Federal Practitioner

SAN ANTONIO — Axillary lymph node dissection may be unnecessary if breast cancer patients with one or two positive sentinel lymph nodes plan to have adjuvant nodal radiation, according to a major Scandinavian trial presented at the San Antonio Breast Cancer Symposium.

“It means that you don’t need to dissect the axilla if you” are going to “radiate the axilla.” “For the U.S., that’s the conclusion because there are still centers that do both, and that’s out,” lead investigator Jana de Boniface, MD, PhD, a breast cancer surgeon at the Karolinska Institutet, Stockholm, said in an interview.

The study added to a persistent theme at this year’s meeting, protecting breast cancer patients from doing too much and causing unnecessary harm. Some even wondered if 5 years of endocrine therapy is necessary.

Dr. Boniface shared her thoughts after presenting the Scandinavian trial, SENOMAC, which she led.

SENOMAC randomized 1,204 patients with one or two positive sentinel lymph nodes to axillary dissection; 1,335 with the same finding were randomized to no dissection.

Subjects had clinically T1-3, N0 primary breast cancer. About 89% in both arms went on to adjuvant radiation, including nodal radiation, and almost all also went on to systemic therapy, which included endocrine therapy in over 90%. Only about 2% of subjects had neoadjuvant therapy.

At a median follow-up of nearly 4 years, recurrence-free survival was virtually identical in both groups, with 8% of patients in the dissection arm and 7.1% in the no-dissection group having recurrences. Estimated 5-year recurrence-free survival was just shy of 90% in both groups. Skipping dissection was strongly non-inferior to having one (P < .001).

SENOMAC “clearly shows that you don’t need to dissect the axilla if you have one to two positive sentinel lymph nodes” so long as patients have adjuvant nodal radiation. Recurrence-free survival “curves practically overlap, and we cannot see any difference between the two groups,” Dr. Boniface said.

Meanwhile, the dissection group fared worse on patient reported outcomes. Overall survival outcomes, the primary endpoint of the trial, are expected within 2 years.

The goal of the trial, the largest to date to look into the issue, was to fill gaps in the literature. Similar outcomes were reported around a decade ago in patients with low sentinel lymph node burdens, but the extensive exclusion criteria raised questions about general applicability.

In contrast, SENOMAC was widely inclusive. Over a third of patients had mastectomies, over a third had sentinel lymph node extracapsular extension, almost 6% had T3 disease, almost 20% had lobular carcinoma, 40% were 65 years or older, and tumors were as large as 15.5 cm.

The findings held regardless of those and other factors on subgroup analyses, including estrogen receptor and HER2 status and the number of additional positive nodes retrieved in the dissection group.

Andrea V. Barrio, MD, the study discussant and a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York, agreed with the message from SENOMAC.

“Based on this, ALND [axillary lymph node dissection] should not be considered standard in patients with clinical T1-3, N0 breast cancer with one to two positive sentinel nodes, with or without microscopic extracapsular extension, undergoing lumpectomy or mastectomy,” provided nodal adjuvant radiotherapy is indicated, she said.

Although adjuvant nodal radiation for patients with one to three positive sentinel nodes is standard of care in Denmark and Sweden, where most of the patients in SENOMAC were located, practices vary widely in the United States. If adjuvant radiation isn’t used, “then ALND [is still] indicated,” Dr. Barrio said, but in either case, “only one is needed.”

In keeping with the de-escalation theme at the 2023 symposium, both Dr. Boniface and Dr. Barrio noted that trials are now underway to find patients who can avoid any axillary treatment at all if they have just one or two positive sentinel lymph nodes.

Preoperative axillary ultrasound was mandatory in SENOMAC and patients with non-palpable suspicious axillary lymph nodes were enrolled.

Thirty-six were positive on fine needle aspiration and randomized into the study, but when asked, Dr. Boniface didn’t have the data immediately at hand on how they fared.

The work was funded by the Swedish Research Council, Nordic Cancer Union, and others. Dr. Boniface and Dr. Barrio didn’t have any disclosures.

SAN ANTONIO — Axillary lymph node dissection may be unnecessary if breast cancer patients with one or two positive sentinel lymph nodes plan to have adjuvant nodal radiation, according to a major Scandinavian trial presented at the San Antonio Breast Cancer Symposium.

“It means that you don’t need to dissect the axilla if you” are going to “radiate the axilla.” “For the U.S., that’s the conclusion because there are still centers that do both, and that’s out,” lead investigator Jana de Boniface, MD, PhD, a breast cancer surgeon at the Karolinska Institutet, Stockholm, said in an interview.

The study added to a persistent theme at this year’s meeting, protecting breast cancer patients from doing too much and causing unnecessary harm. Some even wondered if 5 years of endocrine therapy is necessary.

Dr. Boniface shared her thoughts after presenting the Scandinavian trial, SENOMAC, which she led.

SENOMAC randomized 1,204 patients with one or two positive sentinel lymph nodes to axillary dissection; 1,335 with the same finding were randomized to no dissection.

Subjects had clinically T1-3, N0 primary breast cancer. About 89% in both arms went on to adjuvant radiation, including nodal radiation, and almost all also went on to systemic therapy, which included endocrine therapy in over 90%. Only about 2% of subjects had neoadjuvant therapy.

At a median follow-up of nearly 4 years, recurrence-free survival was virtually identical in both groups, with 8% of patients in the dissection arm and 7.1% in the no-dissection group having recurrences. Estimated 5-year recurrence-free survival was just shy of 90% in both groups. Skipping dissection was strongly non-inferior to having one (P < .001).

SENOMAC “clearly shows that you don’t need to dissect the axilla if you have one to two positive sentinel lymph nodes” so long as patients have adjuvant nodal radiation. Recurrence-free survival “curves practically overlap, and we cannot see any difference between the two groups,” Dr. Boniface said.

Meanwhile, the dissection group fared worse on patient reported outcomes. Overall survival outcomes, the primary endpoint of the trial, are expected within 2 years.

The goal of the trial, the largest to date to look into the issue, was to fill gaps in the literature. Similar outcomes were reported around a decade ago in patients with low sentinel lymph node burdens, but the extensive exclusion criteria raised questions about general applicability.

In contrast, SENOMAC was widely inclusive. Over a third of patients had mastectomies, over a third had sentinel lymph node extracapsular extension, almost 6% had T3 disease, almost 20% had lobular carcinoma, 40% were 65 years or older, and tumors were as large as 15.5 cm.

The findings held regardless of those and other factors on subgroup analyses, including estrogen receptor and HER2 status and the number of additional positive nodes retrieved in the dissection group.

Andrea V. Barrio, MD, the study discussant and a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York, agreed with the message from SENOMAC.

“Based on this, ALND [axillary lymph node dissection] should not be considered standard in patients with clinical T1-3, N0 breast cancer with one to two positive sentinel nodes, with or without microscopic extracapsular extension, undergoing lumpectomy or mastectomy,” provided nodal adjuvant radiotherapy is indicated, she said.

Although adjuvant nodal radiation for patients with one to three positive sentinel nodes is standard of care in Denmark and Sweden, where most of the patients in SENOMAC were located, practices vary widely in the United States. If adjuvant radiation isn’t used, “then ALND [is still] indicated,” Dr. Barrio said, but in either case, “only one is needed.”

In keeping with the de-escalation theme at the 2023 symposium, both Dr. Boniface and Dr. Barrio noted that trials are now underway to find patients who can avoid any axillary treatment at all if they have just one or two positive sentinel lymph nodes.

Preoperative axillary ultrasound was mandatory in SENOMAC and patients with non-palpable suspicious axillary lymph nodes were enrolled.

Thirty-six were positive on fine needle aspiration and randomized into the study, but when asked, Dr. Boniface didn’t have the data immediately at hand on how they fared.

The work was funded by the Swedish Research Council, Nordic Cancer Union, and others. Dr. Boniface and Dr. Barrio didn’t have any disclosures.

SAN ANTONIO — Axillary lymph node dissection may be unnecessary if breast cancer patients with one or two positive sentinel lymph nodes plan to have adjuvant nodal radiation, according to a major Scandinavian trial presented at the San Antonio Breast Cancer Symposium.

“It means that you don’t need to dissect the axilla if you” are going to “radiate the axilla.” “For the U.S., that’s the conclusion because there are still centers that do both, and that’s out,” lead investigator Jana de Boniface, MD, PhD, a breast cancer surgeon at the Karolinska Institutet, Stockholm, said in an interview.

The study added to a persistent theme at this year’s meeting, protecting breast cancer patients from doing too much and causing unnecessary harm. Some even wondered if 5 years of endocrine therapy is necessary.

Dr. Boniface shared her thoughts after presenting the Scandinavian trial, SENOMAC, which she led.

SENOMAC randomized 1,204 patients with one or two positive sentinel lymph nodes to axillary dissection; 1,335 with the same finding were randomized to no dissection.

Subjects had clinically T1-3, N0 primary breast cancer. About 89% in both arms went on to adjuvant radiation, including nodal radiation, and almost all also went on to systemic therapy, which included endocrine therapy in over 90%. Only about 2% of subjects had neoadjuvant therapy.

At a median follow-up of nearly 4 years, recurrence-free survival was virtually identical in both groups, with 8% of patients in the dissection arm and 7.1% in the no-dissection group having recurrences. Estimated 5-year recurrence-free survival was just shy of 90% in both groups. Skipping dissection was strongly non-inferior to having one (P < .001).

SENOMAC “clearly shows that you don’t need to dissect the axilla if you have one to two positive sentinel lymph nodes” so long as patients have adjuvant nodal radiation. Recurrence-free survival “curves practically overlap, and we cannot see any difference between the two groups,” Dr. Boniface said.

Meanwhile, the dissection group fared worse on patient reported outcomes. Overall survival outcomes, the primary endpoint of the trial, are expected within 2 years.

The goal of the trial, the largest to date to look into the issue, was to fill gaps in the literature. Similar outcomes were reported around a decade ago in patients with low sentinel lymph node burdens, but the extensive exclusion criteria raised questions about general applicability.

In contrast, SENOMAC was widely inclusive. Over a third of patients had mastectomies, over a third had sentinel lymph node extracapsular extension, almost 6% had T3 disease, almost 20% had lobular carcinoma, 40% were 65 years or older, and tumors were as large as 15.5 cm.

The findings held regardless of those and other factors on subgroup analyses, including estrogen receptor and HER2 status and the number of additional positive nodes retrieved in the dissection group.

Andrea V. Barrio, MD, the study discussant and a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York, agreed with the message from SENOMAC.

“Based on this, ALND [axillary lymph node dissection] should not be considered standard in patients with clinical T1-3, N0 breast cancer with one to two positive sentinel nodes, with or without microscopic extracapsular extension, undergoing lumpectomy or mastectomy,” provided nodal adjuvant radiotherapy is indicated, she said.

Although adjuvant nodal radiation for patients with one to three positive sentinel nodes is standard of care in Denmark and Sweden, where most of the patients in SENOMAC were located, practices vary widely in the United States. If adjuvant radiation isn’t used, “then ALND [is still] indicated,” Dr. Barrio said, but in either case, “only one is needed.”

In keeping with the de-escalation theme at the 2023 symposium, both Dr. Boniface and Dr. Barrio noted that trials are now underway to find patients who can avoid any axillary treatment at all if they have just one or two positive sentinel lymph nodes.

Preoperative axillary ultrasound was mandatory in SENOMAC and patients with non-palpable suspicious axillary lymph nodes were enrolled.

Thirty-six were positive on fine needle aspiration and randomized into the study, but when asked, Dr. Boniface didn’t have the data immediately at hand on how they fared.

The work was funded by the Swedish Research Council, Nordic Cancer Union, and others. Dr. Boniface and Dr. Barrio didn’t have any disclosures.

