts, investigators noted.

In all four cohorts, each 0.1 increase in frailty scores was positively associated with increased dementia risk.

Adjusted hazard ratios [aHRs] ranged from 1.18 in the HRS cohort to 1.73 in the NACC cohort, which showed the strongest association.

In participants whose baseline frailty measurement was conducted before the predementia acceleration period began, the association of frailty scores and dementia risk was positive. These aHRs ranged from 1.18 in the HRS cohort to 1.43 in the NACC cohort.

 

The ‘Four Pillars’ of Prevention

The good news, investigators said, is that the long trajectory of frailty symptoms preceding dementia onset provides plenty of opportunity for intervention.

To slow the development of frailty, Ward suggested adhering to the “four pillars of frailty prevention and management,” which include good nutrition with plenty of protein, exercise, optimizing medications for chronic conditions, and maintaining a strong social network.

Ward suggested neurologists track frailty in their patients and pointed to a recent article focused on helping neurologists use frailty measures to influence care planning.

Study limitations include the possibility of reverse causality and the fact that investigators could not adjust for genetic risk for dementia.

 

Unclear Pathway

Commenting on the findings, Lycia Neumann, PhD, senior director of Health Services Research at the Alzheimer’s Association, noted that many studies over the years have shown a link between frailty and dementia. However, she cautioned that a link does not imply causation.

The pathway from frailty to dementia is not 100% clear, and both are complex conditions, said Neumann, who was not part of the study.

“Adopting healthy lifestyle behaviors early and consistently can help decrease the risk of — or postpone the onset of — both frailty and cognitive decline,” she said. Neumann added that physical activity, a healthy diet, social engagement, and controlling diabetes and blood pressure can also reduce the risk for dementia as well as cardiovascular disease.

The study was funded in part by the Deep Dementia Phenotyping Network through the Frailty and Dementia Special Interest Group. Ward and Neumann reported no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

Signs of frailty may signal future dementia more than a decade before cognitive symptoms occur, in new findings that may provide a potential opportunity to identify high-risk populations for targeted enrollment in clinical trials of dementia prevention and treatment.

Results of an international study assessing frailty trajectories showed frailty levels notably increased in the 4-9 years before dementia diagnosis. Even among study participants whose baseline frailty measurement was taken prior to that acceleration period, frailty was still positively associated with dementia risk, the investigators noted.

“We found that with every four to five additional health problems, there is on average a 40% higher risk of developing dementia, while the risk is lower for people who are more physically fit,” said study investigator David Ward, PhD, of the Centre for Health Services Research, The University of Queensland, Brisbane, Australia.

The findings were published online in JAMA Neurology.

 

A Promising Biomarker

An accessible biomarker for both biologic age and dementia risk is essential for advancing dementia prevention and treatment strategies, the investigators noted, adding that growing evidence suggests frailty may be a promising candidate for this role.

To learn more about the association between frailty and dementia, Ward and his team analyzed data on 29,849 participants aged 60 years or above (mean age, 71.6 years; 62% women) who participated in four cohort studies: the English Longitudinal Study of Ageing (ELSA; n = 6771), the Health and Retirement Study (HRS; n = 9045), the Rush Memory and Aging Project (MAP; n = 1451), and the National Alzheimer’s Coordinating Center (NACC; n = 12,582).

The primary outcome was all-cause dementia. Depending on the cohort, dementia diagnoses were determined through cognitive testing, self- or family report of physician diagnosis, or a diagnosis by the study physician. Participants were excluded if they had cognitive impairment at baseline.

Investigators retrospectively determined frailty index scores by gathering information on health and functional outcomes for participants from each cohort. Only participants with frailty data on at least 30 deficits were included.

Commonly included deficits included high blood pressure, cancer, and chronic pain, as well as functional problems such as hearing impairment, difficulty with mobility, and challenges managing finances.

Investigators conducted follow-up visits with participants until they developed dementia or until the study ended, with follow-up periods varying across cohorts.

After adjustment for potential confounders, frailty scores were modeled using backward time scales.

Among participants who developed incident dementia (n = 3154), covariate-adjusted expected frailty index scores were, on average, higher in women than in men by 18.5% in ELSA, 20.9% in HRS, and 16.2% in MAP. There were no differences in frailty scores between sexes in the NACC cohort.

When measured on a timeline, as compared with those who didn’t develop dementia, frailty scores were significantly and consistently higher in the dementia groups 8-20 before dementia onset (20 years in HRS; 13 in MAP; 12 in ELSA; 8 in NACC).

Increases in the rates of frailty index scores began accelerating 4-9 years before dementia onset for the various cohorts, investigators noted.

In all four cohorts, each 0.1 increase in frailty scores was positively associated with increased dementia risk.

Adjusted hazard ratios [aHRs] ranged from 1.18 in the HRS cohort to 1.73 in the NACC cohort, which showed the strongest association.

In participants whose baseline frailty measurement was conducted before the predementia acceleration period began, the association of frailty scores and dementia risk was positive. These aHRs ranged from 1.18 in the HRS cohort to 1.43 in the NACC cohort.

 

The ‘Four Pillars’ of Prevention

The good news, investigators said, is that the long trajectory of frailty symptoms preceding dementia onset provides plenty of opportunity for intervention.

To slow the development of frailty, Ward suggested adhering to the “four pillars of frailty prevention and management,” which include good nutrition with plenty of protein, exercise, optimizing medications for chronic conditions, and maintaining a strong social network.

Ward suggested neurologists track frailty in their patients and pointed to a recent article focused on helping neurologists use frailty measures to influence care planning.

Study limitations include the possibility of reverse causality and the fact that investigators could not adjust for genetic risk for dementia.

 

Unclear Pathway

Commenting on the findings, Lycia Neumann, PhD, senior director of Health Services Research at the Alzheimer’s Association, noted that many studies over the years have shown a link between frailty and dementia. However, she cautioned that a link does not imply causation.

The pathway from frailty to dementia is not 100% clear, and both are complex conditions, said Neumann, who was not part of the study.

“Adopting healthy lifestyle behaviors early and consistently can help decrease the risk of — or postpone the onset of — both frailty and cognitive decline,” she said. Neumann added that physical activity, a healthy diet, social engagement, and controlling diabetes and blood pressure can also reduce the risk for dementia as well as cardiovascular disease.

The study was funded in part by the Deep Dementia Phenotyping Network through the Frailty and Dementia Special Interest Group. Ward and Neumann reported no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

After more than 10 years of serving in a large academic medical center in Chicago, Illinois, that was part of a national health care system, the decision to transition into private practice wasn’t one I made lightly.

Having built a rewarding career and spent over a quarter of my life in an academic medical center and a national health system, the move to starting an independent practice from scratch was both exciting and daunting. The notion of leaving behind the structure, resources, and safety of the large health system was unsettling. However, as the landscape of health care continues to evolve, with worsening large structural problems within the U.S. health care system, I realized that starting an independent gastroenterology practice — focused on trying to fix some of these large-scale problems from the start — would not only align with my professional goals but also provide the personal satisfaction I had failed to find. 

As I reflect on my journey, there are a few key lessons I learned from making this leap — lessons that helped me transition from a highly structured employed physician environment to leading a thriving independent practice focused on redesigning gastroenterology care from scratch.

Lesson 1: Autonomy Opens the Door to Innovation

One of the primary reasons I left the employed physician setting was to gain greater control over my clinical practice and decision-making processes.

In a national health care system, the goal of standardization often dictates not only clinical care, but many “back end” aspects of the entire health care experience. We often see the things that are more visible, such as what supplies/equipment you use, how your patient appointments are scheduled, how many support staff members are assigned to help your practice, what electronic health record system you use, and how shared resources (like GI lab block time or anesthesia teams) are allocated.

However, this also impacts things we don’t usually see, such as what fees are billed for care you are providing (like facility fees), communication systems that your patients need to navigate for help, human resource systems you use, and retirement/health benefits you and your other team members receive. 