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Watto, here with America’s primary care physician, Dr. Paul Nelson Williams. Paul, are you ready to talk about some adrenal insufficiency? We had a great conversation with Dr. Atil Kargi, and I’d like you to start us off.

Paul N. Williams, MD: How about thinking about it? It’s a good place to start.

That’s one of the ways this episode changed my approach a little bit. I never really thought about the fact that many patients present for evaluation of adrenal insufficiency from gastroenterology clinics. It’s such a protean sort of nonspecific presentation. But if you have someone with chronic malaise and poor appetite and maybe unexplained weight loss, and your GI workup is not really leading you anywhere, it’s probably worth thinking about adrenal insufficiency. Even though primary adrenal insufficiency is pretty rare — we’re talking cases per millions — secondary adrenal insufficiency is actually fairly common. It’s probably worth thinking about and testing for more often than I have in the past. So for me, it’s having a lower threshold to start looking for it.

Dr. Watto: When it’s adrenal crisis, you probably think about it, but then it’s too late. Ideally, you would think about it before that happens. But the symptoms can be quite vague. The mineralocorticoid symptoms, like salt cravings, dizziness, near syncope, muscle cramps, might make me think of it because they sound more like something endocrine is going on. But if it’s just a little weight loss, a little fatigue, or a little nausea, that’s everybody.

Dr. Williams: Right. If a patient came to me saying, “I’m craving salt,” that might hasten the workup a little bit, but that’s not the typical presentation.

Dr. Watto: If you are going to check a cortisol level, you should really check it in the morning, between 7 AM and 9 AM. If you check it too early, it might not have peaked yet, so you might get a level that looks low. But if you had checked an hour or 2 later, it might have been above a threshold, and then you would know you could rule out the diagnosis. The cutoffs depend on your source:  < 3-5 µg/dL that early in the morning is pretty much diagnostic of adrenal insufficiency. If it’s > 15 µg/dL, that’s a pretty robust cortisol and the patient probably doesn’t have adrenal insufficiency. But if the level is between 5 µg/dL and 15 µg/dL, you’re in a gray zone, and that’s where you might think about doing a stimulation (stim) test.

Dr. Kargi gave us a quick and dirty version of the stim test. Paul, have you had a chance to try this yet?

Dr. Williams: I have not. Have you? I’m sure you’ve been just waiting for the chance.

Dr. Watto: I would love to do this. I don›t know whether I›m set up to do it in the office right now. But this is an aspirational goal for my practice, and I›m sure some physicians are set up in their office already to do it. You can give either intramuscular or subcutaneous cosyntropin 250 µg. You don›t even have to get a baseline cortisol level right before the injection. Let›s say the patient›s previous cortisol level was between 5 µg/dL and 15 µg/dL, so you weren›t sure about the diagnosis. You bring them back to the office one day, give them a shot of cosyntropin, and then 30-60 minutes later, have a random cortisol drawn. If it›s > 19 µg/dL, you›ve ruled out adrenal insufficiency. If it›s anything else, send them to an endocrinologist to sort it out. You might be able to make the diagnosis yourself doing that.

Any treatment pearls to leave the audience with?

Dr. Williams: I hope endocrinologists don›t take issue with this. I say this with respect and admiration, but it feels kind of vibe-based to me. Without a lab value to guide treatment, you are dependent on the patient telling you how they feel much of the time. You have to let their symptoms guide you. It is probably worth noting that because hydrocortisone has a relatively short half-life, within hours, in fact, you typically have to do twice-daily dosing, sometimes even three times daily dosing to get patients to where they feel okay. It sounds like there›s a fair amount of trial and error and some adjustments that you have to make depending on what›s going on with the patient at any given time. You land somewhere between a dose of 15-30 mg per day, but there will be some variability, even within an individual patient, depending on what›s going on with them from a physiologic standpoint.

Dr. Watto: They are going to take one dose in the morning and then a second dose in the afternoon, but they don’t want them to take it too late in the evening because it could cause insomnia, and you want to try to mimic physiologic levels as much as you can. Two thirds of the daily dose is given early in the morning and then another third of the daily dose later in the day if you are prescribing two times daily dosing.

And Dr. Kargi had a low threshold for doubling the dose. If the patient has a cold, double the dose for 2 or 3 days. With a high fever, triple the dose for a few days. If they are going for surgery, they are probably going to be getting some intravenous hydrocortisone while they’re in the hospital.

We really turned over like every stone we could possibly think of on this podcast. There were so many great pearls that we don’t have time to go through them all here. But we talked about steroid tapers and a lot more. You can check it out here.

Dr. Watto has disclosed no relevant financial relationships.

Dr. Williams has disclosed the following relevant financial relationships:Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: The CurbsidersReceived income in an amount equal to or greater than $250 from: The Curbsiders.

A version of this article appeared on Medscape.com.

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Watto, here with America’s primary care physician, Dr. Paul Nelson Williams. Paul, are you ready to talk about some adrenal insufficiency? We had a great conversation with Dr. Atil Kargi, and I’d like you to start us off.

Paul N. Williams, MD: How about thinking about it? It’s a good place to start.

That’s one of the ways this episode changed my approach a little bit. I never really thought about the fact that many patients present for evaluation of adrenal insufficiency from gastroenterology clinics. It’s such a protean sort of nonspecific presentation. But if you have someone with chronic malaise and poor appetite and maybe unexplained weight loss, and your GI workup is not really leading you anywhere, it’s probably worth thinking about adrenal insufficiency. Even though primary adrenal insufficiency is pretty rare — we’re talking cases per millions — secondary adrenal insufficiency is actually fairly common. It’s probably worth thinking about and testing for more often than I have in the past. So for me, it’s having a lower threshold to start looking for it.

Dr. Watto: When it’s adrenal crisis, you probably think about it, but then it’s too late. Ideally, you would think about it before that happens. But the symptoms can be quite vague. The mineralocorticoid symptoms, like salt cravings, dizziness, near syncope, muscle cramps, might make me think of it because they sound more like something endocrine is going on. But if it’s just a little weight loss, a little fatigue, or a little nausea, that’s everybody.

Dr. Williams: Right. If a patient came to me saying, “I’m craving salt,” that might hasten the workup a little bit, but that’s not the typical presentation.

Dr. Watto: If you are going to check a cortisol level, you should really check it in the morning, between 7 AM and 9 AM. If you check it too early, it might not have peaked yet, so you might get a level that looks low. But if you had checked an hour or 2 later, it might have been above a threshold, and then you would know you could rule out the diagnosis. The cutoffs depend on your source:  < 3-5 µg/dL that early in the morning is pretty much diagnostic of adrenal insufficiency. If it’s > 15 µg/dL, that’s a pretty robust cortisol and the patient probably doesn’t have adrenal insufficiency. But if the level is between 5 µg/dL and 15 µg/dL, you’re in a gray zone, and that’s where you might think about doing a stimulation (stim) test.

Dr. Kargi gave us a quick and dirty version of the stim test. Paul, have you had a chance to try this yet?

Dr. Williams: I have not. Have you? I’m sure you’ve been just waiting for the chance.

Dr. Watto: I would love to do this. I don›t know whether I›m set up to do it in the office right now. But this is an aspirational goal for my practice, and I›m sure some physicians are set up in their office already to do it. You can give either intramuscular or subcutaneous cosyntropin 250 µg. You don›t even have to get a baseline cortisol level right before the injection. Let›s say the patient›s previous cortisol level was between 5 µg/dL and 15 µg/dL, so you weren›t sure about the diagnosis. You bring them back to the office one day, give them a shot of cosyntropin, and then 30-60 minutes later, have a random cortisol drawn. If it›s > 19 µg/dL, you›ve ruled out adrenal insufficiency. If it›s anything else, send them to an endocrinologist to sort it out. You might be able to make the diagnosis yourself doing that.

Any treatment pearls to leave the audience with?

Dr. Williams: I hope endocrinologists don›t take issue with this. I say this with respect and admiration, but it feels kind of vibe-based to me. Without a lab value to guide treatment, you are dependent on the patient telling you how they feel much of the time. You have to let their symptoms guide you. It is probably worth noting that because hydrocortisone has a relatively short half-life, within hours, in fact, you typically have to do twice-daily dosing, sometimes even three times daily dosing to get patients to where they feel okay. It sounds like there›s a fair amount of trial and error and some adjustments that you have to make depending on what›s going on with the patient at any given time. You land somewhere between a dose of 15-30 mg per day, but there will be some variability, even within an individual patient, depending on what›s going on with them from a physiologic standpoint.

Dr. Watto: They are going to take one dose in the morning and then a second dose in the afternoon, but they don’t want them to take it too late in the evening because it could cause insomnia, and you want to try to mimic physiologic levels as much as you can. Two thirds of the daily dose is given early in the morning and then another third of the daily dose later in the day if you are prescribing two times daily dosing.

And Dr. Kargi had a low threshold for doubling the dose. If the patient has a cold, double the dose for 2 or 3 days. With a high fever, triple the dose for a few days. If they are going for surgery, they are probably going to be getting some intravenous hydrocortisone while they’re in the hospital.

We really turned over like every stone we could possibly think of on this podcast. There were so many great pearls that we don’t have time to go through them all here. But we talked about steroid tapers and a lot more. You can check it out here.

Dr. Watto has disclosed no relevant financial relationships.

Dr. Williams has disclosed the following relevant financial relationships:Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: The CurbsidersReceived income in an amount equal to or greater than $250 from: The Curbsiders.

A version of this article appeared on Medscape.com.

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Watto, here with America’s primary care physician, Dr. Paul Nelson Williams. Paul, are you ready to talk about some adrenal insufficiency? We had a great conversation with Dr. Atil Kargi, and I’d like you to start us off.

Paul N. Williams, MD: How about thinking about it? It’s a good place to start.

That’s one of the ways this episode changed my approach a little bit. I never really thought about the fact that many patients present for evaluation of adrenal insufficiency from gastroenterology clinics. It’s such a protean sort of nonspecific presentation. But if you have someone with chronic malaise and poor appetite and maybe unexplained weight loss, and your GI workup is not really leading you anywhere, it’s probably worth thinking about adrenal insufficiency. Even though primary adrenal insufficiency is pretty rare — we’re talking cases per millions — secondary adrenal insufficiency is actually fairly common. It’s probably worth thinking about and testing for more often than I have in the past. So for me, it’s having a lower threshold to start looking for it.

Dr. Watto: When it’s adrenal crisis, you probably think about it, but then it’s too late. Ideally, you would think about it before that happens. But the symptoms can be quite vague. The mineralocorticoid symptoms, like salt cravings, dizziness, near syncope, muscle cramps, might make me think of it because they sound more like something endocrine is going on. But if it’s just a little weight loss, a little fatigue, or a little nausea, that’s everybody.

Dr. Williams: Right. If a patient came to me saying, “I’m craving salt,” that might hasten the workup a little bit, but that’s not the typical presentation.

Dr. Watto: If you are going to check a cortisol level, you should really check it in the morning, between 7 AM and 9 AM. If you check it too early, it might not have peaked yet, so you might get a level that looks low. But if you had checked an hour or 2 later, it might have been above a threshold, and then you would know you could rule out the diagnosis. The cutoffs depend on your source:  < 3-5 µg/dL that early in the morning is pretty much diagnostic of adrenal insufficiency. If it’s > 15 µg/dL, that’s a pretty robust cortisol and the patient probably doesn’t have adrenal insufficiency. But if the level is between 5 µg/dL and 15 µg/dL, you’re in a gray zone, and that’s where you might think about doing a stimulation (stim) test.

Dr. Kargi gave us a quick and dirty version of the stim test. Paul, have you had a chance to try this yet?

Dr. Williams: I have not. Have you? I’m sure you’ve been just waiting for the chance.