Standardization has two adverse consequences: 1) it does not allow for personalization and as a result, 2) it suppresses innovation. Standard protocols can streamline processes, but they sometimes fail to account for the nuanced differences between patients, such as genetic factors, unique medical histories, or responses/failures to prior treatments. This rigidity can stifle innovation, as physicians are often bound by guidelines that may not reflect the latest advancements or allow for creative, individualized approaches to care. In the long term, an overemphasis on standardization risks turning health care into a one-size-fits-all model, undermining the potential for breakthroughs.

The transition was challenging at first, as we needed to engage our entire new practice with a different mindset now that many of us had autonomy for the first time. Instead of everyone just practicing health care the way they had done before, we took a page from Elon Musk and challenged every member of the team to ask three questions about everything they do on a daily basis:

• Is what I am doing helping a patient get healthy? (Question every requirement)
• If not, do I still need to do this? (Delete any part of the process you can)
• If so, how can I make this easier, faster, or automated? (Simplify and optimize, accelerate cycle time, and automate)

The freedom to innovate is a hallmark of independent practice. Embracing innovation in every aspect of the practice has been the most critical lesson of this journey. 

 

Lesson 2: Financial Stewardship is Critical for Sustainability

Running an independent practice is not just about medicine — it’s also about managing a business.

This was a stark shift from the large academic health systems, where financial decisions were handled by the “administration.” In my new role as a business owner, understanding the financial aspects of health care was crucial for success. The cost of what patients pay for health care in the United States (either directly in deductibles and coinsurance or indirectly through insurance premiums) is unsustainably high. However, inflation continues to cause substantial increases in almost all the costs of delivering care: medical supplies, salaries, benefits, IT costs, etc. It was critical to develop a financial plan that accounted for these two macro-economic trends, and ideally helped solve for both. In our case, delivering high quality care with a lower cost to patients and payers. 

We started by reevaluating our relationship with payers. Whereas being part of a large academic health system, we are often taught to look at payers as the adversary; as an independent practice looking to redesign the health care experience, it was critical for us to look to the payers as a partner in this journey. Understanding payer expectations and structuring contracts that aligned with shared goals of reducing total health care costs for patients was one of the foundations of our financial plan. 

Offering office-based endoscopy was one innovation we implemented to significantly impact both patient affordability and practice revenue. By performing procedures like colonoscopies and upper endoscopies in an office setting rather than a hospital or ambulatory surgery center, we eliminated facility fees, which are often a significant part of the total cost of care. This directly lowers out-of-pocket expenses for patients and reduces the overall financial burden on insurance companies. At the same time, it allows the practice to capture more of the revenue from these procedures, without the overhead costs associated with larger facilities. This model creates a win-win situation: patients save money while receiving the same quality of care, and the practice experiences an increase in profitability and autonomy in managing its services.

 

Lesson 3: Collaborative Care and Multidisciplinary Teams Can Exist Anywhere

One aspect I deeply valued in academia was the collaborative environment — having specialists across disciplines work together on challenging cases. In private practice, I was concerned that I would lose this collegial atmosphere. However, I quickly learned that building a robust network of multidisciplinary collaborators was achievable in independent practice, just like it was in a large health system.

In our practice, we established close relationships with primary care physicians, surgeons, advanced practice providers, dietitians, behavioral health specialists, and others. These partnerships were not just referral networks but integrated care teams where communication and shared decision-making were prioritized. By fostering collaboration, we could offer patients comprehensive care that addressed their physical, psychological, and nutritional needs. 

For example, managing patients with chronic conditions like inflammatory bowel disease, cirrhosis, or obesity requires more than just prescribing medications. It involves regular monitoring, dietary adjustments, psychological support, and in some cases, surgical intervention. In an academic setting, coordinating this level of care can be cumbersome due to institutional barriers and siloed departments. In our practice, some of these relationships are achieved through partnerships with other like-minded practices. In other situations, team members of other disciplines are employed directly by our practice. Being in an independent practice allowed us the flexibility to prioritize working with the right team members first, and then structuring the relationship model second. 

 

Lesson 4: Technology Is a Vital Tool in Redesigning Health Care

When I worked in a large academic health system, technology was often seen as an administrative burden rather than a clinical asset. Electronic health records (EHR) and a lot of the other IT systems that health care workers and patients interacted with on a regular basis were viewed as a barrier to care or a cause of time burdens instead of as tools to make health care easier. As we built our new practice from scratch, it was critical that we had an IT infrastructure that aligned with our core goals: simplify and automate the health care experience for everyone.

For our practice, we didn’t try to re-invent the wheel. Instead we copied from other industries who had already figured out a great solution for a problem we had. We wanted our patients to have a great customer service experience when interacting with our practice for scheduling, questions, refills, etc. So we implemented a unified communication system that some Fortune 100 companies, with perennial high scores for customer service, used. We wanted a great human resource system that would streamline the administrative time it would take to handle all HR needs for our practice. So we implemented an HR information system that had the best ratings for automation and integration with other business systems. At every point in the process, we reminded ourselves to focus on simplification and automation for every user of the system. 

 

Conclusion: A Rewarding Transition

The decision to leave academic medicine and start an independent gastroenterology practice wasn’t easy, but it was one of the most rewarding choices I have made. The lessons I’ve learned along the way — embracing autonomy, understanding financial stewardship, fostering collaboration, and leveraging technology — have helped me work toward a better total health care experience for the community.

This journey has also been deeply fulfilling on a personal level. It has allowed me to build stronger relationships with my patients, focus on long-term health outcomes, and create a practice where innovation and quality truly matter. While the challenges of running a private practice are real, the rewards — both for me and my patients — are immeasurable. If I had to do it all over again, I wouldn’t hesitate for a moment. If anything, I should have done it earlier.

Dr. Gupta is Managing Partner at Midwest Digestive Health & Nutrition, in Des Plaines, Illinois. He has reported no conflicts of interest in relation to this article.

After more than 10 years of serving in a large academic medical center in Chicago, Illinois, that was part of a national health care system, the decision to transition into private practice wasn’t one I made lightly.

Having built a rewarding career and spent over a quarter of my life in an academic medical center and a national health system, the move to starting an independent practice from scratch was both exciting and daunting. The notion of leaving behind the structure, resources, and safety of the large health system was unsettling. However, as the landscape of health care continues to evolve, with worsening large structural problems within the U.S. health care system, I realized that starting an independent gastroenterology practice — focused on trying to fix some of these large-scale problems from the start — would not only align with my professional goals but also provide the personal satisfaction I had failed to find. 

As I reflect on my journey, there are a few key lessons I learned from making this leap — lessons that helped me transition from a highly structured employed physician environment to leading a thriving independent practice focused on redesigning gastroenterology care from scratch.

Lesson 1: Autonomy Opens the Door to Innovation

One of the primary reasons I left the employed physician setting was to gain greater control over my clinical practice and decision-making processes.

In a national health care system, the goal of standardization often dictates not only clinical care, but many “back end” aspects of the entire health care experience. We often see the things that are more visible, such as what supplies/equipment you use, how your patient appointments are scheduled, how many support staff members are assigned to help your practice, what electronic health record system you use, and how shared resources (like GI lab block time or anesthesia teams) are allocated.

However, this also impacts things we don’t usually see, such as what fees are billed for care you are providing (like facility fees), communication systems that your patients need to navigate for help, human resource systems you use, and retirement/health benefits you and your other team members receive. 

Standardization has two adverse consequences: 1) it does not allow for personalization and as a result, 2) it suppresses innovation. Standard protocols can streamline processes, but they sometimes fail to account for the nuanced differences between patients, such as genetic factors, unique medical histories, or responses/failures to prior treatments. This rigidity can stifle innovation, as physicians are often bound by guidelines that may not reflect the latest advancements or allow for creative, individualized approaches to care. In the long term, an overemphasis on standardization risks turning health care into a one-size-fits-all model, undermining the potential for breakthroughs.

The transition was challenging at first, as we needed to engage our entire new practice with a different mindset now that many of us had autonomy for the first time. Instead of everyone just practicing health care the way they had done before, we took a page from Elon Musk and challenged every member of the team to ask three questions about everything they do on a daily basis:

• Is what I am doing helping a patient get healthy? (Question every requirement)
• If not, do I still need to do this? (Delete any part of the process you can)
• If so, how can I make this easier, faster, or automated? (Simplify and optimize, accelerate cycle time, and automate)

The freedom to innovate is a hallmark of independent practice. Embracing innovation in every aspect of the practice has been the most critical lesson of this journey. 