Dr. Watto: I would love to do this. I don›t know whether I›m set up to do it in the office right now. But this is an aspirational goal for my practice, and I›m sure some physicians are set up in their office already to do it. You can give either intramuscular or subcutaneous cosyntropin 250 µg. You don›t even have to get a baseline cortisol level right before the injection. Let›s say the patient›s previous cortisol level was between 5 µg/dL and 15 µg/dL, so you weren›t sure about the diagnosis. You bring them back to the office one day, give them a shot of cosyntropin, and then 30-60 minutes later, have a random cortisol drawn. If it›s > 19 µg/dL, you›ve ruled out adrenal insufficiency. If it›s anything else, send them to an endocrinologist to sort it out. You might be able to make the diagnosis yourself doing that.

Any treatment pearls to leave the audience with?

Dr. Williams: I hope endocrinologists don›t take issue with this. I say this with respect and admiration, but it feels kind of vibe-based to me. Without a lab value to guide treatment, you are dependent on the patient telling you how they feel much of the time. You have to let their symptoms guide you. It is probably worth noting that because hydrocortisone has a relatively short half-life, within hours, in fact, you typically have to do twice-daily dosing, sometimes even three times daily dosing to get patients to where they feel okay. It sounds like there›s a fair amount of trial and error and some adjustments that you have to make depending on what›s going on with the patient at any given time. You land somewhere between a dose of 15-30 mg per day, but there will be some variability, even within an individual patient, depending on what›s going on with them from a physiologic standpoint.

Dr. Watto: They are going to take one dose in the morning and then a second dose in the afternoon, but they don’t want them to take it too late in the evening because it could cause insomnia, and you want to try to mimic physiologic levels as much as you can. Two thirds of the daily dose is given early in the morning and then another third of the daily dose later in the day if you are prescribing two times daily dosing.

And Dr. Kargi had a low threshold for doubling the dose. If the patient has a cold, double the dose for 2 or 3 days. With a high fever, triple the dose for a few days. If they are going for surgery, they are probably going to be getting some intravenous hydrocortisone while they’re in the hospital.

We really turned over like every stone we could possibly think of on this podcast. There were so many great pearls that we don’t have time to go through them all here. But we talked about steroid tapers and a lot more. You can check it out here.

Dr. Watto has disclosed no relevant financial relationships.

Dr. Williams has disclosed the following relevant financial relationships:Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: The CurbsidersReceived income in an amount equal to or greater than $250 from: The Curbsiders.

A version of this article appeared on Medscape.com.

TOPLINE:

Consuming nonsugar sweeteners (NSS) leads to significant changes in both stool and duodenal microbial diversity and composition and levels of circulating inflammatory markers.

METHODOLOGY:

• Researchers analyzed samples from the REIMAGINE (Revealing the Entire Intestinal Microbiota and its Associations with the Genetic, Immunologic, and Neuroendocrine Ecosystem) study to assess the potential effects of NSS consumption on the duodenal luminal microbiome.
• They analyzed subjects consuming non-aspartame nonsugar sweeteners (NANS; n = 35) and aspartame only (ASP; n = 9), who were compared with 55 control participants matched for age, sex, and body mass index.
• A subset of 40 participants provided stool samples for additional analysis.

TAKEAWAY:

• Duodenal alpha diversity was lower in NANS consumers vs controls.
• Duodenal relative abundance (RA) of Escherichia, Klebsiella, and Salmonella was lower in both NANS and ASP vs controls, whereas stool RA of these phylum Proteobacteria was increased in both NANS and ASP.
• Compared with controls, NANS and ASP differed in how they altered predicted duodenal microbial metabolic pathways, with NANS impacting polysaccharides biosynthesis and D-galactose degradation and ASP significantly enriching biosynthesis of cylindrospermopsin, a potential cancer-causing agent known to adversely impact the liver and nervous system.
• Circulating levels of interleukin (IL)-1b, a pro-inflammatory cytokine that plays a key role in the immune response, were significantly decreased in NANS vs controls, whereas IL-6 and IL-10, two cytokines with protective properties, were decreased in the ASP group vs controls.

IN PRACTICE:

“Given the crucial role played by small intestinal microbes in digestion, nutrient absorption, immune regulation, and endocrine functions, coupled with the substantial prevalence of NSS consumption among US adults (estimated at 41.4%), our findings have potential implications for metabolic and gastrointestinal health in a considerable proportion of the American adult population.”

SOURCE:

The study, conducted by Ava Hosseini, MPH, and colleagues at Cedars-Sinai, Los Angeles, was published online on November 22, 2023, in iScience.

LIMITATIONS:

The study population may not be representative of healthy individuals as they underwent upper endoscopy for various reasons (eg, evaluation of intestinal complaints). After exclusions, the duodenal sample size for the aspartame group was small. Samples were collected at a single timepoint, limiting the ability to establish causal relationships.

DISCLOSURES:

This research was supported by Frank Lee, the Monica Lester Charitable Trust, and the Elias, Genevieve, and Georgianna Atol Charitable Trust through their support of the Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Consuming nonsugar sweeteners (NSS) leads to significant changes in both stool and duodenal microbial diversity and composition and levels of circulating inflammatory markers.

METHODOLOGY:

• Researchers analyzed samples from the REIMAGINE (Revealing the Entire Intestinal Microbiota and its Associations with the Genetic, Immunologic, and Neuroendocrine Ecosystem) study to assess the potential effects of NSS consumption on the duodenal luminal microbiome.
• They analyzed subjects consuming non-aspartame nonsugar sweeteners (NANS; n = 35) and aspartame only (ASP; n = 9), who were compared with 55 control participants matched for age, sex, and body mass index.
• A subset of 40 participants provided stool samples for additional analysis.

TAKEAWAY:

• Duodenal alpha diversity was lower in NANS consumers vs controls.
• Duodenal relative abundance (RA) of Escherichia, Klebsiella, and Salmonella was lower in both NANS and ASP vs controls, whereas stool RA of these phylum Proteobacteria was increased in both NANS and ASP.
• Compared with controls, NANS and ASP differed in how they altered predicted duodenal microbial metabolic pathways, with NANS impacting polysaccharides biosynthesis and D-galactose degradation and ASP significantly enriching biosynthesis of cylindrospermopsin, a potential cancer-causing agent known to adversely impact the liver and nervous system.
• Circulating levels of interleukin (IL)-1b, a pro-inflammatory cytokine that plays a key role in the immune response, were significantly decreased in NANS vs controls, whereas IL-6 and IL-10, two cytokines with protective properties, were decreased in the ASP group vs controls.

IN PRACTICE:

“Given the crucial role played by small intestinal microbes in digestion, nutrient absorption, immune regulation, and endocrine functions, coupled with the substantial prevalence of NSS consumption among US adults (estimated at 41.4%), our findings have potential implications for metabolic and gastrointestinal health in a considerable proportion of the American adult population.”

SOURCE:

The study, conducted by Ava Hosseini, MPH, and colleagues at Cedars-Sinai, Los Angeles, was published online on November 22, 2023, in iScience.

LIMITATIONS:

The study population may not be representative of healthy individuals as they underwent upper endoscopy for various reasons (eg, evaluation of intestinal complaints). After exclusions, the duodenal sample size for the aspartame group was small. Samples were collected at a single timepoint, limiting the ability to establish causal relationships.

DISCLOSURES:

This research was supported by Frank Lee, the Monica Lester Charitable Trust, and the Elias, Genevieve, and Georgianna Atol Charitable Trust through their support of the Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Consuming nonsugar sweeteners (NSS) leads to significant changes in both stool and duodenal microbial diversity and composition and levels of circulating inflammatory markers.

METHODOLOGY:

• Researchers analyzed samples from the REIMAGINE (Revealing the Entire Intestinal Microbiota and its Associations with the Genetic, Immunologic, and Neuroendocrine Ecosystem) study to assess the potential effects of NSS consumption on the duodenal luminal microbiome.
• They analyzed subjects consuming non-aspartame nonsugar sweeteners (NANS; n = 35) and aspartame only (ASP; n = 9), who were compared with 55 control participants matched for age, sex, and body mass index.
• A subset of 40 participants provided stool samples for additional analysis.

TAKEAWAY:

• Duodenal alpha diversity was lower in NANS consumers vs controls.
• Duodenal relative abundance (RA) of Escherichia, Klebsiella, and Salmonella was lower in both NANS and ASP vs controls, whereas stool RA of these phylum Proteobacteria was increased in both NANS and ASP.
• Compared with controls, NANS and ASP differed in how they altered predicted duodenal microbial metabolic pathways, with NANS impacting polysaccharides biosynthesis and D-galactose degradation and ASP significantly enriching biosynthesis of cylindrospermopsin, a potential cancer-causing agent known to adversely impact the liver and nervous system.
• Circulating levels of interleukin (IL)-1b, a pro-inflammatory cytokine that plays a key role in the immune response, were significantly decreased in NANS vs controls, whereas IL-6 and IL-10, two cytokines with protective properties, were decreased in the ASP group vs controls.

IN PRACTICE:

“Given the crucial role played by small intestinal microbes in digestion, nutrient absorption, immune regulation, and endocrine functions, coupled with the substantial prevalence of NSS consumption among US adults (estimated at 41.4%), our findings have potential implications for metabolic and gastrointestinal health in a considerable proportion of the American adult population.”

SOURCE:

The study, conducted by Ava Hosseini, MPH, and colleagues at Cedars-Sinai, Los Angeles, was published online on November 22, 2023, in iScience.

LIMITATIONS:

The study population may not be representative of healthy individuals as they underwent upper endoscopy for various reasons (eg, evaluation of intestinal complaints). After exclusions, the duodenal sample size for the aspartame group was small. Samples were collected at a single timepoint, limiting the ability to establish causal relationships.

DISCLOSURES:

This research was supported by Frank Lee, the Monica Lester Charitable Trust, and the Elias, Genevieve, and Georgianna Atol Charitable Trust through their support of the Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Often known as a “silent killer,” ascending thoracic aortic aneurysms (ATAAs) may grow asymptomatically until they rupture, at which point, mortality is over 90%.

But ATAAs may also carry a potential flip side: Apparent protection against the development of atherosclerotic plaque and by extension, for those who have one, a significantly reduced risk for coronary artery disease and myocardial infarction (MI).

“We noticed in the operating room that many patients we worked on who had an ATAA had pristine arteries, like a teenager’s,” said John Elefteriades, MD, William W.L. Glenn Professor of Cardiothoracic Surgery and former chief of cardiothoracic surgery at Yale University and Yale New Haven Hospital, New Haven, Connecticut. “The same was true of the femoral artery, which we use to hook up to the heart-lung machine.”

Elefteriades and colleagues have been investigating the implications of this association for more than two decades. Many of their studies are highlighted in a recent review of the evidence supporting the protective relationship between ATAAs and the development of atherosclerosis and the possible mechanisms driving the relationship.

“We see four different layers of protection,” said Sandip Mukherjee, MD, medical director of the Aortic Institute at Yale New Haven Hospital and a senior editor of the journal AORTA. Mukherjee collaborated with Elefteriades on many of the studies.

The first layer of protection is lower intima-media thickness, specifically, 0.131 mm lower than in individuals without an ATAA. “It may not seem like very much, but one point can actually translate into a 13%-15% decline in the rate of myocardial infarction or stroke,” Dr. Mukherjee said.

The second layer is lower levels of low-density lipoprotein (LDL) cholesterol. Lower LDL cholesterol levels (75 mg/dL) were associated with increased odds of ATAAs (odds ratio [OR], 1.21), whereas elevated levels (150 mg/dL and 200 mg/dL) were associated with decreased odds of ATAAs (OR, 0.62 and 0.29, respectively).

Lower calcification scores for the coronary arteries are the third layer of protection (6.73 vs 9.36 in one study).