 

Lesson 2: Financial Stewardship is Critical for Sustainability

Running an independent practice is not just about medicine — it’s also about managing a business.

This was a stark shift from the large academic health systems, where financial decisions were handled by the “administration.” In my new role as a business owner, understanding the financial aspects of health care was crucial for success. The cost of what patients pay for health care in the United States (either directly in deductibles and coinsurance or indirectly through insurance premiums) is unsustainably high. However, inflation continues to cause substantial increases in almost all the costs of delivering care: medical supplies, salaries, benefits, IT costs, etc. It was critical to develop a financial plan that accounted for these two macro-economic trends, and ideally helped solve for both. In our case, delivering high quality care with a lower cost to patients and payers. 

We started by reevaluating our relationship with payers. Whereas being part of a large academic health system, we are often taught to look at payers as the adversary; as an independent practice looking to redesign the health care experience, it was critical for us to look to the payers as a partner in this journey. Understanding payer expectations and structuring contracts that aligned with shared goals of reducing total health care costs for patients was one of the foundations of our financial plan. 

Offering office-based endoscopy was one innovation we implemented to significantly impact both patient affordability and practice revenue. By performing procedures like colonoscopies and upper endoscopies in an office setting rather than a hospital or ambulatory surgery center, we eliminated facility fees, which are often a significant part of the total cost of care. This directly lowers out-of-pocket expenses for patients and reduces the overall financial burden on insurance companies. At the same time, it allows the practice to capture more of the revenue from these procedures, without the overhead costs associated with larger facilities. This model creates a win-win situation: patients save money while receiving the same quality of care, and the practice experiences an increase in profitability and autonomy in managing its services.

 

Lesson 3: Collaborative Care and Multidisciplinary Teams Can Exist Anywhere

One aspect I deeply valued in academia was the collaborative environment — having specialists across disciplines work together on challenging cases. In private practice, I was concerned that I would lose this collegial atmosphere. However, I quickly learned that building a robust network of multidisciplinary collaborators was achievable in independent practice, just like it was in a large health system.

In our practice, we established close relationships with primary care physicians, surgeons, advanced practice providers, dietitians, behavioral health specialists, and others. These partnerships were not just referral networks but integrated care teams where communication and shared decision-making were prioritized. By fostering collaboration, we could offer patients comprehensive care that addressed their physical, psychological, and nutritional needs. 

For example, managing patients with chronic conditions like inflammatory bowel disease, cirrhosis, or obesity requires more than just prescribing medications. It involves regular monitoring, dietary adjustments, psychological support, and in some cases, surgical intervention. In an academic setting, coordinating this level of care can be cumbersome due to institutional barriers and siloed departments. In our practice, some of these relationships are achieved through partnerships with other like-minded practices. In other situations, team members of other disciplines are employed directly by our practice. Being in an independent practice allowed us the flexibility to prioritize working with the right team members first, and then structuring the relationship model second. 

 

Lesson 4: Technology Is a Vital Tool in Redesigning Health Care

When I worked in a large academic health system, technology was often seen as an administrative burden rather than a clinical asset. Electronic health records (EHR) and a lot of the other IT systems that health care workers and patients interacted with on a regular basis were viewed as a barrier to care or a cause of time burdens instead of as tools to make health care easier. As we built our new practice from scratch, it was critical that we had an IT infrastructure that aligned with our core goals: simplify and automate the health care experience for everyone.

For our practice, we didn’t try to re-invent the wheel. Instead we copied from other industries who had already figured out a great solution for a problem we had. We wanted our patients to have a great customer service experience when interacting with our practice for scheduling, questions, refills, etc. So we implemented a unified communication system that some Fortune 100 companies, with perennial high scores for customer service, used. We wanted a great human resource system that would streamline the administrative time it would take to handle all HR needs for our practice. So we implemented an HR information system that had the best ratings for automation and integration with other business systems. At every point in the process, we reminded ourselves to focus on simplification and automation for every user of the system. 