The fourth protective layer is a significantly reduced prevalence of coronary artery disease. A study of individuals with ATAA compared to controls found 61 of those with ATAA had coronary artery disease vs 140 of controls, and 11 vs 83 had experienced an MI. Of note, patients with ATAAs were protected despite having higher body mass indices than controls.

Other MI risk factors such as age increased the risk even among those with an ATAA but, again, much less so than among controls; a multivariable binary logistic regression of data in the team’s review showed that patients with ATAAs were 298, 250, and 232 times less likely to have an MI than if they had a family history of MI, dyslipidemia, or hypertension, respectively.

Why the Protection?

The ligamentum arteriosum separates the ascending from the descending (thoracoabdominal) aorta. ATAAs, located above the ligamentum, tend to be pro-aneurysmal but anti-atherosclerotic. In the descending aorta, below the ligamentum, atherosclerotic aneurysms develop.

The differences between the two sections of the aorta originate in the germ layer in the embryo, Dr. Elefteriades said. “The fundamental difference in tissue of origin translates into marked differences in the character of aneurysms in the different aortic segments.”

What specifically underlies the reduced cardiovascular risk? “We don’t really know, but we think that there may be two possible etiologies,” Dr. Mukherjee said. One hypothesis involves transforming growth factor–beta (TGF-beta), which is overexpressed in patients with ATAA and seems to increase their vulnerability to aneurysms while also conferring protection from coronary disease risk.

Some studies have shown differences in cellular responses to TGF-beta between the thoracic and abdominal aorta, including collagen production and contractility. Others have shown that some patients who have had an MI have polymorphisms that decrease their levels of TGF-beta.

Furthermore, TGF-beta plays a key role in the development of the intimal layer, which could underpin the lack of intimal thickening in patients with ATAA.

But overall, studies have been mixed and challenging to interpret, Dr. Elefteriades and Dr. Mukherjee agreed. TGF-beta has multiple remodeling roles in the body, and it is difficult at this point to isolate its exact role in aortic disease.

Another hypothesis involves matrix metalloproteinases (MMPs), which are dysregulated in patients with ATAA and may confer some protection, Mukherjee said. Several studies have shown higher plasma levels of certain MMPs in patients with ATAAs. MMPs also were found to be elevated in the thoracic aortic walls of patients with ATAA who had an aortic dissection, as well as in the aortic smooth muscle cells in the intima and media.

In addition, some studies have shown increased levels of MMP-2 in the aortas of patients with ATAAs compared with patients with coronary artery disease.

Adding to the mix of possibilities, “We recently found a gene that’s dysregulated in our aneurysm patients that is very intimately related to atherosclerosis,” Dr. Elefteriades said. “But the work is too preliminary to say anything more at this point.”

“It would be fabulous to prove what it is causing this protection,” Dr. Mukherjee added. “But the truth is we don’t know. These are hypotheses.”

“The most important message from our work is that most clinicians need to dissociate an ATAA from the concept of atherosclerosis,” Dr. Elefteriades said. “The ascending aorta is not an atherosclerotic phenomenon.”

How to Manage Patients With ATAA

What does the distinct character of ATAAs mean for patient management? “Finding a drug to treat ATAAs — to prevent growth, rupture, or dissection — has been like a search for the Holy Grail,” Dr. Elefteriades said. “Statins are not necessary, as this is a non-atherosclerotic process. Although sporadic studies have reported beneficial effects from beta-blockers or angiotensin II receptor blockers (ARBs), this has often been based on ‘soft’ evidence, requiring a combination of outcome measures to achieve significance.”

That said, he noted, “The mainstay, common sense treatment is to keep blood pressure controlled. This is usually achieved by a beta-blocker and an ARB, even if the benefit is not via a direct biologic effect on the aneurysmal degenerative process, but via simple hemodynamics — discouraging rupture by keeping pressure in the aorta low.”

Dr. Mukherjee suggested that these patients should be referred to a specialty aneurysm center where their genes will be evaluated, and then the aneurysm will be followed very closely.

“If the aneurysm is larger than 4.5 cm, we screen the patient every single year, and if they have chest pain, we treat them the same way as we treat other aneurysms,” he said. “As a rule of thumb, if the aneurysm reaches 5 cm, it should come out, although the size at which this should happen may differ between 4.5 cm and 5.5 cm, depending on the patient’s body size.”

As for lifestyle management, Dr. Elefteriades said, “Protection from atherosclerosis and MI won’t go away after the aneurysm is removed. We think it’s in the body’s chemistry. But even though it’s very hard for those patients to have a heart attack, we don’t recommend they eat roast beef every night — although I do think they’d be protected from such lifestyle aberrations.”

For now, he added, “Our team is on a hunt to find a drug to treat ascending disease directly and effectively. We have ongoing laboratory experiments with two drugs undergoing investigation at some level. We hope to embark soon on clinical trials.”

‘A Milestone’

James Hamilton Black III, MD, vice chair of the writing committee for the 2022 American College of Cardiology/American Heart Association Aortic Disease Guideline and chief of Division of Vascular Surgery and Endovascular Therapy at Johns Hopkins Medicine, Baltimore, commented on the review and the concept of ATAA’s atherosclerotic protection.

“The association of ascending aortic aneurysms with a lower risk for MI is an interesting one, but it’s probably influenced, at least in part, by the patient population.” That population is at least partially curated since people are coming to an academic center. In addition, Dr. Black noted, “the patients with ATAAs are younger, and so age may be a confounding factor in the analyses. We wouldn’t expect them to have the same burden of atherosclerosis” as older patients.

Nevertheless, he said, “the findings speak to an emerging body of literature suggesting that although the aorta is a single organ, there are certainly different areas, and these would respond quite differently to environmental or genetic or heritable stressors. This isn’t surprising, and there probably are a lot of factors involved.”

Overall, he said, the findings underscore “the precision medicine approaches we need to take with patients with aortic diseases.”

In a commentary on the team’s review article, published in 2022, John G.T. Augoustides, MD, professor of anesthesiology and critical care at the Perelman School of Medicine in Philadelphia, Pennsylvania, suggested that ATAA’s “silver lining” could advance the understanding of thoracic aortic aneurysm (TAA) management, be integrated with the expanding horizons in hereditary thoracic aortic disease, and might be explored in the context of bicuspid aortic valve disease.

Highlighting the “relative absence” of atherosclerosis in ascending aortic aneurysms and its importance is a “milestone in our understanding,” he concluded. “It is likely that future advances in TAAs will be significantly influenced by this observation.”

Dr. Elefteriades, Dr. Mukherjee, and Dr. Black have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Often known as a “silent killer,” ascending thoracic aortic aneurysms (ATAAs) may grow asymptomatically until they rupture, at which point, mortality is over 90%.

But ATAAs may also carry a potential flip side: Apparent protection against the development of atherosclerotic plaque and by extension, for those who have one, a significantly reduced risk for coronary artery disease and myocardial infarction (MI).

“We noticed in the operating room that many patients we worked on who had an ATAA had pristine arteries, like a teenager’s,” said John Elefteriades, MD, William W.L. Glenn Professor of Cardiothoracic Surgery and former chief of cardiothoracic surgery at Yale University and Yale New Haven Hospital, New Haven, Connecticut. “The same was true of the femoral artery, which we use to hook up to the heart-lung machine.”

Elefteriades and colleagues have been investigating the implications of this association for more than two decades. Many of their studies are highlighted in a recent review of the evidence supporting the protective relationship between ATAAs and the development of atherosclerosis and the possible mechanisms driving the relationship.

“We see four different layers of protection,” said Sandip Mukherjee, MD, medical director of the Aortic Institute at Yale New Haven Hospital and a senior editor of the journal AORTA. Mukherjee collaborated with Elefteriades on many of the studies.

The first layer of protection is lower intima-media thickness, specifically, 0.131 mm lower than in individuals without an ATAA. “It may not seem like very much, but one point can actually translate into a 13%-15% decline in the rate of myocardial infarction or stroke,” Dr. Mukherjee said.

The second layer is lower levels of low-density lipoprotein (LDL) cholesterol. Lower LDL cholesterol levels (75 mg/dL) were associated with increased odds of ATAAs (odds ratio [OR], 1.21), whereas elevated levels (150 mg/dL and 200 mg/dL) were associated with decreased odds of ATAAs (OR, 0.62 and 0.29, respectively).

Lower calcification scores for the coronary arteries are the third layer of protection (6.73 vs 9.36 in one study).

The fourth protective layer is a significantly reduced prevalence of coronary artery disease. A study of individuals with ATAA compared to controls found 61 of those with ATAA had coronary artery disease vs 140 of controls, and 11 vs 83 had experienced an MI. Of note, patients with ATAAs were protected despite having higher body mass indices than controls.

Other MI risk factors such as age increased the risk even among those with an ATAA but, again, much less so than among controls; a multivariable binary logistic regression of data in the team’s review showed that patients with ATAAs were 298, 250, and 232 times less likely to have an MI than if they had a family history of MI, dyslipidemia, or hypertension, respectively.

Why the Protection?

The ligamentum arteriosum separates the ascending from the descending (thoracoabdominal) aorta. ATAAs, located above the ligamentum, tend to be pro-aneurysmal but anti-atherosclerotic. In the descending aorta, below the ligamentum, atherosclerotic aneurysms develop.

The differences between the two sections of the aorta originate in the germ layer in the embryo, Dr. Elefteriades said. “The fundamental difference in tissue of origin translates into marked differences in the character of aneurysms in the different aortic segments.”

What specifically underlies the reduced cardiovascular risk? “We don’t really know, but we think that there may be two possible etiologies,” Dr. Mukherjee said. One hypothesis involves transforming growth factor–beta (TGF-beta), which is overexpressed in patients with ATAA and seems to increase their vulnerability to aneurysms while also conferring protection from coronary disease risk.

Some studies have shown differences in cellular responses to TGF-beta between the thoracic and abdominal aorta, including collagen production and contractility. Others have shown that some patients who have had an MI have polymorphisms that decrease their levels of TGF-beta.

Furthermore, TGF-beta plays a key role in the development of the intimal layer, which could underpin the lack of intimal thickening in patients with ATAA.

But overall, studies have been mixed and challenging to interpret, Dr. Elefteriades and Dr. Mukherjee agreed. TGF-beta has multiple remodeling roles in the body, and it is difficult at this point to isolate its exact role in aortic disease.

Another hypothesis involves matrix metalloproteinases (MMPs), which are dysregulated in patients with ATAA and may confer some protection, Mukherjee said. Several studies have shown higher plasma levels of certain MMPs in patients with ATAAs. MMPs also were found to be elevated in the thoracic aortic walls of patients with ATAA who had an aortic dissection, as well as in the aortic smooth muscle cells in the intima and media.

In addition, some studies have shown increased levels of MMP-2 in the aortas of patients with ATAAs compared with patients with coronary artery disease.

Adding to the mix of possibilities, “We recently found a gene that’s dysregulated in our aneurysm patients that is very intimately related to atherosclerosis,” Dr. Elefteriades said. “But the work is too preliminary to say anything more at this point.”

“It would be fabulous to prove what it is causing this protection,” Dr. Mukherjee added. “But the truth is we don’t know. These are hypotheses.”

“The most important message from our work is that most clinicians need to dissociate an ATAA from the concept of atherosclerosis,” Dr. Elefteriades said. “The ascending aorta is not an atherosclerotic phenomenon.”

How to Manage Patients With ATAA

What does the distinct character of ATAAs mean for patient management? “Finding a drug to treat ATAAs — to prevent growth, rupture, or dissection — has been like a search for the Holy Grail,” Dr. Elefteriades said. “Statins are not necessary, as this is a non-atherosclerotic process. Although sporadic studies have reported beneficial effects from beta-blockers or angiotensin II receptor blockers (ARBs), this has often been based on ‘soft’ evidence, requiring a combination of outcome measures to achieve significance.”

That said, he noted, “The mainstay, common sense treatment is to keep blood pressure controlled. This is usually achieved by a beta-blocker and an ARB, even if the benefit is not via a direct biologic effect on the aneurysmal degenerative process, but via simple hemodynamics — discouraging rupture by keeping pressure in the aorta low.”

Dr. Mukherjee suggested that these patients should be referred to a specialty aneurysm center where their genes will be evaluated, and then the aneurysm will be followed very closely.

“If the aneurysm is larger than 4.5 cm, we screen the patient every single year, and if they have chest pain, we treat them the same way as we treat other aneurysms,” he said. “As a rule of thumb, if the aneurysm reaches 5 cm, it should come out, although the size at which this should happen may differ between 4.5 cm and 5.5 cm, depending on the patient’s body size.”

As for lifestyle management, Dr. Elefteriades said, “Protection from atherosclerosis and MI won’t go away after the aneurysm is removed. We think it’s in the body’s chemistry. But even though it’s very hard for those patients to have a heart attack, we don’t recommend they eat roast beef every night — although I do think they’d be protected from such lifestyle aberrations.”

For now, he added, “Our team is on a hunt to find a drug to treat ascending disease directly and effectively. We have ongoing laboratory experiments with two drugs undergoing investigation at some level. We hope to embark soon on clinical trials.”

‘A Milestone’

James Hamilton Black III, MD, vice chair of the writing committee for the 2022 American College of Cardiology/American Heart Association Aortic Disease Guideline and chief of Division of Vascular Surgery and Endovascular Therapy at Johns Hopkins Medicine, Baltimore, commented on the review and the concept of ATAA’s atherosclerotic protection.

“The association of ascending aortic aneurysms with a lower risk for MI is an interesting one, but it’s probably influenced, at least in part, by the patient population.” That population is at least partially curated since people are coming to an academic center. In addition, Dr. Black noted, “the patients with ATAAs are younger, and so age may be a confounding factor in the analyses. We wouldn’t expect them to have the same burden of atherosclerosis” as older patients.

Nevertheless, he said, “the findings speak to an emerging body of literature suggesting that although the aorta is a single organ, there are certainly different areas, and these would respond quite differently to environmental or genetic or heritable stressors. This isn’t surprising, and there probably are a lot of factors involved.”

Overall, he said, the findings underscore “the precision medicine approaches we need to take with patients with aortic diseases.”

In a commentary on the team’s review article, published in 2022, John G.T. Augoustides, MD, professor of anesthesiology and critical care at the Perelman School of Medicine in Philadelphia, Pennsylvania, suggested that ATAA’s “silver lining” could advance the understanding of thoracic aortic aneurysm (TAA) management, be integrated with the expanding horizons in hereditary thoracic aortic disease, and might be explored in the context of bicuspid aortic valve disease.

Highlighting the “relative absence” of atherosclerosis in ascending aortic aneurysms and its importance is a “milestone in our understanding,” he concluded. “It is likely that future advances in TAAs will be significantly influenced by this observation.”

Dr. Elefteriades, Dr. Mukherjee, and Dr. Black have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Often known as a “silent killer,” ascending thoracic aortic aneurysms (ATAAs) may grow asymptomatically until they rupture, at which point, mortality is over 90%.

But ATAAs may also carry a potential flip side: Apparent protection against the development of atherosclerotic plaque and by extension, for those who have one, a significantly reduced risk for coronary artery disease and myocardial infarction (MI).

“We noticed in the operating room that many patients we worked on who had an ATAA had pristine arteries, like a teenager’s,” said John Elefteriades, MD, William W.L. Glenn Professor of Cardiothoracic Surgery and former chief of cardiothoracic surgery at Yale University and Yale New Haven Hospital, New Haven, Connecticut. “The same was true of the femoral artery, which we use to hook up to the heart-lung machine.”

Elefteriades and colleagues have been investigating the implications of this association for more than two decades. Many of their studies are highlighted in a recent review of the evidence supporting the protective relationship between ATAAs and the development of atherosclerosis and the possible mechanisms driving the relationship.

“We see four different layers of protection,” said Sandip Mukherjee, MD, medical director of the Aortic Institute at Yale New Haven Hospital and a senior editor of the journal AORTA. Mukherjee collaborated with Elefteriades on many of the studies.

The first layer of protection is lower intima-media thickness, specifically, 0.131 mm lower than in individuals without an ATAA. “It may not seem like very much, but one point can actually translate into a 13%-15% decline in the rate of myocardial infarction or stroke,” Dr. Mukherjee said.

The second layer is lower levels of low-density lipoprotein (LDL) cholesterol. Lower LDL cholesterol levels (75 mg/dL) were associated with increased odds of ATAAs (odds ratio [OR], 1.21), whereas elevated levels (150 mg/dL and 200 mg/dL) were associated with decreased odds of ATAAs (OR, 0.62 and 0.29, respectively).

Lower calcification scores for the coronary arteries are the third layer of protection (6.73 vs 9.36 in one study).

The fourth protective layer is a significantly reduced prevalence of coronary artery disease. A study of individuals with ATAA compared to controls found 61 of those with ATAA had coronary artery disease vs 140 of controls, and 11 vs 83 had experienced an MI. Of note, patients with ATAAs were protected despite having higher body mass indices than controls.

Other MI risk factors such as age increased the risk even among those with an ATAA but, again, much less so than among controls; a multivariable binary logistic regression of data in the team’s review showed that patients with ATAAs were 298, 250, and 232 times less likely to have an MI than if they had a family history of MI, dyslipidemia, or hypertension, respectively.

Why the Protection?

The ligamentum arteriosum separates the ascending from the descending (thoracoabdominal) aorta. ATAAs, located above the ligamentum, tend to be pro-aneurysmal but anti-atherosclerotic. In the descending aorta, below the ligamentum, atherosclerotic aneurysms develop.

The differences between the two sections of the aorta originate in the germ layer in the embryo, Dr. Elefteriades said. “The fundamental difference in tissue of origin translates into marked differences in the character of aneurysms in the different aortic segments.”

What specifically underlies the reduced cardiovascular risk? “We don’t really know, but we think that there may be two possible etiologies,” Dr. Mukherjee said. One hypothesis involves transforming growth factor–beta (TGF-beta), which is overexpressed in patients with ATAA and seems to increase their vulnerability to aneurysms while also conferring protection from coronary disease risk.

Some studies have shown differences in cellular responses to TGF-beta between the thoracic and abdominal aorta, including collagen production and contractility. Others have shown that some patients who have had an MI have polymorphisms that decrease their levels of TGF-beta.

Furthermore, TGF-beta plays a key role in the development of the intimal layer, which could underpin the lack of intimal thickening in patients with ATAA.

But overall, studies have been mixed and challenging to interpret, Dr. Elefteriades and Dr. Mukherjee agreed. TGF-beta has multiple remodeling roles in the body, and it is difficult at this point to isolate its exact role in aortic disease.

Another hypothesis involves matrix metalloproteinases (MMPs), which are dysregulated in patients with ATAA and may confer some protection, Mukherjee said. Several studies have shown higher plasma levels of certain MMPs in patients with ATAAs. MMPs also were found to be elevated in the thoracic aortic walls of patients with ATAA who had an aortic dissection, as well as in the aortic smooth muscle cells in the intima and media.

In addition, some studies have shown increased levels of MMP-2 in the aortas of patients with ATAAs compared with patients with coronary artery disease.

Adding to the mix of possibilities, “We recently found a gene that’s dysregulated in our aneurysm patients that is very intimately related to atherosclerosis,” Dr. Elefteriades said. “But the work is too preliminary to say anything more at this point.”

“It would be fabulous to prove what it is causing this protection,” Dr. Mukherjee added. “But the truth is we don’t know. These are hypotheses.”

“The most important message from our work is that most clinicians need to dissociate an ATAA from the concept of atherosclerosis,” Dr. Elefteriades said. “The ascending aorta is not an atherosclerotic phenomenon.”

How to Manage Patients With ATAA

What does the distinct character of ATAAs mean for patient management? “Finding a drug to treat ATAAs — to prevent growth, rupture, or dissection — has been like a search for the Holy Grail,” Dr. Elefteriades said. “Statins are not necessary, as this is a non-atherosclerotic process. Although sporadic studies have reported beneficial effects from beta-blockers or angiotensin II receptor blockers (ARBs), this has often been based on ‘soft’ evidence, requiring a combination of outcome measures to achieve significance.”

That said, he noted, “The mainstay, common sense treatment is to keep blood pressure controlled. This is usually achieved by a beta-blocker and an ARB, even if the benefit is not via a direct biologic effect on the aneurysmal degenerative process, but via simple hemodynamics — discouraging rupture by keeping pressure in the aorta low.”

Dr. Mukherjee suggested that these patients should be referred to a specialty aneurysm center where their genes will be evaluated, and then the aneurysm will be followed very closely.

“If the aneurysm is larger than 4.5 cm, we screen the patient every single year, and if they have chest pain, we treat them the same way as we treat other aneurysms,” he said. “As a rule of thumb, if the aneurysm reaches 5 cm, it should come out, although the size at which this should happen may differ between 4.5 cm and 5.5 cm, depending on the patient’s body size.”

As for lifestyle management, Dr. Elefteriades said, “Protection from atherosclerosis and MI won’t go away after the aneurysm is removed. We think it’s in the body’s chemistry. But even though it’s very hard for those patients to have a heart attack, we don’t recommend they eat roast beef every night — although I do think they’d be protected from such lifestyle aberrations.”

For now, he added, “Our team is on a hunt to find a drug to treat ascending disease directly and effectively. We have ongoing laboratory experiments with two drugs undergoing investigation at some level. We hope to embark soon on clinical trials.”

‘A Milestone’

James Hamilton Black III, MD, vice chair of the writing committee for the 2022 American College of Cardiology/American Heart Association Aortic Disease Guideline and chief of Division of Vascular Surgery and Endovascular Therapy at Johns Hopkins Medicine, Baltimore, commented on the review and the concept of ATAA’s atherosclerotic protection.

“The association of ascending aortic aneurysms with a lower risk for MI is an interesting one, but it’s probably influenced, at least in part, by the patient population.” That population is at least partially curated since people are coming to an academic center. In addition, Dr. Black noted, “the patients with ATAAs are younger, and so age may be a confounding factor in the analyses. We wouldn’t expect them to have the same burden of atherosclerosis” as older patients.

Nevertheless, he said, “the findings speak to an emerging body of literature suggesting that although the aorta is a single organ, there are certainly different areas, and these would respond quite differently to environmental or genetic or heritable stressors. This isn’t surprising, and there probably are a lot of factors involved.”

Overall, he said, the findings underscore “the precision medicine approaches we need to take with patients with aortic diseases.”

In a commentary on the team’s review article, published in 2022, John G.T. Augoustides, MD, professor of anesthesiology and critical care at the Perelman School of Medicine in Philadelphia, Pennsylvania, suggested that ATAA’s “silver lining” could advance the understanding of thoracic aortic aneurysm (TAA) management, be integrated with the expanding horizons in hereditary thoracic aortic disease, and might be explored in the context of bicuspid aortic valve disease.

Highlighting the “relative absence” of atherosclerosis in ascending aortic aneurysms and its importance is a “milestone in our understanding,” he concluded. “It is likely that future advances in TAAs will be significantly influenced by this observation.”

Dr. Elefteriades, Dr. Mukherjee, and Dr. Black have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Highlights in diffuse large B-cell lymphoma (DLBCL) from the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition that are particularly relevant to Veterans Health Administration (VHA) patients are reported by Dr Nicholas Burwick of Puget Sound VA Health Care System. 