 

Conclusion: A Rewarding Transition

The decision to leave academic medicine and start an independent gastroenterology practice wasn’t easy, but it was one of the most rewarding choices I have made. The lessons I’ve learned along the way — embracing autonomy, understanding financial stewardship, fostering collaboration, and leveraging technology — have helped me work toward a better total health care experience for the community.

This journey has also been deeply fulfilling on a personal level. It has allowed me to build stronger relationships with my patients, focus on long-term health outcomes, and create a practice where innovation and quality truly matter. While the challenges of running a private practice are real, the rewards — both for me and my patients — are immeasurable. If I had to do it all over again, I wouldn’t hesitate for a moment. If anything, I should have done it earlier.

Dr. Gupta is Managing Partner at Midwest Digestive Health & Nutrition, in Des Plaines, Illinois. He has reported no conflicts of interest in relation to this article.

After more than 10 years of serving in a large academic medical center in Chicago, Illinois, that was part of a national health care system, the decision to transition into private practice wasn’t one I made lightly.

Having built a rewarding career and spent over a quarter of my life in an academic medical center and a national health system, the move to starting an independent practice from scratch was both exciting and daunting. The notion of leaving behind the structure, resources, and safety of the large health system was unsettling. However, as the landscape of health care continues to evolve, with worsening large structural problems within the U.S. health care system, I realized that starting an independent gastroenterology practice — focused on trying to fix some of these large-scale problems from the start — would not only align with my professional goals but also provide the personal satisfaction I had failed to find. 

As I reflect on my journey, there are a few key lessons I learned from making this leap — lessons that helped me transition from a highly structured employed physician environment to leading a thriving independent practice focused on redesigning gastroenterology care from scratch.

Lesson 1: Autonomy Opens the Door to Innovation

One of the primary reasons I left the employed physician setting was to gain greater control over my clinical practice and decision-making processes.

In a national health care system, the goal of standardization often dictates not only clinical care, but many “back end” aspects of the entire health care experience. We often see the things that are more visible, such as what supplies/equipment you use, how your patient appointments are scheduled, how many support staff members are assigned to help your practice, what electronic health record system you use, and how shared resources (like GI lab block time or anesthesia teams) are allocated.

However, this also impacts things we don’t usually see, such as what fees are billed for care you are providing (like facility fees), communication systems that your patients need to navigate for help, human resource systems you use, and retirement/health benefits you and your other team members receive. 

Standardization has two adverse consequences: 1) it does not allow for personalization and as a result, 2) it suppresses innovation. Standard protocols can streamline processes, but they sometimes fail to account for the nuanced differences between patients, such as genetic factors, unique medical histories, or responses/failures to prior treatments. This rigidity can stifle innovation, as physicians are often bound by guidelines that may not reflect the latest advancements or allow for creative, individualized approaches to care. In the long term, an overemphasis on standardization risks turning health care into a one-size-fits-all model, undermining the potential for breakthroughs.

The transition was challenging at first, as we needed to engage our entire new practice with a different mindset now that many of us had autonomy for the first time. Instead of everyone just practicing health care the way they had done before, we took a page from Elon Musk and challenged every member of the team to ask three questions about everything they do on a daily basis:

• Is what I am doing helping a patient get healthy? (Question every requirement)
• If not, do I still need to do this? (Delete any part of the process you can)
• If so, how can I make this easier, faster, or automated? (Simplify and optimize, accelerate cycle time, and automate)

The freedom to innovate is a hallmark of independent practice. Embracing innovation in every aspect of the practice has been the most critical lesson of this journey. 

 

Lesson 2: Financial Stewardship is Critical for Sustainability

Running an independent practice is not just about medicine — it’s also about managing a business.

This was a stark shift from the large academic health systems, where financial decisions were handled by the “administration.” In my new role as a business owner, understanding the financial aspects of health care was crucial for success. The cost of what patients pay for health care in the United States (either directly in deductibles and coinsurance or indirectly through insurance premiums) is unsustainably high. However, inflation continues to cause substantial increases in almost all the costs of delivering care: medical supplies, salaries, benefits, IT costs, etc. It was critical to develop a financial plan that accounted for these two macro-economic trends, and ideally helped solve for both. In our case, delivering high quality care with a lower cost to patients and payers. 