Dr Burwick begins with a large VHA study examining racial disparities in DLBCL outcomes among veterans. Importantly, overall survival was not significantly different across racial groups.  

He next covers two studies in the DLBCL frontline setting. The first examines the efficacy of standard-dose R-CHOP; reduced-intensity R-CHOP; and an anthracycline alternative regimen among older patients. Standard-dose R-CHOP yielded superior results in patients aged 70- to 79-years but not for those older than 80 years, a group that merits further study. 

The second frontline study focused on the chemotherapy-free regimen mosunetuzumab plus the antibody-drug conjugate polatuzumab vedotin (pola) in patients who are older and unfit for chemotherapy. The combination showed good preliminary efficacy. 

Turning to relapsed/refractory patients, Dr Burwick discusses a real-world study examining response rates to tafasitamab in White vs Black/African American patients and non-Hispanic vs Hispanic patients. Differences between the two groups proved minimal. 

Finally, he discusses a study of the bispecific antibody glofitamab and pola in heavily pretreated patients that showed promising results in this population. 

--

Nicholas R. Burwick, MD, Associate Professor, Department of Medicine, Division of Hematology, University of Washington; Staff Physician, Department of Medicine, Division of Hematology, Puget Sound VA Health Care System, Seattle, Washington  

Nicholas R. Burwick, MD, has disclosed no relevant financial relationships 

Highlights in diffuse large B-cell lymphoma (DLBCL) from the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition that are particularly relevant to Veterans Health Administration (VHA) patients are reported by Dr Nicholas Burwick of Puget Sound VA Health Care System. 

Dr Burwick begins with a large VHA study examining racial disparities in DLBCL outcomes among veterans. Importantly, overall survival was not significantly different across racial groups.  

He next covers two studies in the DLBCL frontline setting. The first examines the efficacy of standard-dose R-CHOP; reduced-intensity R-CHOP; and an anthracycline alternative regimen among older patients. Standard-dose R-CHOP yielded superior results in patients aged 70- to 79-years but not for those older than 80 years, a group that merits further study. 

The second frontline study focused on the chemotherapy-free regimen mosunetuzumab plus the antibody-drug conjugate polatuzumab vedotin (pola) in patients who are older and unfit for chemotherapy. The combination showed good preliminary efficacy. 

Turning to relapsed/refractory patients, Dr Burwick discusses a real-world study examining response rates to tafasitamab in White vs Black/African American patients and non-Hispanic vs Hispanic patients. Differences between the two groups proved minimal. 

Finally, he discusses a study of the bispecific antibody glofitamab and pola in heavily pretreated patients that showed promising results in this population. 

--

Nicholas R. Burwick, MD, Associate Professor, Department of Medicine, Division of Hematology, University of Washington; Staff Physician, Department of Medicine, Division of Hematology, Puget Sound VA Health Care System, Seattle, Washington  

Nicholas R. Burwick, MD, has disclosed no relevant financial relationships 

Highlights in diffuse large B-cell lymphoma (DLBCL) from the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition that are particularly relevant to Veterans Health Administration (VHA) patients are reported by Dr Nicholas Burwick of Puget Sound VA Health Care System. 

Dr Burwick begins with a large VHA study examining racial disparities in DLBCL outcomes among veterans. Importantly, overall survival was not significantly different across racial groups.  

He next covers two studies in the DLBCL frontline setting. The first examines the efficacy of standard-dose R-CHOP; reduced-intensity R-CHOP; and an anthracycline alternative regimen among older patients. Standard-dose R-CHOP yielded superior results in patients aged 70- to 79-years but not for those older than 80 years, a group that merits further study. 

The second frontline study focused on the chemotherapy-free regimen mosunetuzumab plus the antibody-drug conjugate polatuzumab vedotin (pola) in patients who are older and unfit for chemotherapy. The combination showed good preliminary efficacy. 

Turning to relapsed/refractory patients, Dr Burwick discusses a real-world study examining response rates to tafasitamab in White vs Black/African American patients and non-Hispanic vs Hispanic patients. Differences between the two groups proved minimal. 

Finally, he discusses a study of the bispecific antibody glofitamab and pola in heavily pretreated patients that showed promising results in this population. 

--

Nicholas R. Burwick, MD, Associate Professor, Department of Medicine, Division of Hematology, University of Washington; Staff Physician, Department of Medicine, Division of Hematology, Puget Sound VA Health Care System, Seattle, Washington  

Nicholas R. Burwick, MD, has disclosed no relevant financial relationships 

People are surprised when they learn I was an art history major in college. Most folks assume I had majored in biology or chemistry. Their assumption was based on strong odds. The U.S. Bureau of Labor Statistics reports that nearly half of all physicians practicing in this country were biology majors.

I headed off to college clueless about my future. I was hoping to succeed as a walk-on to the football team and beyond that I figured someone or something would guide me toward a career. Had you asked me, “physician” it would have been a definite “Never.”

I flirted with a psychology major, but after a semester I realized that the department was more interested in the behavior of rats rather than humans. I got an “easy A” in the intro to art history and that was the open door I was looking for.

By my senior year I was applying for fellowships to study in faraway places. However, the world situation in 1965 was unsettling for a young man in this country. I had had a strong high school science education and had continued to take a some science courses. Fortunately, I had banked just enough credits so that I could apply to medical school, again without really planning to become a physician.

Even during the sharpest turns in my circuitous path to becoming a small town pediatrician, including a year doing research in exercise physiology in Denmark, I never once regretted my years spent studying art history. I credit them with making me a more sensitive observer.

You can probably understand why I was intrigued by an article I recently read that described a program in which the radiology residents that the Brigham and Women’s Hospital in Boston take a year-long course in art history using the Art Museum at Harvard University as a resource. Titled “Seeing in Art and Medical Imaging,” the program is now 6 years old. Hyewon Hyun, MD, a radiologist and one of its cofounders, observes that “art is the starting point for in-depth conversations about medicine, humanity, and different ways of seeing the world.”

Radiology and dermatology are obviously the two specialties in which the physician relies most heavily on his or her powers of observation. However, every doctor can benefit from learning to really “see” what they are looking at. Looking and seeing are two very different activities. There is obviously the forest-from the-trees phenomenon. Can the physician in a hurried clinical situation muster up the discipline to shift focus back and forth from the lesion or painful body part to the entire patient and beyond? How is the parent responding to the child’s discomfort? How are they dressed? Does this wider view suggest some additional questions to ask that may help you understand how this patient or family will be able to cope with diagnosis or follow up with your treatment plan?

The art historian sees every object in its historical context. What has come before? How have the societal conditions influenced the artist choice of subject and use of materials? How has his or her emotions at the time of creation influenced his or her style? The astute physician must likewise see the patients and their complaints in the broader context of their emotional health and socioeconomic situation. This requires sensitive listening and careful observation.

One doesn’t have to major in art history or spend years roaming through the sometimes dark and dusty halls of the world’s museums to progress from being one who simply looks to a person who really sees the environment and its inhabitants. It is really a state of mind and a commitment to improvement.

As physicians, we often complain or sometimes brag about how many patients we “see” in a day. I fear that too often we mean “looked at.” How frequently did we make the effort to really see the patient?

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

People are surprised when they learn I was an art history major in college. Most folks assume I had majored in biology or chemistry. Their assumption was based on strong odds. The U.S. Bureau of Labor Statistics reports that nearly half of all physicians practicing in this country were biology majors.

I headed off to college clueless about my future. I was hoping to succeed as a walk-on to the football team and beyond that I figured someone or something would guide me toward a career. Had you asked me, “physician” it would have been a definite “Never.”

I flirted with a psychology major, but after a semester I realized that the department was more interested in the behavior of rats rather than humans. I got an “easy A” in the intro to art history and that was the open door I was looking for.

By my senior year I was applying for fellowships to study in faraway places. However, the world situation in 1965 was unsettling for a young man in this country. I had had a strong high school science education and had continued to take a some science courses. Fortunately, I had banked just enough credits so that I could apply to medical school, again without really planning to become a physician.

Even during the sharpest turns in my circuitous path to becoming a small town pediatrician, including a year doing research in exercise physiology in Denmark, I never once regretted my years spent studying art history. I credit them with making me a more sensitive observer.

You can probably understand why I was intrigued by an article I recently read that described a program in which the radiology residents that the Brigham and Women’s Hospital in Boston take a year-long course in art history using the Art Museum at Harvard University as a resource. Titled “Seeing in Art and Medical Imaging,” the program is now 6 years old. Hyewon Hyun, MD, a radiologist and one of its cofounders, observes that “art is the starting point for in-depth conversations about medicine, humanity, and different ways of seeing the world.”

Radiology and dermatology are obviously the two specialties in which the physician relies most heavily on his or her powers of observation. However, every doctor can benefit from learning to really “see” what they are looking at. Looking and seeing are two very different activities. There is obviously the forest-from the-trees phenomenon. Can the physician in a hurried clinical situation muster up the discipline to shift focus back and forth from the lesion or painful body part to the entire patient and beyond? How is the parent responding to the child’s discomfort? How are they dressed? Does this wider view suggest some additional questions to ask that may help you understand how this patient or family will be able to cope with diagnosis or follow up with your treatment plan?

The art historian sees every object in its historical context. What has come before? How have the societal conditions influenced the artist choice of subject and use of materials? How has his or her emotions at the time of creation influenced his or her style? The astute physician must likewise see the patients and their complaints in the broader context of their emotional health and socioeconomic situation. This requires sensitive listening and careful observation.

One doesn’t have to major in art history or spend years roaming through the sometimes dark and dusty halls of the world’s museums to progress from being one who simply looks to a person who really sees the environment and its inhabitants. It is really a state of mind and a commitment to improvement.

As physicians, we often complain or sometimes brag about how many patients we “see” in a day. I fear that too often we mean “looked at.” How frequently did we make the effort to really see the patient?

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

People are surprised when they learn I was an art history major in college. Most folks assume I had majored in biology or chemistry. Their assumption was based on strong odds. The U.S. Bureau of Labor Statistics reports that nearly half of all physicians practicing in this country were biology majors.

I headed off to college clueless about my future. I was hoping to succeed as a walk-on to the football team and beyond that I figured someone or something would guide me toward a career. Had you asked me, “physician” it would have been a definite “Never.”

I flirted with a psychology major, but after a semester I realized that the department was more interested in the behavior of rats rather than humans. I got an “easy A” in the intro to art history and that was the open door I was looking for.

By my senior year I was applying for fellowships to study in faraway places. However, the world situation in 1965 was unsettling for a young man in this country. I had had a strong high school science education and had continued to take a some science courses. Fortunately, I had banked just enough credits so that I could apply to medical school, again without really planning to become a physician.

Even during the sharpest turns in my circuitous path to becoming a small town pediatrician, including a year doing research in exercise physiology in Denmark, I never once regretted my years spent studying art history. I credit them with making me a more sensitive observer.

You can probably understand why I was intrigued by an article I recently read that described a program in which the radiology residents that the Brigham and Women’s Hospital in Boston take a year-long course in art history using the Art Museum at Harvard University as a resource. Titled “Seeing in Art and Medical Imaging,” the program is now 6 years old. Hyewon Hyun, MD, a radiologist and one of its cofounders, observes that “art is the starting point for in-depth conversations about medicine, humanity, and different ways of seeing the world.”

Radiology and dermatology are obviously the two specialties in which the physician relies most heavily on his or her powers of observation. However, every doctor can benefit from learning to really “see” what they are looking at. Looking and seeing are two very different activities. There is obviously the forest-from the-trees phenomenon. Can the physician in a hurried clinical situation muster up the discipline to shift focus back and forth from the lesion or painful body part to the entire patient and beyond? How is the parent responding to the child’s discomfort? How are they dressed? Does this wider view suggest some additional questions to ask that may help you understand how this patient or family will be able to cope with diagnosis or follow up with your treatment plan?

The art historian sees every object in its historical context. What has come before? How have the societal conditions influenced the artist choice of subject and use of materials? How has his or her emotions at the time of creation influenced his or her style? The astute physician must likewise see the patients and their complaints in the broader context of their emotional health and socioeconomic situation. This requires sensitive listening and careful observation.

One doesn’t have to major in art history or spend years roaming through the sometimes dark and dusty halls of the world’s museums to progress from being one who simply looks to a person who really sees the environment and its inhabitants. It is really a state of mind and a commitment to improvement.

As physicians, we often complain or sometimes brag about how many patients we “see” in a day. I fear that too often we mean “looked at.” How frequently did we make the effort to really see the patient?

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Healthcare costs for patients undergoing common surgical procedures are significantly higher when the surgery is performed by a male surgeon rather than a female surgeon, data suggested.

A retrospective, population-based cohort study that included more than 1 million adults undergoing any of 25 common surgical procedures found that total healthcare costs assessed at 1 year following surgery were more than $6000 higher when the surgery was performed by a male surgeon. Costs were also higher at 30 and 90 days for patients treated by male surgeons.

“As a male surgeon, I think our results should cause me and my colleagues to pause and consider why this may be,” said lead author Christopher J. D. Wallis, MD, PhD, assistant professor of surgery at the University of Toronto.

“None of us believe that the presence of a Y chromosome in surgeons means there are worse outcomes, it’s just that generally speaking, men and women, as we have known for decades, practice medicine a little differently. Things like communication style, time they spend with their patients, and even things like guideline adherence are different, and understanding how those differences translate into patient outcomes is the goal of this whole body of work,” said Wallis.

The study was published online November 29 in JAMA Surgery.

Explanation Is Elusive

In earlier work, Dr. Wallis and his team reported that patients treated by female surgeons had a small but statistically significant decrease in 30-day mortality, were less likely to be readmitted to the hospital, and had fewer complications than those treated by male surgeons. In another study, they found worse outcomes among female patients treated by male surgeons.

In the current study, the researchers examined the association between surgeon sex and healthcare costs among patients undergoing various surgical procedures, including coronary artery bypass grafting, appendectomy, hysterectomy, anterior spinal decompression, and knee replacement. They included all adult patients who underwent these procedures at hospitals in Ontario, Canada, between January 2007 and December 2019 in their analysis.

The study sample included 1,165,711 patients. Of this group, 151,054 patients were treated by a female surgeon, and 1,014,657 were treated by a male surgeon.

After adjusting for patient-, surgeon-, anesthesiologist-, and hospital-related factors, they found that 1-year total healthcare costs were $24,882 for patients treated by male surgeons vs $18,517 for patients treated by female surgeons. Healthcare costs were also higher at 30 days (adjusted absolute difference, $3115) and at 90 days (adjusted absolute difference, $4228).

“This translates into a 9%-10% higher risk of costs with male surgeons compared with women surgeons at these time points,” said Dr. Wallis.

“This study cannot provide a specific answer as to why these differences are occurring,” Dr. Wallis said.

“We are currently undertaking more research to better understand the reasons. Our previous studies have shown that patients treated by male physicians have higher rates of death, readmission, and complications. Managing these adverse postoperative events is costly and likely contributes to these differences. Given the size of our study and similar training pathways, we do not think there are technical differences between male and female surgeons. Rather, we are hypothesizing that there may be differences in how physicians practice, make decisions, and consult with patients,” he said.

Ultimately, Dr. Wallis said he would like his research to prompt “a moment of introspection” among his surgical colleagues.

“Hopefully, these data will provide the impetus for further efforts to make surgery, and medicine in general, a field that is welcoming to women,” he said.

Potential Confounding Factors

This study expands the evidence suggesting significant practice differences between male and female surgeons, Ursula Adams, MD, a resident; Caprice C. Greenberg, MD, MPH, chair; and Jared Gallaher, MD, MPH, adjunct assistant professor, all from the Department of Surgery at the University of North Carolina in Chapel Hill, wrote in an accompanying editorial.

They cautioned, however, that “there are many potential confounding factors and possible explanatory mechanisms associated with surgeon sex that make it challenging to untangle influences on costs. Sex may be an easily captured data point, but is understanding the mechanism by which it affects cost the right next step? Surgeons control how and where they practice; they do not have control over their own demographics.”

The editorialists added that while recruiting and retaining women in surgery is important, it is not a solution to controlling costs.

“We must provide surgeons with better data to understand how practice approach and decisions affect cost and support for practice improvement. Only with these insights will we ensure patients of male surgeons receive care that is just as cost-effective as that provided by female surgeons, while also helping to bend the cost curve and improve the quality of surgical care,” they concluded.

‘Admirable’ Data Use

Commenting on the findings, Oluwadamilola “Lola” Fayanju, MD, chief of breast surgery at Penn Medicine in Philadelphia, said, “It is interesting that the study was performed in Canada with its different healthcare system.” Dr. Fayanju did not participate in the study.

“They used administrative data from a national database, and it is admirable that they were able to do that. These data allow us to make large-scale geographical assessments, although they are subject to errors and unmeasured confounders,” said Dr. Fayanju.

Women surgeons may do things that result in better outcomes, she suggested. “In this study, the women were younger and so perhaps were more up to date. They might have optimized management of their patients in the pre-op phase, including better patient selection, which led to better costs. Or in the post-op phase, they might have made themselves readily accessible. For instance, I remove all barriers about getting in touch with me, and I tell my students to make sure the patient can reach you easily,” said Dr. Fayanju.

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care, and the Data Sciences Institute at the University of Toronto. Dr. Wallis, Dr. Adams, Dr. Greenberg, Dr. Gallaher, and Dr. Fayanju reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Healthcare costs for patients undergoing common surgical procedures are significantly higher when the surgery is performed by a male surgeon rather than a female surgeon, data suggested.

A retrospective, population-based cohort study that included more than 1 million adults undergoing any of 25 common surgical procedures found that total healthcare costs assessed at 1 year following surgery were more than $6000 higher when the surgery was performed by a male surgeon. Costs were also higher at 30 and 90 days for patients treated by male surgeons.

“As a male surgeon, I think our results should cause me and my colleagues to pause and consider why this may be,” said lead author Christopher J. D. Wallis, MD, PhD, assistant professor of surgery at the University of Toronto.

“None of us believe that the presence of a Y chromosome in surgeons means there are worse outcomes, it’s just that generally speaking, men and women, as we have known for decades, practice medicine a little differently. Things like communication style, time they spend with their patients, and even things like guideline adherence are different, and understanding how those differences translate into patient outcomes is the goal of this whole body of work,” said Wallis.

The study was published online November 29 in JAMA Surgery.

Explanation Is Elusive

In earlier work, Dr. Wallis and his team reported that patients treated by female surgeons had a small but statistically significant decrease in 30-day mortality, were less likely to be readmitted to the hospital, and had fewer complications than those treated by male surgeons. In another study, they found worse outcomes among female patients treated by male surgeons.

In the current study, the researchers examined the association between surgeon sex and healthcare costs among patients undergoing various surgical procedures, including coronary artery bypass grafting, appendectomy, hysterectomy, anterior spinal decompression, and knee replacement. They included all adult patients who underwent these procedures at hospitals in Ontario, Canada, between January 2007 and December 2019 in their analysis.

The study sample included 1,165,711 patients. Of this group, 151,054 patients were treated by a female surgeon, and 1,014,657 were treated by a male surgeon.

After adjusting for patient-, surgeon-, anesthesiologist-, and hospital-related factors, they found that 1-year total healthcare costs were $24,882 for patients treated by male surgeons vs $18,517 for patients treated by female surgeons. Healthcare costs were also higher at 30 days (adjusted absolute difference, $3115) and at 90 days (adjusted absolute difference, $4228).

“This translates into a 9%-10% higher risk of costs with male surgeons compared with women surgeons at these time points,” said Dr. Wallis.

“This study cannot provide a specific answer as to why these differences are occurring,” Dr. Wallis said.

“We are currently undertaking more research to better understand the reasons. Our previous studies have shown that patients treated by male physicians have higher rates of death, readmission, and complications. Managing these adverse postoperative events is costly and likely contributes to these differences. Given the size of our study and similar training pathways, we do not think there are technical differences between male and female surgeons. Rather, we are hypothesizing that there may be differences in how physicians practice, make decisions, and consult with patients,” he said.

Ultimately, Dr. Wallis said he would like his research to prompt “a moment of introspection” among his surgical colleagues.

“Hopefully, these data will provide the impetus for further efforts to make surgery, and medicine in general, a field that is welcoming to women,” he said.

Potential Confounding Factors

This study expands the evidence suggesting significant practice differences between male and female surgeons, Ursula Adams, MD, a resident; Caprice C. Greenberg, MD, MPH, chair; and Jared Gallaher, MD, MPH, adjunct assistant professor, all from the Department of Surgery at the University of North Carolina in Chapel Hill, wrote in an accompanying editorial.

They cautioned, however, that “there are many potential confounding factors and possible explanatory mechanisms associated with surgeon sex that make it challenging to untangle influences on costs. Sex may be an easily captured data point, but is understanding the mechanism by which it affects cost the right next step? Surgeons control how and where they practice; they do not have control over their own demographics.”

The editorialists added that while recruiting and retaining women in surgery is important, it is not a solution to controlling costs.

“We must provide surgeons with better data to understand how practice approach and decisions affect cost and support for practice improvement. Only with these insights will we ensure patients of male surgeons receive care that is just as cost-effective as that provided by female surgeons, while also helping to bend the cost curve and improve the quality of surgical care,” they concluded.

‘Admirable’ Data Use

Commenting on the findings, Oluwadamilola “Lola” Fayanju, MD, chief of breast surgery at Penn Medicine in Philadelphia, said, “It is interesting that the study was performed in Canada with its different healthcare system.” Dr. Fayanju did not participate in the study.

“They used administrative data from a national database, and it is admirable that they were able to do that. These data allow us to make large-scale geographical assessments, although they are subject to errors and unmeasured confounders,” said Dr. Fayanju.

Women surgeons may do things that result in better outcomes, she suggested. “In this study, the women were younger and so perhaps were more up to date. They might have optimized management of their patients in the pre-op phase, including better patient selection, which led to better costs. Or in the post-op phase, they might have made themselves readily accessible. For instance, I remove all barriers about getting in touch with me, and I tell my students to make sure the patient can reach you easily,” said Dr. Fayanju.

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care, and the Data Sciences Institute at the University of Toronto. Dr. Wallis, Dr. Adams, Dr. Greenberg, Dr. Gallaher, and Dr. Fayanju reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Healthcare costs for patients undergoing common surgical procedures are significantly higher when the surgery is performed by a male surgeon rather than a female surgeon, data suggested.

A retrospective, population-based cohort study that included more than 1 million adults undergoing any of 25 common surgical procedures found that total healthcare costs assessed at 1 year following surgery were more than $6000 higher when the surgery was performed by a male surgeon. Costs were also higher at 30 and 90 days for patients treated by male surgeons.

“As a male surgeon, I think our results should cause me and my colleagues to pause and consider why this may be,” said lead author Christopher J. D. Wallis, MD, PhD, assistant professor of surgery at the University of Toronto.

“None of us believe that the presence of a Y chromosome in surgeons means there are worse outcomes, it’s just that generally speaking, men and women, as we have known for decades, practice medicine a little differently. Things like communication style, time they spend with their patients, and even things like guideline adherence are different, and understanding how those differences translate into patient outcomes is the goal of this whole body of work,” said Wallis.

The study was published online November 29 in JAMA Surgery.