We started by reevaluating our relationship with payers. Whereas being part of a large academic health system, we are often taught to look at payers as the adversary; as an independent practice looking to redesign the health care experience, it was critical for us to look to the payers as a partner in this journey. Understanding payer expectations and structuring contracts that aligned with shared goals of reducing total health care costs for patients was one of the foundations of our financial plan. 

Offering office-based endoscopy was one innovation we implemented to significantly impact both patient affordability and practice revenue. By performing procedures like colonoscopies and upper endoscopies in an office setting rather than a hospital or ambulatory surgery center, we eliminated facility fees, which are often a significant part of the total cost of care. This directly lowers out-of-pocket expenses for patients and reduces the overall financial burden on insurance companies. At the same time, it allows the practice to capture more of the revenue from these procedures, without the overhead costs associated with larger facilities. This model creates a win-win situation: patients save money while receiving the same quality of care, and the practice experiences an increase in profitability and autonomy in managing its services.

 

Lesson 3: Collaborative Care and Multidisciplinary Teams Can Exist Anywhere

One aspect I deeply valued in academia was the collaborative environment — having specialists across disciplines work together on challenging cases. In private practice, I was concerned that I would lose this collegial atmosphere. However, I quickly learned that building a robust network of multidisciplinary collaborators was achievable in independent practice, just like it was in a large health system.

In our practice, we established close relationships with primary care physicians, surgeons, advanced practice providers, dietitians, behavioral health specialists, and others. These partnerships were not just referral networks but integrated care teams where communication and shared decision-making were prioritized. By fostering collaboration, we could offer patients comprehensive care that addressed their physical, psychological, and nutritional needs. 

For example, managing patients with chronic conditions like inflammatory bowel disease, cirrhosis, or obesity requires more than just prescribing medications. It involves regular monitoring, dietary adjustments, psychological support, and in some cases, surgical intervention. In an academic setting, coordinating this level of care can be cumbersome due to institutional barriers and siloed departments. In our practice, some of these relationships are achieved through partnerships with other like-minded practices. In other situations, team members of other disciplines are employed directly by our practice. Being in an independent practice allowed us the flexibility to prioritize working with the right team members first, and then structuring the relationship model second. 

 

Lesson 4: Technology Is a Vital Tool in Redesigning Health Care

When I worked in a large academic health system, technology was often seen as an administrative burden rather than a clinical asset. Electronic health records (EHR) and a lot of the other IT systems that health care workers and patients interacted with on a regular basis were viewed as a barrier to care or a cause of time burdens instead of as tools to make health care easier. As we built our new practice from scratch, it was critical that we had an IT infrastructure that aligned with our core goals: simplify and automate the health care experience for everyone.

For our practice, we didn’t try to re-invent the wheel. Instead we copied from other industries who had already figured out a great solution for a problem we had. We wanted our patients to have a great customer service experience when interacting with our practice for scheduling, questions, refills, etc. So we implemented a unified communication system that some Fortune 100 companies, with perennial high scores for customer service, used. We wanted a great human resource system that would streamline the administrative time it would take to handle all HR needs for our practice. So we implemented an HR information system that had the best ratings for automation and integration with other business systems. At every point in the process, we reminded ourselves to focus on simplification and automation for every user of the system. 

 

Conclusion: A Rewarding Transition

The decision to leave academic medicine and start an independent gastroenterology practice wasn’t easy, but it was one of the most rewarding choices I have made. The lessons I’ve learned along the way — embracing autonomy, understanding financial stewardship, fostering collaboration, and leveraging technology — have helped me work toward a better total health care experience for the community.

This journey has also been deeply fulfilling on a personal level. It has allowed me to build stronger relationships with my patients, focus on long-term health outcomes, and create a practice where innovation and quality truly matter. While the challenges of running a private practice are real, the rewards — both for me and my patients — are immeasurable. If I had to do it all over again, I wouldn’t hesitate for a moment. If anything, I should have done it earlier.

Dr. Gupta is Managing Partner at Midwest Digestive Health & Nutrition, in Des Plaines, Illinois. He has reported no conflicts of interest in relation to this article.