Explanation Is Elusive

In earlier work, Dr. Wallis and his team reported that patients treated by female surgeons had a small but statistically significant decrease in 30-day mortality, were less likely to be readmitted to the hospital, and had fewer complications than those treated by male surgeons. In another study, they found worse outcomes among female patients treated by male surgeons.

In the current study, the researchers examined the association between surgeon sex and healthcare costs among patients undergoing various surgical procedures, including coronary artery bypass grafting, appendectomy, hysterectomy, anterior spinal decompression, and knee replacement. They included all adult patients who underwent these procedures at hospitals in Ontario, Canada, between January 2007 and December 2019 in their analysis.

The study sample included 1,165,711 patients. Of this group, 151,054 patients were treated by a female surgeon, and 1,014,657 were treated by a male surgeon.

After adjusting for patient-, surgeon-, anesthesiologist-, and hospital-related factors, they found that 1-year total healthcare costs were $24,882 for patients treated by male surgeons vs $18,517 for patients treated by female surgeons. Healthcare costs were also higher at 30 days (adjusted absolute difference, $3115) and at 90 days (adjusted absolute difference, $4228).

“This translates into a 9%-10% higher risk of costs with male surgeons compared with women surgeons at these time points,” said Dr. Wallis.

“This study cannot provide a specific answer as to why these differences are occurring,” Dr. Wallis said.

“We are currently undertaking more research to better understand the reasons. Our previous studies have shown that patients treated by male physicians have higher rates of death, readmission, and complications. Managing these adverse postoperative events is costly and likely contributes to these differences. Given the size of our study and similar training pathways, we do not think there are technical differences between male and female surgeons. Rather, we are hypothesizing that there may be differences in how physicians practice, make decisions, and consult with patients,” he said.

Ultimately, Dr. Wallis said he would like his research to prompt “a moment of introspection” among his surgical colleagues.

“Hopefully, these data will provide the impetus for further efforts to make surgery, and medicine in general, a field that is welcoming to women,” he said.

Potential Confounding Factors

This study expands the evidence suggesting significant practice differences between male and female surgeons, Ursula Adams, MD, a resident; Caprice C. Greenberg, MD, MPH, chair; and Jared Gallaher, MD, MPH, adjunct assistant professor, all from the Department of Surgery at the University of North Carolina in Chapel Hill, wrote in an accompanying editorial.

They cautioned, however, that “there are many potential confounding factors and possible explanatory mechanisms associated with surgeon sex that make it challenging to untangle influences on costs. Sex may be an easily captured data point, but is understanding the mechanism by which it affects cost the right next step? Surgeons control how and where they practice; they do not have control over their own demographics.”

The editorialists added that while recruiting and retaining women in surgery is important, it is not a solution to controlling costs.

“We must provide surgeons with better data to understand how practice approach and decisions affect cost and support for practice improvement. Only with these insights will we ensure patients of male surgeons receive care that is just as cost-effective as that provided by female surgeons, while also helping to bend the cost curve and improve the quality of surgical care,” they concluded.

‘Admirable’ Data Use

Commenting on the findings, Oluwadamilola “Lola” Fayanju, MD, chief of breast surgery at Penn Medicine in Philadelphia, said, “It is interesting that the study was performed in Canada with its different healthcare system.” Dr. Fayanju did not participate in the study.

“They used administrative data from a national database, and it is admirable that they were able to do that. These data allow us to make large-scale geographical assessments, although they are subject to errors and unmeasured confounders,” said Dr. Fayanju.

Women surgeons may do things that result in better outcomes, she suggested. “In this study, the women were younger and so perhaps were more up to date. They might have optimized management of their patients in the pre-op phase, including better patient selection, which led to better costs. Or in the post-op phase, they might have made themselves readily accessible. For instance, I remove all barriers about getting in touch with me, and I tell my students to make sure the patient can reach you easily,” said Dr. Fayanju.

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care, and the Data Sciences Institute at the University of Toronto. Dr. Wallis, Dr. Adams, Dr. Greenberg, Dr. Gallaher, and Dr. Fayanju reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Regular moderate to vigorous physical activity predicts larger brain size in key regions, including gray and white matter and the hippocampus, new data suggest. 

METHODOLOGY: 

• The potential neuroprotective effects of regular physical activity on brain structure are unclear despite reported links between physical activity and reduced dementia risk. 
• To investigate, researchers analyzed MRI brain scans from 10,125 healthy adults (mean age, 53 years; 52% male) who self-reported their level of physical activity.
• Moderate to vigorous physical activities, defined as those increasing respiration and pulse rate for at least 10 continuous minutes, was modeled with brain volumes, adjusting for covariates.
• The threshold for defining physically active (vs nonactive) adults was intentionally set at 2.5 days per week, a level far lower than current guidelines.

TAKEAWAY:

• Three quarters of the cohort reported engaging in moderate to vigorous physical activity approximately 4 days per week. 
• Physically active adults tended to be younger, with a higher proportion of White individuals, and with lower rates of hypertension and type 2 diabetes. 
• After adjusting for multiple factors, increased days of moderate to vigorous activity correlated with larger normalized brain volume in multiple regions including total gray matter; white matter; hippocampus; and frontal, parietal, and occipital lobes. 

IN PRACTICE: 

“We found that even moderate levels of physical activity, such as taking fewer than 4,000 steps a day, can have a positive effect on brain health. This is much less than the often-suggested 10,000 steps, making it a more achievable goal for many people,” co-author David Merrill, MD, with Pacific Brain Health Center, Santa Monica, California, said in a statement. 

SOURCE: 

The study, with first author Cyrus A. Raji, MD, PhD, Washington University School of Medicine, St. Louis, was published online in the Journal of Alzheimer’s Disease.

LIMITATIONS: 

Participants self-reported physical activity in the past 2 weeks, which does not reflect a lifetime of activity levels. The correlation identified between physical activity and brain volumes may not be solely attributable to physical activity alone. 

DISCLOSURES: 

The study received funding from several health centers and foundations. Dr. Raji consults for Brainreader ApS, Neurevolution LLC, Apollo Health, Voxelwise Imaging Technology, and Pacific Neuroscience Foundation and is an editorial board member of the Journal of Alzheimer’s Disease but was not involved in the peer-review process.

A version of this article appeared on Medscape.com.

TOPLINE:

Regular moderate to vigorous physical activity predicts larger brain size in key regions, including gray and white matter and the hippocampus, new data suggest. 

METHODOLOGY: 

• The potential neuroprotective effects of regular physical activity on brain structure are unclear despite reported links between physical activity and reduced dementia risk. 
• To investigate, researchers analyzed MRI brain scans from 10,125 healthy adults (mean age, 53 years; 52% male) who self-reported their level of physical activity.
• Moderate to vigorous physical activities, defined as those increasing respiration and pulse rate for at least 10 continuous minutes, was modeled with brain volumes, adjusting for covariates.
• The threshold for defining physically active (vs nonactive) adults was intentionally set at 2.5 days per week, a level far lower than current guidelines.

TAKEAWAY:

• Three quarters of the cohort reported engaging in moderate to vigorous physical activity approximately 4 days per week. 
• Physically active adults tended to be younger, with a higher proportion of White individuals, and with lower rates of hypertension and type 2 diabetes. 
• After adjusting for multiple factors, increased days of moderate to vigorous activity correlated with larger normalized brain volume in multiple regions including total gray matter; white matter; hippocampus; and frontal, parietal, and occipital lobes. 

IN PRACTICE: 

“We found that even moderate levels of physical activity, such as taking fewer than 4,000 steps a day, can have a positive effect on brain health. This is much less than the often-suggested 10,000 steps, making it a more achievable goal for many people,” co-author David Merrill, MD, with Pacific Brain Health Center, Santa Monica, California, said in a statement. 

SOURCE: 

The study, with first author Cyrus A. Raji, MD, PhD, Washington University School of Medicine, St. Louis, was published online in the Journal of Alzheimer’s Disease.

LIMITATIONS: 

Participants self-reported physical activity in the past 2 weeks, which does not reflect a lifetime of activity levels. The correlation identified between physical activity and brain volumes may not be solely attributable to physical activity alone. 

DISCLOSURES: 

The study received funding from several health centers and foundations. Dr. Raji consults for Brainreader ApS, Neurevolution LLC, Apollo Health, Voxelwise Imaging Technology, and Pacific Neuroscience Foundation and is an editorial board member of the Journal of Alzheimer’s Disease but was not involved in the peer-review process.

A version of this article appeared on Medscape.com.

TOPLINE:

Regular moderate to vigorous physical activity predicts larger brain size in key regions, including gray and white matter and the hippocampus, new data suggest. 

METHODOLOGY: 

• The potential neuroprotective effects of regular physical activity on brain structure are unclear despite reported links between physical activity and reduced dementia risk. 
• To investigate, researchers analyzed MRI brain scans from 10,125 healthy adults (mean age, 53 years; 52% male) who self-reported their level of physical activity.
• Moderate to vigorous physical activities, defined as those increasing respiration and pulse rate for at least 10 continuous minutes, was modeled with brain volumes, adjusting for covariates.
• The threshold for defining physically active (vs nonactive) adults was intentionally set at 2.5 days per week, a level far lower than current guidelines.

TAKEAWAY:

• Three quarters of the cohort reported engaging in moderate to vigorous physical activity approximately 4 days per week. 
• Physically active adults tended to be younger, with a higher proportion of White individuals, and with lower rates of hypertension and type 2 diabetes. 
• After adjusting for multiple factors, increased days of moderate to vigorous activity correlated with larger normalized brain volume in multiple regions including total gray matter; white matter; hippocampus; and frontal, parietal, and occipital lobes. 

IN PRACTICE: 

“We found that even moderate levels of physical activity, such as taking fewer than 4,000 steps a day, can have a positive effect on brain health. This is much less than the often-suggested 10,000 steps, making it a more achievable goal for many people,” co-author David Merrill, MD, with Pacific Brain Health Center, Santa Monica, California, said in a statement. 

SOURCE: 

The study, with first author Cyrus A. Raji, MD, PhD, Washington University School of Medicine, St. Louis, was published online in the Journal of Alzheimer’s Disease.

LIMITATIONS: 

Participants self-reported physical activity in the past 2 weeks, which does not reflect a lifetime of activity levels. The correlation identified between physical activity and brain volumes may not be solely attributable to physical activity alone. 

DISCLOSURES: 

The study received funding from several health centers and foundations. Dr. Raji consults for Brainreader ApS, Neurevolution LLC, Apollo Health, Voxelwise Imaging Technology, and Pacific Neuroscience Foundation and is an editorial board member of the Journal of Alzheimer’s Disease but was not involved in the peer-review process.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients aged 50 years or older with clinically apparent Helicobacter pylori infection (CAHPI) have an 11% increased risk for Alzheimer’s disease (AD), results of a large and lengthy population-based study suggest.

METHODOLOGY: 

• Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
• The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
• Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.

TAKEAWAY: 

• Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
• The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
• Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
• The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).

IN PRACTICE:

“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.

SOURCE:

The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.

DISCLOSURES:

The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients aged 50 years or older with clinically apparent Helicobacter pylori infection (CAHPI) have an 11% increased risk for Alzheimer’s disease (AD), results of a large and lengthy population-based study suggest.

METHODOLOGY: 

• Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
• The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
• Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.

TAKEAWAY: 

• Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
• The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
• Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
• The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).

IN PRACTICE:

“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.

SOURCE:

The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.

DISCLOSURES:

The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients aged 50 years or older with clinically apparent Helicobacter pylori infection (CAHPI) have an 11% increased risk for Alzheimer’s disease (AD), results of a large and lengthy population-based study suggest.

METHODOLOGY: 

• Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
• The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
• Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.

TAKEAWAY: 

• Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
• The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
• Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
• The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).

IN PRACTICE:

“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.

SOURCE:

The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.

DISCLOSURES:

The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.